•.r ••• NATIONAL LIBRARY OF MEDICINE NLfl 0D1Q2311 fi 1 \/ ^' ? X V F X "\ 3NI3I03W JO ASVaflll TVNOIIVN 3NOI03W JO AHV89I1 1VNC vW ,' t .W' 1 3f v I X ft NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE ^ " " ^ NATIONAL LIBRARY OF MEDK ,^X^ f /$^I^J> I X" 1 IVNOIIVN ■# X 3Ni3ia3w jo Aavaan ivnoiivn X | X>XU \ ? * "~?X E "i Xx p- 3 y \ /■v v. Jrr-' "J-f3—/ S, 3NIDI03W JO ASVa8IT IVNOIIVN 3NIDI03W jo Aavaaii "IVNO \ aan tvnoii\ jNiDiaaw jo AMvagn ivnoiivn >. ,^pv s A9b X -8 xXS^X 1 X75X %^ 1 V If £ %X * # national library of medicine national library of MEDIC M^i,/ 2 < jc^si, J jj^^y e xx|P 3NIDI03W JO AMVSan IVNOIIVN 3NIDI03W JO AaV89n 1VNO / i X X- I X X i 8 ✓ yr& s ^ \ 8 ✓ X^ 8 /\ wevj^^. )<% X s / * f > j. \.p i x>f :.7 3 '/£*:■' "A ' a4% * /X&^,.V I X-. rM yJ. i. Vw i "If. . TIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL ^y i x^P: i .--^x * /^& 1 "*"' y o ^. ^^ v^X / "* N :') iDia3w jo Aavaan t v x X . X^'V f xf DUE ^X " f < ' Xk f x ■ " FEB 1 0 1971 UIONAL LIBRARY OF ' -*X - X rsx MAR i ^ 17 1971 loroaw jo Aavaan o f ✓ 7 X51' i Xk S@4$& LAST DATE \TIONAL LIBRARY Of .avaan tvnouvn 3NOia3w ° XWx# -§ xxIp; I xllp I S# \RY OF MEDICINE NATIONAL >x Aavaan tvnouvn 3nidio3w SMiX I 'xfT i X-- RARY OF MEDICINE NATIONAL loiasw jo Aavaj V. X o. ■ofx s" xVr V ' X^ ^ TIONAL LIBRARY C ^V>§ D Aavaan ivnoiivn 3NiDirj3w 8- X(esX# slXx ? X •^ BRARY OF MEDICINE NATIONAL ? AvP^ ? yK'^\ v % •-;- ^ , i ,X. J \X loioaw jo Aavaan tvnouvn aNiDiaaw i0 Aavaan tvnouvn 3Nma3w jo Aavaan tvnouvn snidiqsw y\ s A.R f •,.. ^ s AV ? -^ A XiXiXfXX ^K E ,^xi JAX 1" VI^ ± ?"x^ r \^X' * ^^ |- -^ NONAl LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL X \ I X i .X- X^ * l^y / I ' - x= XV ; CYCLOPAEDIA OF THE PRACTICE OF MEDICINE Edited by Dr. H. von- /^EMSSEN, PBOFESSOB OF CLINICAL MEDICINE IN MUNICH, BAVARIA. VOL. XVIL GENERAL ANOMALIES OF NUTRITION, AND POISONS. X BY Prof. H. IMMERMANN, of Basel; Prof. R. BOEHM, of Dorpat; Prof. B. NAUNYN, of Koenigsberg; and Prof. H. von BOECK, of Munich. &ranslat«& ij W. BATHURST WOODMAN, M.D., and J. BURNEY YEO, M.D., of London; EDWARD S. WOOD, M.D., of Boston; CHARLES EMERSON, of Concord; PORTER FARLEY, M.D., of Rochester; and A. BRAYTON BALL, M.D., and ELWYN WALLER, Ph.D., of New York. xx' \s ALBERT H. BUCK, M.D., New York, f/ \b EDITOR OF AMERICAN EDITION. NEW YORK: WILLIAM WOOD AND COMPANY, 27 GREAT JONES STREET. 1878. UX-* \.&Y Z&5c 18"-1 v. n Entered according to Act of Congress, in the year 1878, by WILLIAM WOOD & CO., In the Office of the Librarian of Congress, at Washington. ALL RIGHTS RESERVED. Trow's Printing and Bookbinding Company, 205 to 213 East Twelfth Street, NEW YORK. BIOGRAPHICAL SKETCHES OF THE AUTHORS. Bernhard Naunyn was born in Berlin on the second day of September, 1839, and received his education partly in that city, partly in Bonn. While a student, his duties as an amanuensis, first of Prof. Reichert, afterwards of Prof. Frerichs, afforded him an early opportunity of familiarizing himself with both anatomy and internal medicine. From 1863 to 1868 he was an assistant in the Medical Clinic at Berlin (service of Prof. Frerichs). In 1869 he was invited to fill the position of Professor of the Medical Clinic at Dorpat. In 1871 he was called to fill the same position in Berne, Switzerland. Finally in 1872 he accepted a similar call from the University of Konigsberg, in Prussia. Naunyn's first published works related to questions of anatomy. Thus, his doc- torial thesis was " On the Development of the Echinococcus," and in 1866 he pub- lished a paper " On the Development of Cancers of the Liver." Since 1863, when he became an assistant in Frerichs' Clinic, his chief interest has centred in questions of physiological chemistry and experimental pathology. In the former department he has published the following papers: " On the Chemistry of Transudations and Pus;" "On the Behavior of Carburetted Hydrogen in the Organism." In the department of general pathology, he has made exhaustive studies on the subjects of Icterus, Fever, and Diabetes. Upon the first-named topic he has written two papers, while upon the second he has written four, two of which, however, were published as coming from him and Quincke conjointly (" On the Influence of the Central Nervous System upon the Generation of Heat"), and one from him and Dobrzansky conjointly (" Contribution to the Theory of Rise of Temperature in Fever "). All three of these were published in 1873. In a paper written by him in 1875 on Dia- betes (" Contribution to the Theory of Diabetes Mellitus "), Naunyn has incorpo- rated not only the results of his own investigations upon this question, but also • those of his pupils. Finally, two other works remain still to be mentioned, viz., one published by Francken and himself in 1873, " On the Coagulation of Blood in the Living Animal," and a second by Eichhorst and himself in 1874, "On Degen- eration and Regeneration of the Spinal Cord." The articles which he published before 1873 will all be found in the Archives of Reichert and Dubois, while the later ones have appeared in the " Archiv fur Experimentelle Pathologie, etc.," published by Klebs and Schmiedeberg in con- junction with Naunyn. iv BIOGRAPHICAL SKETCHES OF THE AUTHORS. Rudolf Boehm, the oldest son of the late Dr. Martin Boehm, was born in Nord- lingen, Bavaria, on the 19th of May, 1844. After completing his studies at the gymnasium, he visited first the University of Munich, then that of Wiirzburg, in which latter he took the degree of doctor during the summer of 1867. His univer- sity studies were interrupted in 1866 by the outbreak of the war, and for a time he served as an assistant surgeon in the military hospital at Munich. From the winter of 1866 to the spring of 1868 Boehm devoted his time chiefly, under the direction of F. von Recklinghausen, to pathological and pathologico-anatomical researches, the results of which are incorporated in the following publications, which are his maiden efforts: " Contribution to the Normal and Pathological Anatomy of the Joints" (Dissertation. Wiirzburg, 1868); "Experimental Studies on the Dura Mater of Man and of Mammals" (Virchow's Archiv. Bd. 47. p. 218 ff.). In the spring of 1868 Boehm was appointed an assistant in the Psychiatric Clinic of the Julius Hospital in Wiirzburg, and served in this capacity till the spring of 1870. The duties of this position gave him ample opportunities of becoming familiar with practical medicine, for in addition to his labors in the wards of the insane, he was obliged to prescribe for .the patients in the very large department devoted to epileptics, and also in the so-called "Pfrunde." It was during this period that he published a German edition of Maudsley's " Physiology and Pathol- ogy of the Mind" (Wiirzburg: Stuber, 1870). In the spring of 1870, after completing his service in the Julius Hospital, Boehm went to Leipzig in order to continue his researches in experimental physiology under the direction of Prof. Ludwig. Already in the following summer, however, the breaking out of the Franco-Prussian war compelled him to abandon his scien- tific studies. He took part in the campaign as battalion surgeon of Bavarian troops, and did not resume his work in Leipzig until April, 1871. In the follow- ing autumn he established himself as a " Privatdocent" in the University of Wiirz- burg, his " Habilitation" thesis being entitled " Studies on Heart-Poisons" (Wiirz- burg: Stuber, 1871). He began to deliver lectures during the winter semester of 1871-72, and at the same time acted in the capacity of assistant to Prof. A. Fick, in the Physiological Institute of the Wtlrzburger Hochschule. The following articles were published by him during this period : " Experimental Investigations on the Effects of Digitalis and Digitalin " (Pfluger's Archiv, Bd. V.): (conjointly with A. Hartmann, of Gsneva) " Investigations on the Physiological Effects of the Garman Aconitin" (Verhandlungen der Wiirzburger medicinisch-physikalischen Gesellschaft, 1872) ; " On the Influence of Arsenic Acid on the Unformed Ferments " (Ibid.), etc. In the summer of 1872 Boehm was called to the University of Dorpat, to fill the chair of Materia Medica, Dietetics, and History of Medicine, which had been left vacant by Prof. Schmiedeberg. He accepted the call, and in the following autumn moved to Dorpat, where he has remained up to the present time. As Director of the Pharmacological Institute of the Dorpater Hochschule, Boehm has published in the Archiv fur experimentelle Pathologie und Pharmakologie the following experimental pharmacodynamic and toxicological articles, based either upon BIOGRAPHICAL SKETCHES OF THE AUTHORS. V his own researches or upon those which his pupils have carried out under his direc- tion : 1. On the Effects of Pseudaconitin (Nepalin). Archiv fiir exper. Path, und Pharm. Bd. I. 1872. 2. On the Effects of Arsenic Acid. Ibidem. Bd. II. 1873. 3. On the Influence of Arsenic Acid upon Yeast Fermentation, etc. Ibid. II. 1873. 4. On Nativelle's Preparations of Digitalis. Ibid. II. 1873. 5. On the Effects of Prussic Acid, etc. Ibid. III. 1874. 6. On the Effects of the Salts of Ammonia. Ibid. IV. 1874. 7. On the Effects of the Salts of Baryta. Ibid. V. 1875. 8. On the Nervus Accelerator Cordis of the Cat. Ibid. V. 1875. 9. On Paradoxical Effects produced by the Vagus; a Contribution to the Know- ledge of the Effects of Curare. Ibid. V. 1875. 10. On the Poisonous Constituent of the Water-Hemlock (Cicuta Virosa) and its Effects. Ibid. VI. 1876. 11. Contribution to the Pharmacology and Toxicology of the Preparations of Iodine. Ibid. VI. 1876. 12. The Poisonous Alkaloids of the Seeds of Stavesacre (Delphinium Staphy- sagria). Ibid. VI. 1876. 13. On Restoration to Life after Poisonings and after Asphyxia. Ibid. 1877. Recently Boehm has published, conjointly with the clinicist F. A. Hoffmann, "Contributions to the Physiology of the Changes which Carburetted Hydrogen undergoes" (Archiv fur exp. Pathol. Bd. VIII. 1878). Hermann von Boeck was born on the fourteenth of August, 1843, in a small village of the Bavarian district of Allgau. His father was the practising physician of the place. At the age of ten, von Boeck was sent from home to a school in Bre- genz, on the Lake of Constance. In 1855 he entered the St. Stephen's Gymnasium in Augsburg, and in 1860 the Gymnasium of Munich, where in 1863 he completed his preliminary education. During the following three years he pursued his medi- cal studies at the University of Munich. When the war broke out in 1866, he entered the army as an assistant surgeon, and served in the campaign against the Prussians. Upon the termination of the war in the autumn of 1866, he was appoined an assistant of Prof, von Lindwurm, in the Munich Hospital, and served in this capacity till the early part of 1870. In 1868 and 1869 he passed both the university and the State examinations. In 1870 he continued his studies in Berlin and in Vienna, and in the autumn of the same year began the practice of medicine in Munich. In 1871 he established himself in the university as a "Privatdocent" in Pharmacology. In 1876 he was appointed "Extraordinary Professor" of Materia Medica, Toxicology, etc.—a position which he still holds. Von Boeck's principal literary works are the following: " On the Cold Water Treatment of Typhus." Bayer, aerztliches Intelligenzblatt. 1870. vi BIOGRAPHICAL SKETCHES OF THE AUTHORS. " Investigations on the Decomposition of Albumen in the Human Being under the Influence of Mercury and Iodine." Munich, 1869. Zeitschrift fiir Biologie, von Pettenkofer, Voit, et al. 8. p. 17. " Investigations on the Manner in which Albumen becomes decomposed in the Bodies of Animals under the Influence of Morphine, Quinine, and Arsenic Acid." Munich, 1871. M. Rieger'sche Buchhandlung. 8. p. 52. " Investigations on the Interchange of Gases in the Bodies of Animals under the Influence of certain Remedies." Zeitschrift fiir Biologie. 1875. " On the Effects of Arsenic upon the Tissue-Changes." Zeitschrift fiir Biologie. 1876; and Centralblatt fiir die medicinischen Wissenschafteu von Rosenthal and Senator. 1877. EDITOR'S NOTE. In the Table of Contents of volume XVI., Dr. E. Buchanan Baxter is credited with the translation of the chapters on Anaemia, Chlorosis, Progressive Pernicious Anaemia, and Corpulence. The translation of the latter chapter, however, should have been credited to Dr. John Todhunter, of Dublin. CONTENTS. IMMERMANN. PAGB HEMOPHILIA............................................................... 3 Bibliography................................................... 3 History............................................................ 5 Definition.......................................................... 13 Etiology................................................................ 15 Description of the disease and symptomatology............................ 38 External hemorrhages............................................... 39 Interstitial bleedings................................................ 46 Anatomical changes................................................ 52 Complications and sequelse.......................................... 55 Nature and pathogenesis............................................. 60 Diagnosis........................................................... 78 Duration and terminations........................................... 82 Prognosis.......................................................... 86 Treatment.............................................................. 88 Scurvy.................................................................... 105 Bibliography.................................................... 105 History............................................................. 107 Definition.......................................................... 119 Etiology................................................................ 120 (Translated by A. Brayton Ball, M.D.) Description of the disease................................................ 143 Anatomical changes................................................. 166 Analysis of symptoms.................................................... 177 Nature and pathogenesis............................................. 192 Complications and sequelse........................................... 201 Diagnosis........................................................... 207 Duration, terminations, prognosis.................................... 212 Treatment............................................................. 216 (Translated by Charles Emerson.) yiii CONTENTS. PAGB Morbus Maculosus Werlhofii............................................ 243 Bibliography.................................................... 243 Definition..........................................................243 Etiology................................................................ 249 General features of the disease........................................... 251 Anatomical changes................................................. 256 Analysis of symptoms................................................... 259 Nature and pathogenesis............................................. 265 Complications and sequelae........................................... 269 Diagnosis........................................................... 270 Duration, terminations, prognosis................................... 275 Treatment.............................................................276 (Translated by Porter Farley, M.D.) BOEHM. POISONING BY METALLOIDS................................................. 285 Poisoning by Chlorine................................................... 285 Poisoning by Iodine..................................................... 290 Poisoning by Bromine................................................... 306 Poisoning by Mineral Acids.............................................. 322 Poisoning by Sulphuric Acid.............................................322 Poisoning by Hydrochloric Acid...........................................337 Poisoning by Sulphurous Acid ........................................... 344 Poisoning by Vegetable Acids............................................ 346 Poisoning by Acetic Acid.................................................346 Poisoning by Tartaric and Citric Acids....................................351 Poisoning by Oxalic Acid................................................. 351 Poisoning by Alkalies, Earths, and their Salts........................ 355 Poisoning by Ammonia and Sal Ammoniac................................355 Poisoning by Caustic and Carbonated Alkalies............................. 366 Poisoning by Salts of the Alkalies and Earths.............................. 370 Poisoning by Barium Compounds......................................... 375 Poisoning by Alum...................................................... 379 (Translated by Elwyn Waller, Ph.D.) Poisoning by Anesthetics and other Poisonous Carbon Compounds.....382 Poisoning by Alcohol.................................................... 382 Poisoning by Chloroform......................................... ......416 Poisoning by Ether...................................................... 439 Poisoning by Chloral Hydrate............................................ 445 Poisoning by Amylene..........................i........................ 453 CONTENTS. IX PATH Poisoning by Bichloride of Methylene..................................... 453 Poisoning by Ethylidine..................................................454 Poisoning by Nitrous Oxide.............................................. 454 Poisoning by Carbonic Oxide.........................................___456 Poisoning by Carbonic Acid..............................................472 Poisoning by Bisulphide of Carbon....................................... 477 Poisoning by Sulphuretted Hydrogen..................................... 484 Poisoning by Prussic Acid and Allied Substances........................... 498 Poisoning by Benzin .................................................... 512 Poisoning by Nitro-Benzin............................................... 513 Poisoning by Anilin and Anilin Dyes...................................... 519 Poisoning by Carbolic Acid............................................... 524 Poisoning by Nitro-Glycerine.............................................533 Poisoning by tainted Articles of Diet.................................... 535 Sausage-poisoning.......................................................535 Poisonous Fish..........................................................547 Poisonous Cheese......................................;.................551 (Translated by W. Bathurst Woodman, M.D.) NAUNYN. Poisoning by TnE Heavy Metals and their Salts, including Arsenic and Phos- phorus .................................................................... 557 Lead-poisoning......................................................... 557 Bibliography........................................ .......557 Detection of the compounds of lead in the animal fluids and tissues.. 558 Acute lead-poisoning................................................. 558 Chronic lead-poisoning...............................................560 General description of chronic lead-poisoning...................... 565 Treatment of lead-poisoning in general................................568 Lead colic....................................................... 570 Arthralgia saturnina.............................................574 Lead paralysis.................................................. 576 Encephalopathia saturnina....................................... 581 Theory of the action of lead and lead-poisoning..................... 583 Copper-poisoning........................................................589 Bibliography................................................589 Acute copper-poisoning...............................................590 Chronic copper-poisoning............................................. 592 Zinc- and cadmium-poisoning............................................ 594 Bibliography................................................ 594 Acute zinc-poisoning.................................................595 Chronic zinc-poisoning............................................... 597 CONTEXTS. PAGE Silver-poisoning..........................................................5" Bibliography................................................599 Acute and chronic poisoning..........................................599 Treatment..........................................................601 Mercurial poisoning...................................................... "01 Bibliography................................................. 601 The corrosive action of mercurial preparations upon the intestinal tract 603 Mercurial poisoning by absorption of the poison into the circulation; constitutional mercurial poisoning............................... 605 Treatment.......................................................... 617 Antimony-poisoning..................................................... "19 Bibliography................................................619 General description..............................................62± Treatment.......................................................... 624 Poisoning by salts of Iron................................................ 624 Poisoning by Manganese.................................................. 626 Poisoning by preparations of Chromium.................................... 626 Poisoning by compounds of Tar........................................... 627 Poisoning by Subnitrate of Bismuth....................................... 628 Poisoning by compounds of Gold.......................................... 628 Poisoning by Thallium................................................... 628 Poisoning by Osmic Acid................................................. 629 Phosphorus-poisoning.................................................... 629 Bibliography................................................ 629 Acute phosphorus-poisoning......................................... 631 Treatment.......................................................... 641 Chronic phosphorus-poisoning......................................... 642 Poisoning by Arsenic and Arseniuretted Hydrogen.......................... 644 Bibliography................................................ 644 Acute arsenic-poisoning..............................................648 Chronic arsenic-poisoning............................................652 (Translated by Edward S. Wood, M.D.) VON BOECK. Vegetable Poisons........................................................ 661 Poisoning with Atropine.................................................. 661 Etiology........................................................661 Nature and course of the illness................................... 665 Analysis of symptoms...........................................671 Diagnosis....................................................... 678 Treatment.......................................................... 680 Changes which atropine undergoes in the bodies of men and animals; and tests for atropine.......................................... 686 Poisoning with Hyoscyamus..............................................688 CONTENTS. Xi PAGE Solanine-poisoning....................................................... 689 Symptoms and course...........................................690 Diagnosis and prognosis.......................................... 694 Treatment..........................................................695 Changes which Solanine undergoes in the bodies of animals, and chemical tests................................................. 695 Poisoning by Physostigmine.............................................. 695 Etiology........................................................696 Symptoms and course............................................ 697 Diagnosis and prognosis.......................................... 704 Treatment..........................................................704 Changes which Physostigmine undergoes in the bodies of animals, and tests.......................................................... 705 Poisoning by Digitalis.................................................... 706 Etiology........................................................ 708 Symptoms and course............................................ 709 Diagnosis and prognosis.......................................... 718 Treatment..........................................................719 Changes which Digitalis undergoes in the organism, and tests........ 720 Poisoning by Veratrine................................................... 722 Etiology........................................................723 Symptoms and course............................................724 Diagnosis....................................................... 730 Prognosis....................................................... 731 Treatment..........................................................731 Changes which Veratrine undergoes in the system.................. 731 Chemical tests..................................................732 Poisoning with Colchicine................................................734 Etiology........................................................ 734 Symptoms and course............................................735 Diagnosis.......................................................737 Prognosis.......................................................738 Treatment.......................................................... 739 Changes which Colchicine undergoes in the bodies of animals........ 739 Chemical tests.................................................. 740 Poisoning with Helleborin and Helleborein.................................741 Symptoms......................................................742 Poisoning with Aconitine........................,........................744 Etiology........................................................ 745 Symptoms and course............................................ 747 Diagnosis....................................................... 753 Prognosis....................................................... 754 Treatment.,........................................................ 754 Changes which Aconitine undergoes in the bodies of animals, and chemical tests................................................. 755 xii CONTENTS. PAGK Poisoning with Delphinine..............................'.................. "°' Poisoning with Nicotine.................................................. "59 Etiology........................................................760 Symptoms and course............................................ 764 Diagnosis....................................................... '71 Prognosis....................................................... 772 Treatment.......................................................... 772 Changes which Nicotine undergoes in the organism.................773 Chemical tests.................................................. 774 Poisoning with Strychnine............................................... 775 Etiology....................................................... 776 Symptoms and course............................................ 780 Diagnosis....................................................... 791 Prognosis....................................................... 793 Treatment.......................................................... 794 Changes which Strychnine undergoes in the organism............... 806 Chemical tests..................................................807 Poisoning with Brucine.................................................. 810 Poisoning with Picrotoxin................................................ 810 Etiology........................................................810 Diagnosis and prognosis.......................................... 812 Treatment.......................................................... 813 Changes which the poison undergoes in the organism, and chemical tests......................................................... 813 Poisoning with Confine................................................... 814 Etiology........................................................814 Symptoms and course............................................ 815 Diagnosis and prognosis.......................................... 819 Treatment......................................................... 820 Changes which Confine undergoes in the system, and chemical tests.. 820 Poisoning with Cytisine.................................................. 821 Etiology........................................................ 822 Symptoms and course............................................ 823 Diagnosis.......................................................825 Prognosis...................................................... 826 Treatment..........................................................826 Changes which cytisine undergoes in the organism.................. 827 Poisoning with Cicuta Virosa, Gilnanthe Crocata. and iEthusa Cynapium...... 827 Poisoning with Curarine.................................................829 Etiology........................................................ 830 Symptoms and course............................................ 831 Diagnosis and prognosis.......................................... 837 Treatment.......................................................... 837 Changes which curare undergoes in the organism................... 838 Chemical tests............................................. 840 CONTENTS. Xiii PAGE Poisoning with Opium and Morphine...................................... 841 Etiology........................................................844 Acute poisoning.....................................................849 Symptoms and course............................................849 Chronic opium- and morphine-poisoning...............................855 Diagnosis and prognosis.......................................... 864 Treatment of acute poisoning......................................... 865 Treatment of chronic poisoning....................................... 875 Changes which opium and morphine undergo in the human organism. 877 Chemical tests..................................................880 Poisoning with Santonin................................................. 882 Etiology........................................................882 Symptoms and course............................................ 883 Diagnosis and prognosis.......................................... 888 Treatment.......................................................... 889 Changes which santonin undergoes in the organism................. 889 Chemical tests.................................................. 890 Poisoning with Ergot....................................................890 Acute poisoning..................................................... 892 Etiology........................................................892 Symptoms......................................................893 Diagnosis and prognosis..........................................902 Treatment.......................................................... 902 Changes which ergot undergoes in the organism, and tests...........903 Chronic poisoning.............................,.....................903 Spasmodic ergotism.................................................. 904 Etiology........................................................ 904 Symptoms and course............................................ 906 Diagnosis....................................................... 910 Prognosis....................................................... 911 Treatment.......................................................... 911 Changes which ergot undergoes in the organism....................912 Tests of chronic ergot-poisoning..................................913 Gangrenous ergotism................................................ 914 Etiology........................................................915 Symptoms and course...........................................915 Diagnosis...................................................... 918 Prognosis.......................................................919 Treatment.......................................................... 919 Poisoning by Poisonous Fungi............................................ 920 Edible Fungi; Mushrooms...........................................921 Disease through decayed fungi................................923 Symptoms and course........................................ 923 Diagnosis...................................................925 Treatment...................................................... 925 xiv CONTENTS. PAG2 Poisonous Fungi; Fly-Fungus, Muscarine............................. 926 Etiology.................................................... 927 Symptoms and course.......................................928 Diagnosis.................................................934 Prognosis................................................... 935 Treatment...................................................... 935 Changes which muscarine undergoes in the bodies of animals, and tests.................................................... 937 Poisoning by Amanita Phalloides seu Venenosa.........................938 Etiology.................................................... 938 Symptoms and course........................................939 Poisoning by Russula Integra and Boletus Luridus...................... 941 Poisoning with the Lower Forms of Fungi............................. 942 (Translated by J. Burney Yeo, M.D.) HEMOPHILIA, SCURVY, and MORBUS MACULOSUS. IMMERMANN. Haemophilia, Hemorrhagic Diathesis. {HcemorrhopMMa, Bleeder-disease, Hemorrhagic Idiosyncrasy.) Literature. Alsaharavi, Liber theoreticae nee non practicae (translated from the Arabic by Paulus Bicius. Augsburg, 1519), fol. 145. cap. 15.— Alexander Benedictus, De omnium a vertice ad plantam morborum signis, causis, etc. Liber XXX. Cap. IV. Basil, 1525.—Ph. Hoechstetter, Observ. medicinal, decades sex, ante has editae, quibus nunc accessere quatuor decades aliae, nunquam editae. Dec. 11. Cas. IX. 1627. (See Virchow's Archiv, Bd. XXVIII. S. 427.)—Banyer, Phil. Transactions. Vol. XLII. 1743. No. 471. p. 268. (See W. Legg, Treatise on Haemophilia. Lond. 1872. p. 22.) Sir W. Fordyce, Fragment, chir. et med. Lond. 1784. p. 46.—Medicinische Ephe- meriden. Chemnitz, 1793. p. 267.—Rave, Beobachtungen und Schliisse aus der praktischen Arzneiwissenschaft. Bd. 2. p. 12. 1798.—Otto, Med. Repository. New York. Vol. 6. 1803. (See also Dictionnaire des sciences mfidicales. Vol. IV. p. 190).—Smith and Coxe, Philadelphia Med. Museum. Vol. 1. p. 284. 1805. —Consbruch, Hufeland's Journal. Bd. 30. Stuck 5. 1810.—Hay, New England Journal of Medicine and Surgery. Boston, 1813. Vol. 11. p. 221.—Buel, Trans- actions of the Physico-Medical Society of New York. Vol. 1. 1817.—Blagden, Med.-Chir. Transactions. Vol. 8. 1817.—Nasse, Horns Archiv. 1820. May and June. p. 385.—Kapp, Sammlung auserlesener Abhandlungen. Bd. 22.—Elsas- ser, Hufeland's Journal. Bd. 58, 59, 67, 72. 1824-1833.— Davis, Edinb. Med. and Surg. Journ. April, 1826.—Keller, Von der erblichen Neigung zu todt- lichen Blutungen. Diss. Wiirzburg, 1824.—Hop/, Die Hamophilie. Diss. Wiirz- burg, 1828.—Rieken, Neue Untersuchungeu in Betreff der erblichen Neigung zu todtlichen Blutungen. Frankfurt, 1829.—Reynel Coates, North Amer. Med. and Surg. Journal. 1828. Vol. VI. p. 45.—Tamme Beth, Specimen med. inaug. exhibens historiam haemorrhagiae insolitae e digitis dextrae manus, etc. Groningen, 1829.—Thai, Acta novae societatis Havniensis, 1829.—Schneider, Rust's Magazin. Bd. 30. Heft 3. 1829.—Schliemann, Diss, de disposit. ad haemorrhagias perniciosas hereditaria. Wirsib. 1831.—Richard, Verhandl. der vereinigten arztlichen Gesellschaft der Schweiz. 1831. Heft 1.—Rueber, De dispos. ad. haemorrh. lethales hereditaria. Berol. 1832.—Grandidier, De dis- posit. ad haemorrh. lethales hereditaria. Casselis, 1832.—Idem, Allgemeine Zei- 4 IMMERMANN.—HAEMOPHILIA. tung. 1837. Nr. 20.— Idem, Hclscher's Annalen. Bd. IV. 1839.— Idem, Die Hainophilie oder die Bluterkrankheit. Leipzig, 1855.—Idem, Schmidt's Jahr- biicher. Bd. CXVII. p. 329 sq.—Idem, ibidem. Bd. CLIV. p. 81 sq.—Idem, ibidem. Bd. CLVII. p. 35 sq.—Hey/elder, Med. Vereinszeitung. 1833. Nr. 48.— Fraenzel, Ibidem. Nr. 38.—Roux, Journ. de inedecine et de chirurgie pratique. 1833. Vol. 8.—Hughes, Americ. Journal of the Medical Sciences. 1833. February.—Osborne, Dubl. Journal of Med. Scienc. 1835. March.—Escherich, Wiirttemberg. Correspondenzblatt, Bd. V. Nr. 19.—Kuhl, Opuscula medica, quaestiones chirurg. Pars XIII. 1834.—Roesch, Untersuchungen aus dem Gebiete der Heilwissenschaft. Bd. I. p. 249. 1837.—Biching, Hufeland's Jour- nal. 1837. Heft 4.—La/argue, Revue medicale. Oct. 1835.—Lebert, Archives generates de m6decine. Sept. 1837. — Liston, The Lancet. 1839. April.— Kendrick, Lond. Med. Gazette. 1830. p. 788.—Mende, Mittheilungen aus dem Archive praktischer Aerzte in Riga. 1. Sammlung. 1839.—Gabriel, De haemor- rhagia hereditaria. Ber. 1830.—Lane, The Lancet. Oct. 1840.—Burns, Ibidem. Dec. 1840.— Wilson, Ibid. Oct. 1840.—Mutzenbecher, Dissertatio de haemor- rhagicis.—Heidelb. 1841.—Johannsen, Diss, de haemorrhophilia. Kil. 1842.— Tardieu, Arch, gengrales de m£decine. Sept. 1841.— Wilmot, Lond. Med. Review. 1841. No. 69.— Cochrane, The Lancet. 1842. April, p. 147.—Duncan, Ibidem. 1842. No. 974.—Allan, Monthly Journal. 1842. June.—Steiner, Diss. de haemophilia. Berol. 1842.—Dequevauviller, Journal de chirurgie. June, 1844. — Erdmann, Diss, de haemophilia. Hal. 1744.—Schulz, Diss, de idiosyn- crasia haemorrhag. Berol. 1844.—Pluemicke, Diss, de haemorrhagiis heredi- tarily Berol. 1845.—Clay, The Medic. Times. 1846.— Vieli, Journal de mede- cine et de chirurgie pratique. Aug. 1846.—Lange, Med. Vereinszeitung. 1846. Nr. 6.—Kuster, Caspar's Wochenschrift. 1847. Nr. 18.—Jungken, Deutsche Klinik. 1849. Nr. 5.— JJhde, Ibidem. 1850. Nr. 49.— Wachsmuth, Die Bluter- krankheit. Magdeburg, 1849. (Pamphlet reprinted from Zeitschrift des deut- schen Chirurgenvereins. Bd. III.)—Dubois, Archiv. general, de mMecine. Oct. 1849.— Lange, Oppenheim's Zeitschrift f. d. gesammte Medicin. 1850. October.—Stober, Ueber Ilamophilie. Diss. Erlangen. 1850.—Bowditch, Americ. Journal. 1850. No. 37.—Meinel, Jenaische Annalen. 1851. Bd. II. S. 293.—E. Martin, Ibidem, p. 307.—Fournier, Gazette des hopitaux. 1851. No. 123.— Vir- chow, Handbuch der spec. Pathologie und Therapie. Bd. I. (1854). p. 263 sq. —Zaar, Diss, de haemophilia. Berolin. 1854.—Jacoby, Diss, de haemophilia. 1856.—Huss, Allgemeine med. Centralzeitung. 1856. Nr. 97, $8.—Hyde Salter, Med. Times and Gazette. 1856. March.— Thore, Gazette de Paris. 1856. No. 42.— Vezin, Vierteljahrsschrift f. ger. Msdicin. Bd. VII. p. 336. 1855.— Fischer, Zeitschrift fiir Chir. und Geburtshiilfe. 1. 1855.— Heymann, Virchow's Archiv. Bd. XVI. 1,2. p. 182.—Finger, Oesterreichische Zeitschrift fiir prakt. Heilk. Bd. V. 1859. Beilage—Lemp, De haemophilia nonnulla. Dissert. Bero- lin. 1857.—Schrey, Dissert, de haemophilia. Berol. 1857.— Benavevte, Ann. de la societg de mgdec. d'Anvers. 1861. April,- May.— Victor Resal, Quelques pages sur l'hemophilie. These de Paris. 1861.—Gavoy, These de Strassbourg. HISTORICAL INTRODUCTION. 5 1861.—Lindwurtn, Zeitschrift fur rat. Medicin. 3. R. Bd. XIV. p. 257. 1862. Momberger, Beitrag zur Lehre von der Hemophilic. Inaug.-Diss. Giessen, 1862. Winkler, Dissert, de haemophilia. Berol. 1862.—E. Schmiedt, Ueber die hiiinorrhag. Diathese. Inaug.-Diss. Leipzig, 1863.—Gerken, Diss, de haemo- philia. B^rol. 1863. —Beier, Diss, de haemophilia. Berolin. 1864. — Stro- iwysr, Die chirurgischen Krankheiten des Kopfes. 1864. p. 119.— Otte, Ueber die Bluterkrankheit. Inaug.-Diss. Leipzig, 1865.—G. 0. Weber in Pitha's und Billroth's Handb. der Chir. Bd. I. p. 129. 1865.—Spahn, Drei Falle von Hemo- philic. Inaug.-Diss. Giessen, 1867.—Kbhler, Handbuch der speciellen Patho- logie und Therapie. Bd. I. p. 341. 3. Aufl. 1867.—Schunemann, Virchow's Archiv. Bd. XLI. 1, 2. p. 287. 1867.-7%. Roth, Journal f. Kinderkrankheiten. Bd. LI. p. 9.—St. Vel, TUnion. 1865. No. 110, 111.— Delmas, Journal de Bordeaux. 1868. p. 445.—Assmann, Die Hamophilie. Inaug.-Diss. Berol. 1869. — Ueimrt, Ueber Hamophilie. Inaug.-Diss. Gottingen, 1869.—Cousins, Med. Times and Gazette. Vol. II. 1869.—Heath, Brit. Med. Journal. 1868. Jan. 11. —Durham, Guy's Hospit. Rsports. Vol. XIII. p. 489.—Buss, Med. Times and Gizstte. Nov. 7, 1833. — Wjjinbothim, St. Petersburger med. Zjitschrift. Bd. XVI. p. 112.—R. Parker, Med. Times and Gazette. Dec. 24, 1870. — Traneus, St. Louis Med. and Surgic. Journal. N. S. T. VII. p. 535. 1870.—J. Wickham Legg, Treatise on Haemophilia. London, 1872.—Idem, Med. Times and Gazette. Dec. 2, 1871.—J. Went Walker, Brit, Med. Journal. June 8, 1872.—Charles Brigstock, Ibidem. Aug. 2, 1872.—Grossheim, Deutsche militararztliche Zeit- schrift. Bd. I. 7. S. 319. 1872.— W. Legg, Brit. Med. Journal. February 8, 1873.—Gilntner, Oestreichische Zeitschrift f. prakt. Heilkunde. Bd. XVIII. S. 72.—Holton, American Journal of the Med. Sciences. 1874. p. 84.— Chase, Philadelph. M3d. and Surgical Reporter. 1873. Dec. 5.—Higgens, The Lancet. 1873. May 23. Historical Introduction. The earliest historical mention of true cases of the hemor- rhagic diathesis, which correspond in their habitual and at the same time hereditary character to the "haemophilia" of the present day, is in all probability to be found in a passage in the writings of the Arabian physician, Khalaf Abul Kasim el Zahrewi, known also as Abul Kasim or Alsaharavi, who died at Cordova in a.d. 1107. Although this writer had no knowledge of the affection except what was told him by individuals who were afflicted with the idiosyncrasy, his description is so true in its main outlines to what we now know as the bleeder disease, that one cannot but recognize his account as the first authentic evi- 6 IMMERMANN.—HAEMOPHILIA. dence of the existence of the affection in earlier times, and we therefore give the passage in full as it appears in the barbarous Latin translation by Paulus Hicius (1. c.): De passione fluxus sanguinis a quocumaue locorum. "Vidi in quibusdam regionibus casale quoddam, dictum ' al-kiria,'viros, qui narraverunt mihi, quoniam, cum accidit in corporibus ipsorum vulnus aliquod mag- num, indesinenter fluit sanguis ox vulnere, quousque moritur. Et recitaverunt mihi super hoc, quod quibusdam ex pueris suis, cum fricaret manu gingivas, cepit san- guis fluere ex illis, donee mortuus sit. Alius vero, flebotomatus a minutore sangui- nis, non cessavit ex eo fluere, donee periit. Et universaliter eorum mors, ut in pluribus, contigit in hunc modum. Haec est res, quain nunquam et nusquam vidi, nisi in casale praedicto, nee reperii hoc accidens ab aliquo antiquorum memoran- tium, nee scio ejus causSm, et, quod mihi videtur de curatione ejus, est, quod ille, cui hoc accidit, celeriter cauterizet locum, donee sanguis restringatur, et ego minime probavi hoc, et est apud me monstrum." The above quotation evidently refers to the existence of a disposition in the males of certain families to obstinate and uncontrollable hemorrhages after the reception of injuries—a dis- position quite analogous to that observed in the "bleeders" or "lisemophilists" of our own day. That Alsaharavi was correct in his assertion that none of the older writers had referred to the disease, is shown by the entire failure of modern research to dis- cover any trace of the affection in the works of the Greek, Latin, Arabian, or other ancient authors. Furthermore, in character- izing finally the extraordinary behavior of the individuals in question as something "monstrous," Alsaharavi manifests a feeling from which even more recent times have found it difficult to escape. For, previous to the rediscovery of haemophilia as a special form of' disease about a century ago, a long period elapsed during which persons who were afflicted with this idio- syncrasy would naturally have been looked upon as subjects of " demoniac possession ;" indeed, as Grandidier has well pointed out, it must be regarded as a really fortunate circumstance that hemophilia was in fact almost unknown among the populations of Europe during the entire interval from Alsaharavi (1107) to Fordyce (1784), because otherwise the affection could scarcely have failed to play a very dangerous part in the history of civil- ization during the times of witchcraft and the persecutions attending this delusion. HISTORICAL INTRODUCTION. 7 The symptoms of haemophilia are of such a striking character that it is difficult to explain the almost complete gap in the his- tory of the disease during the latter part of the middle ages, and even in modern times up to the beginning of the eighteenth century, except upon the supposition that cases of this affection were comparatively rare during the whole of this long period. That cases did occur, however, from time to time, is not only intrinsically probable, but is shown by reports of isolated cases, although some of these accounts.are not so complete as might be desired. Thus, Alexander Benedictus, who died in 1525 while professor at Padua, gives an account of the singular death of a Venetian barber, who, while clipping the hairs at the end of his nose, acci- dentally punctured the skin with the point of the scissors, and died from the hemorrhage thus produced (1. a). The passage in question unfortunately does not give us any further information, and is, moreover, somewhat obscurely worded ; but it is difficult in reading it to avoid the suspicion that it really refers to a case of haemophilia. Far more trustworthy is the report of another case, discovered by Virchow in the almost forgotten work of Philipp Hoechstetter (1. c), a practising and hospital physician in Augsburg, who died in 1635 ; the case was republished b}^ Vir- chow (1863) in his Archives (Vol. XXVIII., p. 426). The patient was a boy, who from birth had suffered on all possible occasions from more or less severe attacks of bleeding, such as umbilical hemorrhages during the first days of life, repeated epistaxes, bloody stools and petechial eruptions, and in fact presented in every respect a very well-marked picture of haemophilia. Still another case, reported by Dr. Banyer1 as early as 1743 in Eng- land, has recently (1872) been discovered by Wickham Legg, after having been entirely overlooked for more than a century. The patient, a young man twenty-four years of age, was attacked for the first time in 1729 with a dangerous hemorrhage, after a slight puncture from a rusty nail in the sole of the right foot, and thereafter, up to the time of his death in 1738, continued to 1 Philosophical Transactions, Vol. XLII. 1743. No. 471, p. 268. 8 IMMERMANN.—HAEMOPHILIA. manifest a marked tendency to hemorrhages of the character of haemophilia upon a great variety of occasions. With the exception, however, of these few older reports, our knowledge of haemophilia as a specific form of the hemorrhagic diseases is entirely an acquisition of modern times ; in fact, it cannot be truly said to have commenced until the present cen- tury. To be sure, towards the close of the last century Fordyce (1784) gave an account of a hemorrhagic disposition noticed by him in several individuals belonging to the same family circle— the disposition being therefore probably of an hereditary charac- ter ; and soon afterwards other families of bleeders were reported in Germany (Westphalia) by a writer in the "Medicinischen Ephemeriden," published at Chemnitz (1793), and by Rave (1798). Still, for some years these articles attracted but little attention, and no general interest was excited in Europe until after a series of cases had been reported in American journals. The first of these American articles appeared in the Medical Repository of New York, and contained an account by Otto of a widespread bleeder family, in which the disease could be traced back for nearly a hundred years. Three other bleeder families are re- ferred to, observed by Rush and Boardley. The word " bleeder" was here first used. This epoch-making article was soon fol- lowed by others: one by Coxe and Smith1 (1805), another by Hay (1813) of the large bleeder family Appleton-Brown, and finally, in 1817, another report of a bleeder family by Buel. These cases, in addition to those reported by Fordyce and his immediate German successors, and some other observations published by Consbruch (1. c.) in 1810, now afforded for the first time sufficient material for a systematic description of the disease. 1 This article consists of a letter written by Dr. E. H. Smith, of New York, in 1794, to Dr. Rush, of the same city, in reference to the case of a child who died from hemor- rhage, which had previously recurred a few days before each birthday, and had always stopped upon the birthday. Death occurred five days before his fourth birthday. The case has always been quoted by the Germans as Coxe's or Lowthorp's • but as Wickham ILegg has pointed out in his work on Haemophilia (London, 1872, p. 20), Coxe's only con- nection with the case was an addendum to the letter, quoting two other instances from Lowthorp's Abridgement of the Philosophical Transactions of London, neither of which cases, however, seems to have been an instance of the genuine disease.__Translator's JJote. HISTORICAL INTRODUCTION. 9 This task was undertaken by Nasse, and, considering the imperfect material at his command, his treatment of the subject cannot be too highly praised. In an article published in 1820 (1. c), on "An hereditary disposition to fatal hemorrhages," he quotes all the cases which had been reported since the time of Alsaharavi, and discusses the etiology, symptoms, and termina- tions of the bleeder disease with the same thorough method and classic clearness of style which characterize all of his writings. The article excited everywhere, but especially in Germany, a lively interest in the study of this interesting affection, and was followed between this time and 1850 by numerous publications, many of them inaugural dissertations written at Wiirzburg and Berlin under the influence of the teachings of Schoenlein, who was much interested in the disease, and was the first to give it a permanent position in systematic pathology under the present name " hae- mophilia" (or haemorrhophilia). In other countries also, particu- larly England, North America, and Switzerland, a considerable number of new cases, as well as of families of bleeders, were reported in journal articles and larger treatises ; indeed, this period of thirty years surpassed all others, past or present, in the copiousness of its literature on the subject. Among the German articles we may mention, especially, those by Krimer (1820), Elsaesser (1824-1833), Steinmetz (1828), Rieken (1829), Kuhl (1834), and Grandidier (1832-1839); followed in 1849 by the two articles of Wachsmuth and Lange, which were the most impor- tant and comprehensive that appeared during this period; and in 1851 by the valuable reports of Meinel and Martin, in reference to bleeder families in Franconia and Thuringia. Wachsmuth's article is a true monograph of the disease. It not only shows an intimate acquaintance with the previous literature of the subject, but contains also an account of several cases in his own family circle, and is the best and most complete treatise, with the excep- tion of the earlier article of Nasse and the later ones of Virchow, Grandidier, and Legg; while to Lange we are indebted for the first vigorous prosecution of the statistics of the disease — a branch of the subject attended by immense difficulties. Of the articles which appeared in other countries during this period, the most valuable are those of the American physicians, 10 IMMERMANN. —HAEMOPHILIA. Reynell Coates, Hughes, and Bowditch (11. cc.); in England, the treatises of Blagden, Davis, Murray, Osborne, Kendrick, Lane, Cochrane, Allan, and Clay (11. cc.) ; and in Switzerland, Vieli's interesting reports of the two large bleeder families at Tenna, in Graubiinden, to which we shall have repeated occasion to refer in the present article. The comparative scantiness of the literature on this subject in France, and other countries speaking the Romanic languages, is mainly due to the lack of interest occasioned by the rarity of the disease among the populations of the so-called Latin race. Several important articles, however, by French writers (Roux, Lafargue, Lebert, Dequevauviller, Dubois, etc.), will be found mentioned in the preceding bibliography. Among the more extended articles since 1850, one of the most valuable is the chapter devoted to this affection in Virchow's Manual of Special Patholog}^ (1854, Vol. I. p. 263 et seq.). Brief as it is, this excellent article contains everything of importance on the subject up to that time, and by its clear statement of the causes of the disease, and careful description of its chief symp- toms, gives a true and vivid picture of the affection. In the fol- lowing year (1855) appeared an exhaustive monograph by Gran- didier, who, as we have seen, had already published several shorter communications, and had done good work in promoting the study of the subject by his digests of current literature on haemophilia in Schmidt's Jahrbiicher des gesammten Medicin.1 To these treatises of Grandidier, Virchow, Wachsmuth, and Nasse, more than to any others, we are mainly indebted for our present knowledge, and we shall, therefore, use them freely in our own account of the disease, at the same time urgently recom- mending the reader to consult the articles themselves to supply any deficiencies that may appear here. Of recent publications in other countries, Wickham Legg's work (London, 1872) requires particular mention. It contains several new cases observed by the author, reviews thoroughly the entire previous literature of the disease, and advances some 1 1862, Vol. CXVII. p. 329; and 1872, Vol. CLIV. p. 81. HISTORICAL INTRODUCTION. 11 original opinions characterized by a soundness of judgment which entitles them to careful consideration. The preceding summary must suffice, as it is not the object of this historical introduction to enter fully into the details of the literature of haemophilia. Nor is it desirable to detain the reader with an account of all the theories which have been advanced in explanation of the anomaly since the affection came to be more generally known nearly a century ago. It is only necessary to say that none of them has gained exclusive acceptance, and that this fatal affection still remains one of the "enigmas" of pathology, the solution of which must be left to the future. A few words may be added, however, with respect to the temporal and spatial frequency of the disease. That the affec- tion has gained in frequency to an important degree within a comparatively recent period can scarcely be doubted. As we have already seen, not a trace of haemophilia is to be found any- where in the entire literature of the middle ages and earlier part of modern times, with the exception of the doubtful passage in Alexander Benedictus, and Hoechstetter's case ; and in none of the bleeder families can the disease be followed back further than the beginning of the last century. To be sure, this silence of writers during the period referred to does not necessarily indi- cate the entire absence of the disease in those times; still, as suggested above, some mention of it might naturally be expected if the affection had been frequently observed. Moreover, in con- sequence of the great fecundity of bleeder families, and the marked inheritability of the anomaly, there seems to be every likelihood that the affection will become still more common in the future. The few bleeders existing two hundred years ago have probably by this time a considerable number of bleeder descendants, and this number is likely to steadily increase. Cer- tainly thus far the natural restrictions to the propagation of the disease—the premature death of many members of these families, and the failure of others to beget offspring after attaining the proper age—have failed to check the progress of the affection, not to mention the possibility of its spontaneous extinction. It becomes a question, therefore, whether active precautions, of both a private and public nature, may not perhaps be warrant- 12 IMMERMANN.—HEMOPHILIA. able to prevent the disease ultimately becoming a social calamity; but the full consideration of this inquiry must be deferred to the chapter on Prophylaxis. As to the spatial frequency, or, in other words, the geogra- phical extension of haemophilia, statistics seem to show that the disease occurs more frequently in certain countries and groups of countries than in others, and is therefore not uniformly dis- tributed over the earth's surface. From the more or less uncivil- ized portions of the globe reports of either the existence or non-existence of the disease are naturally wanting; still, even in countries thoroughly penetrated by the scientific spirit, differ- ences as to the frequency of the affection are noticeable, which cannot be attributed to a negligence of medical observation. Thus, in Germany, where, particularly in the Rhine and Main districts, a special industry in the collection of cases was awak- ened by Nasse and Schoenlein, the disease still seems to be exceptionally common, notwithstanding the interest excited else- where. Next to Germany in the order of frequency comes Great Britain, followed by the northern countries Sweden, Nor- way, and Denmark ; then North America, Holland, Belgium, Switzerland, Russia, Poland, and France, while no cases have been reported from Italy, Spain, Portugal, Greece, and Turkey. Upon the whole, therefore, the widespread Anglo-Germanic family of nations in both the Old and New World appears to be affected much more frequently than the populations of the so- called Latin race ; but that the latter, and the Slavic nations also, are not wholly exempt, is shown by reports of several cases in France and Russia; and that, finally, the affection is not confined solely to the so-called Caucasian race, appears from a recent lengthy account by Heymann (1. c.) of a Malayan family of bleeders at Palembang, in Java. It is clear, moreover, from the geographical distribution of the disease, that the prevalence of haemophilia is little or not at all influenced by climatic differ- ences, and the same remark will apply also to the elevation of the regions affected. Cases are reported of bleeders and families of bleeders from the lowlands of Holland and Livland, as well as from the high Alpine valleys of Switzerland (Vieli) ; in fact, wherever the disease has been observed, it has always presented DEFINITION OF THE DISEASE. 13 the same stereotyped form, whatever the external conditions of geographical position or social life. We append a table of the geographical distribution of the disease, comprising the cases compiled by Grandidier up to 1872, together with all the new cases which we have discovered for 1873 and 1874. It shows strikingly the unenviable pre- eminence of the Angio-Germanic race, and particularly of the German nation, in respect to the prevalence of the disease. The table includes 650 authentic cases occurring in 219 families. Of these families there were in Germany........................................... 94 Great Britain....................................... 52 North America...................................... 23 France..........................'................... 22 Russia and Poland.................................. 10 Switzerland........................................ 9 Sweden, Norway, and Denmark....................... 6 Holland and Belgium................................ 2 Java............................................... 1 General Definition of the Disease. As commonly observed, haemophilia or the bleeder disease (haemorrhophilia, hemorrhagic idiosyncrasy) may be defined as a congenital and habitual hemorrhagic diathesis, since the ex- tremely obstinate and dangerous hemorrhages for which bleeders are noted usually begin in the very earliest years of life, and recur liabitually. At all events, it is decidedly exceptional for an habitual hemorrhagic tendency, accompanied by the other clinical peculiarities to be presently described, to originate in middle life, so as to warrant us in regarding the disposition as acquired. On the other hand, it is equally uncommon for an individual who has been a marked bleeder in infancy, and in whom therefore the disposition was presumably congenital, to lose the idiosyncrasy completely in early youth, and remain thereafter entirely free from hemorrhagic attacks. In fact, the congenital origin and the habitual nature of the disposition are so constantly observed together in the so-called bleeders, that although each of these attributes is doubtless important by itself, it is unquestionably their combination that constitutes the chief characteristic of haemophilia. 14 IMMERMANN.—HAEMOPHILIA. For the present we may be permitted to rest with this general definition, leaving for future consideration those exceptional cases of haemophilia in which either the congenital or the habit- ual character of the affection is but slightly marked or entirely absent. As we shall see later, some of these cases, as well as some even quite transitory forms of hemorrhagic diathesis, are clearly entitled by their etiology to be regarded as haemophilia; still, in such a broadening of our conception of the disease, it is evident that these anomalous and rudimentary forms must lack those external characters which are pathognomonic of the bleeder anomaly, and that the diagnosis of such cases, therefore, can never be more than conjectural (see Diagnosis). On the other hand, if we confine ourselves to the usual and well-marked forms of the disease, it will be seen that it is just these two attributes which chiefly distinguish haemophilia from other hemorrhagic affections, particularly scurvy and the mor- bus maculosus Werlhofii (see the two following articles). All of these other forms of hemorrhagic diathesis, especially the two mentioned, present neither of these attributes, but are essen- tially acquired and transitory processes. Haemophilia, on the other hand—at least so far as we can judge from clinical symp- toms—does not appear to be in any true sense a pathological pro- cess or morbid " accident," but rather an abnormal "condition " of the living organism, and probably depends for its material sub- stratum not upon a tissue-change which runs a definite course, but far rather upon an original structural vice (vitium primae formationis). Were such an anatomical basis for the disease actually demonstrated in the form of some abnormity, which we could not but regard as really a so-called " defect of organiza- tion," our difficulties as to the nature and proper definition of haemophilia would naturally end at once, and it would only remain to investigate those exceptional conditions under which the manifestations of the anomaly, instead of appearing at the outset and throughout the course of life, occasionally appear only at a later age, or even only transitorily. Unfortunately, how- ever, it must be confessed that our knowledge of the anatomical nature of the bleeder diathesis is as yet little more than rudimen- ETIOLOGY.—HEREDITARY DISPOSITION. 15 tary, and that for this very reason the affection still belongs to the obscure problems of special pathology. As a strict definition of the nature of the bleeder disease is therefore at present impracticable, these few remarks must suf- fice, little as they really add to our knowledge of the pathologi- cal condition which underlies the disease. In the further consid- eration of our subject, also, the disadvantages of not having a definite established theory of the affection will be equally appar- ent. Thus, in the following chapters on the causes, general pic- ture, and individual symptoms of the disease, it will be impos- sible to treat these topics synthetically in a logically connected manner, and we shall therefore be obliged to content ourselves at first with a mere analysis of the facts as they have been ascer- tained empirically, without attempting any a priori explana- tions either as to the mode of action of the observed causes, or as to the origin of particular symptoms. After these points have been discussed, we shall again take up the question in regard to the nature of the affection—that is, in regard to the internal con- nection between the clinical facts. The results of investigation, as we have already intimated, certainly afford but a very unsat- isfactory answer to the question, and we should be disposed to abstain altogether from any theoretical discussion of the nature and mode of origin of haemophilia, were it not that the didactic character of the present work demands that at least an attempt should be made at a comprehensive deduction of the facts observed. It is this consideration alone, and not the conscious- ness that we have any exhaustive theory of our own to offer, that has led us to devote a short theoretical excursus to the sub- ject later in the article. Etiology. A. Predisposing Causes. 1. Hereditary family disposition. Of all known predispos- ing causes of the bleeder disease, this is unquestionably the most striking and important. Grandidier speaks of the affection 16 IMMERMANN.—HAEMOPHILIA. as altogether " the most hereditary of all hereditary diseases ; " while Nasse, in the very title of his work—" An Hereditary Dis- position to Fatal Hemorrhages "—shows the importance he attri- buted to this characteristic which he was the first to make gener- ally known. In fact, when one case of the disease has occurred in a family, i. e., in a group of blood-relations, other members are almost always affected sooner or later. This cumulation of the affection in certain families becomes readily apparent when we compare the total number of recorded cases with the number of families affected. Such a comparison shows that the number of individual cases is almost three times as large as the number of families ; or, in other words, that haemophilia, when it once manifests itself in a family circle, is rarely content with a single victim. Grandidier's compilation in 1862 included 512 cases distributed among 174 families. By 1872, according to the same writer, these numbers had increased to 631 and 213 respectively. For the years 1873 and 1874 we have discovered 19 more oases reported in medical literature, occurring in 6 families. This gives a total, therefore, of 650 bleeders to 219 families, or nearly three bleeders to every family affected. This cumulation of the affection in certain families — the so-called bleeder families—sometimes takes place more or less rapidly through the birth of a greater or less number of bleeder children in a family where the parents and ancestors have been entirely free from haemophilia; at other times the cumulation develops gradually through a longer period of time, the anom- aly starting in a single individual, and descending directly through a series of successive generations. In the first case we have to deal with what may be termed a multiple congenital ori- gin of haemophilia ; in the latter case with a direct transmission of the disease. Usually, however, when the first mode of cumu- lation has once disclosed itself, the other ultimately becomes associated with it, since the occurrence of several congenital cases in a family is generally followed by a direct transmission of the disease. A third, and at the same time the most impor- tant mode of propagation, is by means of what may be called indirect transmission. Thus, after one or more cases of haemo- philia have appeared among the children of healthy parents, the ETIOLOGY.—HEREDITARY DISPOSITION. 17 affection is usually handed down, not so much by the bleeders themselves, as by their non-bleeder brothers and sisters; and this singular mode of transmission of the outward manifestations of the disease may be repeated for several generations. In such cases, therefore, if we leave out of account the genealogical start- ing-point of the affection, the clinical or non-latent phase of the disease is evidently propagated in its further course along side or indirect paths, and not in the line of direct descent. Now, while the single congenital origin of haemophilia in families hitherto free from the disease merely increases the number of individual cases in equal proportion to the number of bleeder families, it is clear that by the much more common modes of propagation— multiple congenital origin, and direct and indirect transmission —the number of individual cases increases much more rapidly than the number of bleeder families, and that there is therefore good reason to apprehend that the present ratio of three to one, instead of remaining constant, will steadily become larger in the future. If it seems surprising, on the other hand, that the pres- ent ratio is so small, it should be borne in mind that our exact historical knowledge of haemophilia dates back only to the end of the last century, and that no careful statistical studies were made until quite recently—in fact, only since the time of Lange. The main cause, however, for this low ratio, doubtless lies in the operation of certain factors, which tend directly to restrict the multiplication of primitive cases, as well as to prevent the cumula- tion of the disease. The proportion between bleeders and bleeder families must unquestionably, even by this time, have become far larger than it is, if (1) all new members of a bleeder family ■were themselves actually bleeders, and if (2) all bleeders pro- duced offspring ; but, in point of fact, there are important limita- tions in both these particulars. Thus, many of the new members of these circles fail to manifest the disease at all, and while some of these failures are apparently mere irregularities of a com- pletely erratic character, others, as we shall see in the following section, are observed so frequently that they may almost be said to follow a law of the disease. On the other hand, a very large number of actual bleeders die from the disease so early in life (see Terminations) as to be unable to take any share in the VOL. XVII—2 18 IMMERMANN.—HAEMOPHILIA. propagation of the anomaly. Indeed, this great premature mor- tality of bleeders is the main reason—aside from another to be considered under the Sexual Disposition—why the direct hered- itary transmission of haemophilia is much more rare than the indirect; since the non-bleeder brothers and sisters, on account of their freedom from this danger to life, far more commonly attain the procreative age. On the other hand, bleeder families present another peculiar- ity, which, instead of restricting, tends rather to increase the number of cases in these circles, viz., the extraordinary fruit- fulness of the non-bleeder brothers and sisters—a peculiarity, moreover, of great importance in relation to the indirect trans- mission of the disease through these members of the family. Since attention was first called to this remarkable fact by Wachsmuth, the confirmations of it by later observers have become so numerous that it can no longer be regarded as merely accidental. Thus, direct investigation has shown that the average number of legitimate births in bleeder circles is nearly double the ordinary average ; and although some writers have been dis- posed to ascribe a teleological significance to this peculiarity by regarding it as a " remedium naturae" against the excessive mortality of bleeders, it is none the less clear that the interests of society are endangered by a provision—if it be such—which threatens to seriously increase the frequency of this fatal affection. The first statistics on this point were published by Wachsmuth, and embraced only twelve marriages in bleeder families. From these marriages were born 114 children, or 9.5 children to each marriage; whereas the normal average of chil- dren born in wedlock is only about five. A later compilation by Grandidier showed 204 children to 21 bleeder marriages, or a ratio of 9.7 to 1; and a still later estimate 324 children to 36 marriages, or exactly 9 children to each marriage. These figures show, at all events, that the asserted fecundity of bleeder families is in all probability not imaginary, but real, and in some way intimately connected with the nature of the anomaly itself. What makes this peculiarity the more remarkable is the fact that most of the individuals who manifest it are not them- selves bleeders, and yet are able to transmit the disease, the latent anomaly in their own persons appearing fully developed in their children. The terrible importance of haemophilia to the welfare of the ETIOLOGY.—HEREDITARY DISPOSITION. 19 families concerned, on account of its markedly hereditary and dangerous character, would naturally lead us to expect that in many of these families full accounts of the existence of the affec- tion in former generations would have been handed down through oral or even written tradition. In fact, several of these families possess records so complete in this particular that it has been possible to construct an actual family tree of the disease, with roots or main branches running back through several decades or even a century and upwards, and ramifying more or less widely in later times. Thus, in the American bleeder families Smith-Shepard and Appleton-Brown, the disease could be directly traced through the entire interval from 1720 to 1806 (Otto, Hay); while of the two unrelated bleeder families at Tenna in Graubiinden, one at least has been affected since 1770 (Vieli, Grandidier), and in the two families together the affection had gained such headway by the year 1854, that at Tenna alone, out of a total population of 165, there were at that date no less than fifteen bleeders. So also Dr. Schrey, who was himself a bleeder, informs us (Dissert, de haemophilia. 1857. Berolini) that the disease could be traced in the widespread bleeder family to which he belonged in Miihlfurt (Rhenish Prussia) as far back as 1750. Other instances of a similar kind may be found in the statistical compila- tions of Grandidier (11. cc), which show that up to 1872 there were in all 73 care- fully described cases possessing a clear genealogical record of the disease. That the results of investigation upon this point should have been less satisfactory in other cases, which were possibly just as truly of an hereditary character, is certainly not surprising, if we consider how few families are able to recall the pathological fate of their ancestors even when it has been of a peculiar character, and how very readily the rudimentary cases, which occur in bleeder families alongside of the marked forms of the disease, might be overlooked entirely. Still another difficulty arises from the fact that the disease is transmitted indirectly much more frequently than directly, since children naturally remember with less distinctness the diseases of their collateral relations than those of their parents. Finally, it is not to be for- gotten that, as a rule, the pedigree of the disease is not identical with the pedigree of the family name, and that consequently the disease is more difficult to trace genea- logically than it would be if it were transmitted only agnatically, i. e., only through the male relatives bearing the family name. Experience shows, however, on the contrary (see further on), that the cognatic or maternal influence plays a far more important role than the agnatic in the propagation of bleeders; hence, we com- monly find that, in consequence of the marriage of the females into other agnatic circles, the group of individuals which forms the bleeder family, and which is com- posed for the most part cognatically, is distributed among several families bearing different names. Numerous instances of this kind are to be found in the literature 20 IMMERMANN.—HAEMOPHILIA. of hsemophilia (see Grandidier); still the number of these, as well as of reported hereditary cases in general, would undoubtedly have been much larger if family traditions were not so commonly monopolized by the agnatic family history to the almost total neglect of the cognatic record. 2. Sex. The predisposing influence of the sexual character should be mentioned immediately after the family hereditary disposition, not only because it ranks next in importance, but also because it is ordinarily connected with the latter m a manner that is extremely characteristic. In general, it may be said at the outset that fully developed haemophilia occurs with very much greater frequency in male than in female individuals. The evidence upon this point is overwhelming. The earliest cases, reported by Alsaharavi, A. Benedictus, Hoechstetter, and Banyer, were all male bleeders ; while in recent times, Otto, Hay, Nasse, Wachsmuth, and many other writers, have specially insisted upon this peculiarity of the disease, and their opinion is amply confirmed by the large mass of evidence now in existence. Thus, a compilation of all the reported cases of well-marked haemo- philia, in which the sex was noted, discloses the remarkable fact that the fully formed anomaly has been observed nearly thirteen times more frequently in male than in female individ- uals. Out of 650 of these cases there were only 48 females to 602 males—a proportion, therefore, of 1 to 12.6; or, expressed in percentages, 8 per cent, females to 92 per cent, males. In scarcely any other affection is the predisposing influence of sex so strikingly noticeable. This prevalence of haemophilia in the male sex is equally a characteristic of individual bleeder families. Thus, when several cases have occurred in a small circle of this kind, it is much more common for the sons alone to be affected, rather than the sons and daughters, or the daughters alone. When the disease appears in both sexes, moreover, the number of mule bleeders usually far exceeds that of the female bleeders ; and finally, the instances are much more numerous where all the sons without exception are bleeders than where the disease attacks all the children (both sons and daughters), or all the daughters alone. Such facts as these show clearly that the influence of sex in predisposing to the ETIOLOGY.—SEX. 21 anomaly in question is not merely a general law governing the gross statistics of the disease, but is likewise a radical differential principle, the operations of which are special in character, and discernible even in the smaller groups represented by the children of single families. The statistical material available for the study of these special operations of the law is naturally much smaller than that which we were able to use above for the general comparison, since most of the reports of bleeder families fail to give the number and sex of the children who are not bleeders. Still, taking the instances compiled by Grandidier in which these particulars are noted, and adding the instances recently recorded, we have a total of 76 bleeder families available for our purpose. In these families the comparative distribution of the disease between sons and daughters was as follows: Sons were affected in................................ 70 families. Daughters were affected in........................... 15 " In children of the same parents, therefore, the disease occurred 4.7 times more fre- quently in the sons than in the daughters. Sons alone affected in................................61 families. Sons and daughters both affected in.................. 9 " Daughters alone affected in........................... 6 " Consequently the sons alone were affected 6.8 times more frequently than the sons and daughters together, and 10.2 times more frequently than the daughters alone. Furthermore, the composition of the 76 families with respect to the sex of all the children (bleeders and non-bleeders) was as follows: Sons and daughters both............................. 60 families. Sons alone......................................... 13 " Daughters alone..................................... 3 " Now, we have seen above that out of these sixty families containing children of both sexes, there were only nine instances in which both sexes were affected; this leaves fifty-one instances in which the disease was confined to the sons, notwith- standing the coexistence of daughters. Consequently, in families containing children of both sexes the affection occurred 5.7 times more frequently in the sons alone than in the sons and daughters together. Again, with respect to the limita- tion of the disease to the daughters, we find that out of the six instances mentioned above, three occurred in families which contained no sons, leaving only three instances, therefore, in which daughters were exclusively affected, notwithstanding the coexistence of sons. It is clear, therefore, that when children of both sexes existed, the exclusive limitation of the disease to the sons occurred far more fre- quently than the exclusive limitation to the daughters, for the former occurrence 22 IMMERMANN. —HAEMOPHILIA. was noticed fifty-one times out of a possible sixty, and the latter only thrice—a relative proportion of seventeen to one. The prevalence of male bleeders among the children of the same parental pairs is shown also by the following table, giving the comparative numbers of male and female bleeders in the nine families in which the sons and daughters were both affected: Total number of male bleeders in these nine instances............ 40 female " " " " ............ 11 The total number of bleeder sons, therefore, in these circles of brothers and sisters was 3.6 times larger than that of the bleeder daughters. Furthermore, in the fifty-nine instances in which sons only were affected and the exact number of these bleeders was stated, we find: Total number of bleeder sons................................ 170 or nearly three bleeder sons to each marriage. On the other hand, in the six instances in which daughters only were affected, and the exact number of these bleeders was stated, we find : Total number of bleeder daughters............................. 9 an average of only 1.5 bleeder daughters to each marriage. It appears, consequently, that the average number of female bleeders, when the disease is limited to the daughters in families containing children of both sexes, is only half that of the male bleeders in the much more frequent (nearly ten times more frequent) opposite cases in which the sons only are affected. It wrould seem, therefore, that the influence of the female sexual character in preventing the occur- rence of fully developed haemophilia makes itself felt even when in a particular family circle a special tendency to the production of female bleeders can be recog- nized, since the tendency in most of these instances is restricted to much narrower limits than is the case with the male bleeders. Finally, the preponderance of male over female bleeders is also shown by the fact that the implication of all the sons in a given family is much more frequent than the implication of all the children (both sons and daughters), or of all the daughters alone. While the former event, according to reliable accounts, has happened twenty-seven times, the implication of all the children has occurred only three times, and that of all the daughters alone only four times. Three out of these last four families, it will be remembered, contained no sons, while of the twenty-seven families in which all the sons were bleeders, there were only eight in which no daughters existed. Now, although the foregoing details prove beyond the least question that the female sex is far less subject than the male to fully-developed haemophilia, it is still not to be overlooked, on the other hand, that the actual share of the female sex in the ETIOLOGY.—SEX. 23 entire number of cases, which probably belong to the pathologi- cal domain of haemophilia, is in all probability considerably larger than appears from the statistics already given, or than can possibly be shown statistically. For all the cases thus far con- sidered represent only the completely developed form of the disease, that is, only such varieties of hemorrhagic diathesis as are demonstrated to be genuine haemophilia by their congenital and habitual character. In addition to these, however, there is a large number of rudimentarily developed and anomalous cases, whose identity with haemophilia is far less clear, and whose comparative frequency therefore in the two sexes we have no means of determining with accuracy. Still, as Grandidier has pointed out, it is possible that such rudimentary cases, particu- larly those in which a certain degree of bleeder disposition is manifested only transitorily and at certain times (e. g., at the first appearance of the menses, in childbirth, etc.), are really more frequent in females than is commonly supposed, the true rela- tion of these attacks to haemophilia being overlooked in con- sequence of their trifling nature or brief duration. Of course, we are far from advocating the indiscriminate admission of every transitory hemorrhagic diathesis of this kind to the category of haemophilia ; on the contrary, the position assumed earlier in this article is ever to be kept in mind, viz., that the congenital and habitual character enters into the definition of the bleeder disease as an essential element, and that probably in all cases haemophilia is to be regarded as an affection which depends upon an original and permanent structural vice. Only those cases of transitory hemorrhagic diathesis, therefore, can be pro- perly admitted which are fairly entitled, notwithstanding their temporary clinical character, to be considered as merely the momentary expression (or, more correctly, "the outbreak") of a really permanent, though usually latent, morbid disposition. We are clearly warranted, however, in suspecting the existence of a congenital disposition to hemorrhages, and therefore haemo- philia, whenever the individual, male or female, who is momen- tarily the subject of a severe and almost uncontrollable hemor- rhage, without ever having suffered from decided haemophilia (habitual hemorrhagic diathesis), comes from a bleeder family, 24 IMMERMANN.—HAEMOPHILIA. perhaps has bleeder brothers and sisters or bleeder children; in short, therefore, whenever such a patient, notwithstanding his apparently perfect health in other respects, still stands under the ban of an hereditary tendency to attacks of danger- ous bleeding. These etiological considerations, as we have already inti- mated at the outset of the present chapter, certainly point to the desirability of enlarging our conception of haemophilia in some way so as to include at least all those imperfectly devel- oped cases of hemorrhagic diathesis which exist alongside of the complete forms of the disease in both sexes among the members of bleeder families, and manifest themselves at some time or other by actual clinical symptoms (hemorrhages). Still, any attempt to introduce these rudimentary cases into the statistical register of haemophilia would be thwarted, not only by the want of exact- ness in existing observations, but also more especially by the fact that these cases in their minor degrees of development, such as are seen with special frequency in females, are entirely indis- tinguishable from a condition of apparent good health, or, in other words, from a complete latency of the congenital bleeder disposition. So long, however, as we are unable to compute these rudimentary cases, an exact calculation of the comparative frequency of haemophilia in the two sexes is obviously out of the question, and would doubtless remain so even if we possessed— as we certainly do not—a record of all the fully developed forms of the disease. Still, there can be no reasonable doubt of the very marked preponderance of frequency of the disease in the male sex. The expressions used above—apparent good health, or, still better, complete latency of the bleeder disposition—warn em- ployed in contrast with the attribute of actual and perfect health, for the purpose of designating the bodily condition com- mon to all those members of bleeder families, who, without being themselves bleeders, are still able to transmit the anomaly hered- itarily to their own offspring. We have already seen that the propagation of haemophilia takes place in reality far more frequently by indirect than by direct transmission, that is, rather through the non-bleeder brothers and sisters than through the ETIOLOGY.—SEX. 25 bleeders themselves. Now, to abandon the law of continuity in these cases, and to suppose that the disease constantly passes over the intermediate members and renews itself de novo, is certainly contrary to our fundamental conceptions of natural processes. In fact, the undiminished severity with which the disease reappears in the children of these individuals, compels us to infer that the soundness of the latter is not actual, but only "apparent," and that they are really subjects of a latent bleeder diathesis. It is clear, however, that if we are to take into con- sideration the nature, and not merely the external manifesta- tions of the anomaly, we shall strictly be compelled to include in the category of haemophilia also all those completely latent cases in which individuals who have never themselves bled in a morbid manner continue to give birth to one child after another bearing the unmistakable impress of the disease. Regarded in this light, the relative shares taken by the two sexes in the affec- tion appears widety different from those shown by statistics which deal solely with the external phenomena of haemophilia, and the highly interesting fact is disclosed that the female sex is in reality to be regarded as the more intensely affected, because it possesses in a far higher degree than the male, not merely the opportunity, but also especially the capacity for transmitting the disease by inheritance to its own offspring. For, in by far the majority of instances where haemophilia is transmitted to one or more children, and where consequently a multiplication of individual cases of the disease takes place, this result is brought about, not through a male (bleeder or non-bleeder) member of a bleeder family, but directly through a female member. That this peculiarity, moreover, is by no means wholly dependent upon the excessive premature mortality of the (mostly bleeder) male members of these families, but is rather directly connected with a more active transmitting power on the part of the female members, is apparent from the following important and interesting facts (Grandidier): 1. Males in bleeder families, who are themselves bleeders, do not, as a rule, beget bleeder children by women who belong to non-bleeder families ; in fact, the children in this case are usu- ally healthy and non-bleeders. On the other hand, the children 26 IMMERMANN. —HAEMOPHILIA. of women who are themselves bleeders are quite uniformly sub- jects of haemophilia. 2. Males in bleeder families, tolio are not bleeders^ almost never beget bleeder children by women from other families. On the other hand, among the children of women who belong to bleeder families, without being themselves bleeders, there are almost always some who suffer from pronounced haemophilia (see above). It is clear, therefore, that in the transmission of haemophilia the maternal influence is far more important than the paternal, for while the female members of these families appear to be capa- ble of propagating the disease, whether they are bleeders or not, the males rarely manifest this capacity except when they are themselves bleeders, and even then the chances of transmission are much less than in the case of a latent disposition on the mother's side. Since now, as we have already remarked, the females are rarely fully developed bleeders, and the male bleeders either die prematurely, or, as a rule, fail to reproduce the disease in their children, it follows that the non-bleeder women in bleeder fami- lies are in fact the most frequent and most efficient" conductors" (Vieli, Grandidier) of haemophilia, and that to them the hitherto constantly increasing spread of the affection is mainly due. In the two large bleeder families at Tenna, in Graubiinden, Vieli found that the males had never transmitted the disease, although they had all been bleeders with but a single (!) exception, their children by intermarriage with other families having been invariably sound and free from haemophilia. On the other hand, during the entire period of the existence of the disease in these families—nearly a century— none of the women, so far as could be discovered, had ever clearly manifested the bleeder diathesis; and yet, with the single exception referred to, the sons of these non-bleeder women had all been bleeders. In other families, however, an agnatic transmission of the disease, that is, from father to son, has been observed in several instances (Schuenemann, Reinert [11. cc], etc.); still, such an occurrence is compara- tively rare, while the appearance of haemophilia in the children of non-bleeder males in haemophilist families is so very exceptional that Grandidier expressly mentions' his inability to find a single example among the numerous cases of haemophilia reported in Germany and Switzerland. Isolated instances of the kind have, how- ever, been observed by English writers, particularly Legg.2 There seems to be no reasonable doubt, therefore, that the most frequent mode of propagation of hosmophi- 1 Schmidt's Jahrbiicher. CLIV. S. 96. s 1. c. p. 127. ETIOLOGY.—AGE. 27 lia is by means of indirect transmission in a cognatic direction ; hence the appropri- ateness of the term " conductors," which was first employed by the inhabitants of Tenna, and afterwards became generally adopted as a designation for the non- bleeder women of haemophilist families through whom the disease is transmitted. 3. Age.—Inasmuch as haemophilia is probably always of con- genital origin, we can properly speak of a predisposing influence of age only in so far as the first outbreak of the affection tends to occur at particular epochs in the physiological course of the vital processes more frequently than at others. Now, all observa- tions go to show, as we have already intimated (see Definition of the Disease), that the first bleedings of haemophilia, in by far the majority of instances, take place in very early childhood, and are decidedly rarely postponed to a later period. Still, except from traumatic causes, marked hemorrhages of this character do not often make their appearance so early as immediately during birth, or during the first few days or weeks of life, while the occurrence of the so-called spontaneous bleedings at these times is quite exceptional. At all events, as Grandidier particularly insists, the great majority of the so-called spontaneous umbilical hemorrhages of new-born children are not to be considered, notwithstanding their apparently congenital character, as the manifestation of an actual bleeder diathesis, since they are not specially frequent, but rather rare in bleeder families, and are, moreover, not apt to be followed in after-life by an habitual dis- position to hemorrhages. On the other hand, as was indirectly intimated above, traumatic hemorrhages of an obstinate and even fatal character have been repeatedly observed in the children of bleeder families after the most trifling wounds. Thus, quite a number of deaths have been reported in Jewish families from the rite of circumcision on the eighth day, as well as similar results in other families from cutting the frenum linguae soon after birth, or from accidental wounds (see the fuller consideration of this point under the Terminations of the Disease). While it is evident, therefore, that the congenital bleeder diathesis may manifest itself under favoring circumstances very prematurely, the most com- mon time for the full outbreak of the disease is at the end of the nursing period, or at the beginning of the first dentition, not only because the traumatic bleedings now become more frequent in 28 IMMERMANN.—HAEMOPHILIA. consequence of slight contusions, excoriations, etc., but especially also because about this time the apparently spontaneous bleed- ings begin to make their appearance. Occasionally these latter hemorrhages do not occur until the second year or even later, while in its subsequent course the disease, notwithstanding its essentially stationary character, frequently presents fluctuations, with periods of aggravation, during which the bleedings are more frequent and more readily produced, present a more obstinate character, and are specially dangerous to life. Accordingly we find that there are certain ages, viz., those with which these periods of aggravation usually coincide, when the disposition to bleedings is particularly marked. Thus, Grandidier calls atten- tion to the fact that the second dentition, puberty, and in females the first appearance and the cessation of the menses, are specially critical periods for these patients ; and although this rule is not without occasional exceptions, its general correctness is proved by the experience of most of the reported cases. Finally, it is also to be noted that with the advance of age there is very gener- ally a gradual decline in the average intensity of the affection, and that accordingly the manifestations of the congenital anom- aly are commonly found to be most marked in youth, and to become much feebler as the individual approaches middle life. In exceptional instances, however, the symptoms of haemophilia recur again and again with undiminished intensity up to old age, and even at this period death may result directly from one of the hemorrhages. As regards the relation which the spontaneous umbilical hemorrhages of new-born children bear to haemophilia, it appears from the investigations of Grandidier' in 228 cases of hemorrhagia umbilicalis neonatorum, that out of this number only 14 occurred in bleeders belonging to eleven different bleeder families, and that nearly 94 per cent., therefore, of these hemorrhages were due not to haemophilia, but to other causes. Moreover, on comparing this statistical result (14 cases of umbilical hemorrhage in eleven bleeder families) with the large number of cases of haemophilia thus far carefully reported (650 cases in 219 families), it is evident that this form of hemorrhage is far from common in bleeder circles, and is very much loss frequent than the traumatic and spontaneous hemorrhages. 1 Die freiwilligen Nachblutungen der Neugeborenen. Cassel, 1871; also Schmidt's Jahrbucher. Bd. CLIV. p. 95. ETIOLOGY.—CONSTITUTION, TEMPERAMENT. 29 With respect to the time of the first outbreak of the affection, exact data are wanting in a large proportion of the reported cases. Still, in most of the accounts it is stated that the individuals affected had been subject to dangerous hemor- rhages " from early childhood." In 95 cases, however, Grandidier succeeded in ascer- taining the time when the first hemorrhage occurred, as shown in the following table: In the 1st year of life.... n 2d (( .... 8 " (i 3d (c ....3 " (i 4th u 2 " k 5 th (« ....5 " a 6th (< .... 5 " it 7th u tH K 8th u tH In the 9th year of life........ 1 time. 10th 11th 12th 14th 15th 17th 22d 4 times. 1 time. 1 " 1 " 1 " 1 " 2 times. According to this table 69.5 per cent, of the first outbreaks occurred in the first two years of life, and 61 per cent, in the first year alone. In all probability, how- ever, the share of the first year would be much larger if the statistical material were sufficiently extensive to give the true percentages. Furthermore, it is to be parti- cularly noted that the twenty-second year appears to be the very latest limit up to which the congenital and hereditary disposition to haemophilia can remain latent, and thereafter develop into the pronounced and habitual disease. For, even in the cases in which the date of the onset of the affection has not been recorded, it is reasonably certain from statements in the reports that the anomaly had already manifested itself in childhood and youth, and, therefore, previous to the twentieth year. Whether, however, the same rule holds good also for those rudimentary forms of the disease whose manifestations are often of only a transitory nature, and whose only claim to be regarded as haemophilia rests upon the fact that the affected individuals belong to bleeder families, must for the present remain undetermined. 4. Constitution, Habitus, Temperament.—There appears to be no one definite form of physiological constitution which exhi- bits a specially marked predisposition to haemophilia; on the contrary, the varying accounts given by writers of the condition of the bodily functions in bleeders and bleeder families render it probable that, apart from the tendency to dangerous hemorrhages which characterizes the pronounced form of haemophilia, and the capacity for transmitting the anomaly inhering even in individu- als with the latent disposition, the constitution of bleeders may differ widely in individual cases. Some authors, it is true, have 30 IMMERMANN.—HAEMOPHILIA. distinguished, according to the nature of the constitution, two distinct forms of haemophilia, viz., an erethistic and a torpid variety, and have maintained the greater frequency of the latter, that is, the more frequent coincidence of haemophilia with torpor of the vital processes. We fail, however, to find any warrant for such a distinction ; indeed, the very fact that the affection occurs as well in connection with a more active flow of the vital processes—the so-called erethismus of the constitution—shows conclusively that no essential etiological relation exists between haemophilia and either of these constitutional states; not to mention that the terms themselves, " erethismus " and " torpor," have been and still are frequently used without any clear con- ception of their meaning. Just as it is highly probable, therefore, that there is no spe- cial form of constitution l by which bleeders are characterized, so these individuals possess no distinguishing habitus. The muscular and osseous systems may be strongly or imperfectly developed, and while a tendency to obesity is noticeable in many cases, in others it is wanting. Some writers have attached importance to the color of the hair, skin, and iris, and assert that blond or reddish hair, a pale and but slightly pigmented skin, and blue eyes, are particularly frequent in bleeder-fami- lies ; still the disease is by no means uncommon in dark-haired, brunette individuals with brown or black eyes. One peculiar- ity, however, viz., a certain delicacy and transparency of the general integuments, together with a superficial position and marked fulness of the subcutaneous vessels, particularly the veins, is mentioned by trustworthy observers (Otto, Nasse, Wachsmuth, Schonlein, Virchow, Grandidier, Vieli) as so com- monly noticeable in bleeders, that we can scarcely deny it a cer- tain causal relation to the bleedings of haemophilia, especially since these peculiarities in the position and fulness of the super- ficial vessels are accompanied also by certain anomalies in the structure of the coats of the vessels (see Anatomical Changes), which may likewise be urged with some force in favor of a vas- 1 The word constitution is used here as in Vol. XVI. (p. 252), to express the sum- total of the vital processes in relation to the mass of matter set in motion, and the velocity and direction of its movement. ETIOLOGY.—RACE AND NATIONALITY. 31 cular theory of haemophilia, and at all events deserve full con- sideration. Finally, as regards the temperament and mental endowments of bleeders, no universal or even general rule can be deduced. Whether, as asserted by some writers, a phlegmatic tempera- ment is really "somewhat" more common in these patients than the choleric and sanguine, must for the present remain doubt- ful ; certain it is, however, that in several instances the individ- uals are described as very vivacious, and possessing an ardent, even passionate disposition (Wachsmuth). Inasmuch, therefore, as the most diverse forms of temperament are compatible with the bleeder disposition, it is hardly likely that we shall discover any important predisposing factor in this direction. Nor is the inquiry more promising when we come to the mental endow- ments, for although some bleeders are described as deficient in intelligence, others are highly spoken of for their clear-headed- ness, quick perception, artistic talents (music, painting, "ver- sification"), etc. ; indeed, it must be evident from the contrariety of these descriptions, interesting as such hors-d'aeuvres undoubt- edly are in the histories of patients, that little or nothing is added by them to our knowledge of the etiology of haemo- philia. 5. Race and Nationality.—The scantiness of accurate reports as to the occurrence and frequency of haemophilia in numerous non-European countries—as was noticed in our introductory sketch of the geographic distribution of the disease—makes it impossible to decide whether race really exerts a predisposing influence or not. Still our sketch, it will be remembered, revealed at least one interesting fact, viz., that in those portions of the Old and New World which are inhabited by Europeans or persons of European descent, the frequency of the disease appears to be largely influenced by the nationality of the popu- lation, the Anglo-Germanic race exhibiting a special disposition to the affection. A similar predisposition, it may be added, seems to exist also in the widespread Jewish race, since as we have already seen, the disease has been repeatedly noticed among this people in connection with the rite of circumcision, while of the total number of bleeder families thus far reported a consider- 32 IMMERMANN.—HAEMOPHILIA. able proportion have been Israelites (Grandidier). With these remarks we must dismiss the subject of predisposing influences, and pass now to a brief consideration of the determining causes of haemophilia. B. Determining Causes. Under this head are to be included all influences which appear either to develop hamophilia de novo, i. e., to induce its first appearance in a family circle, or to awaken the latent dis- position to an actual outbreak. With respect to the primordial causes of haemophilia, we are still in complete ignorance ; nor does the origin of the disease in any considerable number of families appear to have been due to their common exposure to influences of a similar character. It is clear that in an affection which, like haemophilia, apparently always depends upon a congenital morbid idiosyncrasy, the physical peculiarities of the parents (in cases where the disease occurs to all appearance spontaneously in the children without evident hereditary transmission) certainly deserve special at- tention. Investigation upon this point has, however, failed to give any uniform result, the parents and ancestors in some of these cases having according to all accounts enjoyed perfect health, while in others various family diseases are mentioned, as gout, scrofula, and affections of the heart and lungs (Grandidier). Furthermore, the opinion entertained by some writers (Har- ris) l that consanguineous marriages, to which so many other disastrous results are ascribed, induce also haemophilia in the offspring, has by no means been proved, although coincidences of this kind may be occasionally noticed; nor is there anything in the records of individual cases, or of series of cases, to show that any other fact whatever, external or internal, con- cerned in procreation and conception, could have played a definite role in the etiology of the disease. Finally, influences upon the mind of the mother during pregnancy, especially such 1 Philadelphia Medical Times. Vol. II. p. 38. DETERMINING CAUSES. 33 as excite violent emotions (terror, anger), have also been regarded as determining causes of haemophilia by many writers (Miitzen- becher,1 Andre2); still, the facts in such cases are so apt to be distorted by the influence of preconceived opinions that it is easy to imagine a genetic relation where there is really nothing but the operation of mere chance.3 It must probably be admitted, therefore, that the entire ques- tion as to the nature of the influences which operate originally in the genesis of haemophilia still remains to be settled, and that the pathology of the disease, so far as regards this vital point in the etiology, is still wrapt in complete obscurity. On the other hand, the determining causes of the bleedings, that is to say, the influences which are able to excite an outbreak, when the disposition, however acquired, already exists, are much better understood, and are briefly as follows : The characteristic hemorrhages of haemophilia are most gener- ally induced by injuries which sometimes produce an actual solution of continuity with escape of blood upon the surface, at other times merely an interstitial extravasation without any true wound (solution of continuity). Cuts, punctures, incised or lacerated wounds, contusion and wrenching of the external soft parts by pressure, blow, or more forcible lateral displacement, may all act as exciting causes ; while as regards the mode in which these causes operate in bleeders it is especially character- istic that extremely obstinate and copious external hemorrhage, as well as a very extensive interstitial hemorrhage, occurs in these individuals not only after severe wounds and injuries, but quite commonly also even after the most insignificant traumatic acci- dents. Indeed, it seems as if it were just these very trifling 1 Dissertatio de Hasmorrhagicis. Heidelberg, 1841. 2 Schmidt's Jahrbiicher. Bd. LXXII. S. 192. 3 J. Wickham Legg, in his admirable Treatise on Haemophilia, London, 1872, p. 35, after taking essentially the same ground as the above, adds: ;' It is well, never- theless, not to lose sight altogether of the influence of the emotions, especially of the depressing emotions, in the production of hemorrhage. A sudden great fear is not uncommonly the starting-point of a hemorrhagic disposition in women; and the emo- tions of grief and anger may be followed by hemorrhages. I believe that the emotions have a far greater influence upon the tissues than is generally thought."—Tkans- lator's Note. VOL. XVII.—3 34 IMMERMANN.—HAEMOPHILIA. injuries, so harmless in healthy persons as to scarcely attract attention, that are specially dangerous in bleeders; in fact, the mortality statistics of haemophilia show that fatal hemorrhage results far more commonly from very slight than from severe wounds. Still we are not to conclude that the latter are unat- tended by danger to bleeders ; on the contrary, such wounds have been found to result fatally more frequently in them than in other persons (Grandidier), although the difference between bleeders and non-bleeders in respect to the clinical course of these more serious wounds and injuries naturally attracts less notice, for the reason that the latter are also dangerous even for non-bleeders. Add to this the further fact that with prudence on the part of the patient important lesions are far less likely to be met with than those of a very trifling character, and we have some explanation why it is that certain writers (Fordyce, Coates, Allan, Wachsmuth) have laid so much stress on the danger of insignificant, and so little upon that of serious injuries. There is certainly no doubt, however, that the most trifling lesions in bleeders may be followed by extremely alarming results, and in this respect the descriptions which these writers have given are by no means exaggerated. Thus, simple punc- tures, the opening of small superficial abscesses, the application of leeches and cups, the extraction of teeth, the cutting of the frenum linguae in young children, the ritual operation of cir- cumcision in Jewish bleeder children, as well as numerous other very trifling operative procedures, have been followed by uncon- trollable and ultimately fatal hemorrhages in so large a number of cases, that any operation upon these patients, however slight, attended by bleeding, must be regarded as dangerous. The same is true also in regard to slight accidental wounds of all kinds (pin-pricks, superficial abrasions of the skin, trifling contusions, etc.) ; these are likewise very apt to be followed by most obsti- nate and alarming external hemorrhages, or by very diffuse ecchy- moses of the soft parts; in fact, the much greater difficulty or even impossibility of avoiding such accidents makes them a specially frequent source of danger. Certain of these minor wounds (both the operative and the accidental) seem to be attended, as a rule, by much less risk than others. For example, DETERMINING CAUSES. 35 circumcision, the extraction of teeth, and accidental wounds of the head and face are spoken of as exceptionally dangerous in bleeders, while venesection and vaccination are regarded as less hazardous. Still, there are distinctions based entirely upon the hitherto observed rates of mortality, and consequently upon the prognostic differences which naturally exist between the indivi- dual forms of hemorrhages according to their nature and loca- tion, and do not materially alter the fact that even the forms which are alleged to be harmless, e. g., those following vaccina- tion, may at times be characterized by unusual abundance and obstinacy (Dequevauviller, Tardieu, Thai, Vieli), and, like the others, may even run a fatal course (Alsaharavi, Otto, Hughes, Miling, Rieken). Indeed, all clinical observation shows that any traumatic lesion in a bleeder, whatever its cause or situation, may excite a characteristic hemorrhage (external or interstitial), and may, therefore, be regarded as a possible cause of a haemo- philia bleeding. A remarkable exception to the general behavior of traumatic hemorrhages in bleeders seems to be presented, to a certain degree, by that attending the operation of vaccination. At least the reported cases of profuse bleeding after this operation have been exceedingly rare, two only having been recorded in the entire literature of haemophilia (Heyfelder,1 Stromeyer2). It is a curious fact in this connection that Rieken was so well satisfied of the innocuousness of vaccination in bleeders that he even recommended the operation as a prophylactic against further hemor- rhages.3 1 Med. Vereinszeitung. 1833. No. 48. 2 Die chirurgischen Krankheiten des Kopfes. 1864. S. 120. 3 Another instance of the danger occasionally attending vaccination in bleeders deserves to be mentioned here. In a case of marked haemophilia attended by Dr. W. G. Wylie, and seen also by Drs. Van Buren, Keyes, and myself (all of New York), it was ascertained tbat the patient, a young lady, had nearly bled to death from vaccination when six weeks old, and that several subsequent attempts at vaccination had all been attended by alarming hemorrhages; none of the attempts were successful. In later life repeated and profuse hemorrhages had occurred from the nose, gums (after extraction of a tooth), and bowels. During the summer of 1877 the patient died from peritonitis, suspected to have been excited by hemorrhage into the peritoneal cavity(?). This case, which Dr. Wylie informs me he intends to report in full, is unusually interesting, not only from the sex of the patient, and from the fact that the mother was also a marked bleeder, but also because this instance of the disease breaks the long silence of Ameri- can reports of hasmophrlia.—Translator's Note. 36 IMMERMANN.—HAEMOPHILIA. As regards the modus operandi of traumatic influences, it is noticeable also, according to trustworthy observers (AVachsmuth, Martin, Grandidier), that the danger from the same kind of wound, as a leech-bite or the prick of a pin, is not equally great at all times, and that the disposition to bleeder hemorrhages after wounds seems to vary considerably at different times. In our consideration of the predisposing causes particular attention was called to the existence of certain periods of life (p. 25) which are excessively dangerous and critical for bleeders, because traumatic hemorrhages occurring at these times present a spe- cially marked bleeder character; it may be added here that variations in the individual disposition to serious hemorrhages after wounds are likewise occasioned by other causes, the nature of which we are still unable to determine with certainty. Krimer's conjecture that the change of the moon exerts an influence upon the intensity of the hemorrhagic disposition seems to us scarcely compatible with present scientific conceptions. More credible, perhaps, are the statements of other writers, that traumatic hemorrhages in bleeders are more severe during changes of the seasons, in spring and autumn (Consbruch, Rieken, Wachsmuth, Grandidier, Martin), or during the sultriness of air preceding a thunderstorm (Martin); still, the evidence of a determining influence on the part of these atmospheric conditions is too im- perfect to warrant us in accepting it as conclusive. There remains to be considered another point of importance in this connection, viz., the influence of traumatic hemorrhages in modifying the future character of the disease. Almost all writers testify that the occurrence of a traumatic hemorrhage not only at times awakens a hitherto latent haemophilia, but also materially aggravates, at least for the time being, the manifes- tations of an already developed hemorrhagic diathesis. Thus, it has been noticed by Virchow, Grandidier, and others, that after the occurrence of a traumatic hemorrhage the patient is specially subject to the so-called spontaneous hemorrhages, both those in which the blood escapes externally and those of an interstitial character. Still the precedent occurrence of a trau- matic hemorrhage is not essential to the development of these spontaneous bleedings; they may occur independently of such DETERMINING CAUSES. 37 a connection, and may even constitute the initial manifestation of the disease. While, therefore, for many of these spontaneous hemorrhages we are able to find a determining cause in the previous occur- rence of a traumatic bleeding, in other instances unpreceded by an event of this kind, we are naturally compelled to search for other explanations. In these cases it is to be noted particularly that sometimes the hemorrhage occurs without any demonstrable exciting cause, and especially without prodromata, suddenly, as it were of its own accord; at other times, and in fact more fre- quently, the patient complains, before the hemorrhage, of flush- ings, a sensation of heat, and more forcible pulsations of the heart and arteries ; the face, especially the cheeks and the lobes of the ears, is markedly reddened and feels hot; there is also headache, together with sensitiveness of sight and hearing and mental excitement—symptoms, however, which usually all grad- ually decline and entirely disappear when the bleeding is once established (Buel, Elsasser, Rieken, Davis, Wachsmuth, Uhde, Virchow, Grandidier, and others). Now these molimina, which evidently stand in an indirect causal relation to the ensuing hemorrhage, are obviously to be interpreted as the expression of an increased arterial tension, perhaps also of an abnormal fulness of the entire vascular system; hence the spontaneous hemor- rhages which are thus characterized may properly be distin- guished as fluxionary (Virchow) or possibly even as plethoric hemorrhages. The pertinency of these designations is shown, moreover, by the fact observed by Grandidier that many of these hemorrhages are very clearly induced by influences which excite a more forcible action of the heart (the use of alcoholic stimu- lants, mental emotion, physical exercise), or which suddenly increase the mass of the blood (copious drinking). It is notice- able, on the other hand, that these prodromata—the molimina above described—are rarely observed when the spontaneous hemorrhages have been preceded by a trauma, for the reason that, under these circumstances, the anaemic condition of the patient naturally precludes any considerable congestion, parti- cularly any plethora. To summarize, finally, our present knowledge of the exciting 38 IMMERMANN.—HAEMOPHILIA. causes of the hemorrhages of bleeders, the result is briefly as follows: In bleeders the hemorrhages are most frequently of a directly traumatic origin, but they may also occur without the reception of any wound or mechanical in- jury (spontaneous hemorrhages). Still, many of even the latter hemorrhages are indirectly traceable to the influence of a recent wound, since it is found that after such an event the tendency to spontaneous hemorrhages is considerably increased, or, it may be, is for the first time awakened. When, on the other hand, there has been no antecedent traumatic hemorrhage, the spontane- ous bleedings generally manifest a distinctly fluxionary character, and are preceded by various symptoms of congestion and plethora. Finally, in rare instances the spontaneous hemorrhages seem to occur independently of any manifest external or internal cause, with every appearance therefore of actual spontaneity, and must accordingly be regarded, until the subject is better understood, as the result of unknown influences. Pathology. Description of the Disease and Symptoms. Since haemophilia, as was insisted upon at the very outset ol our subject, is not, properly speaking, a morbid process in the ordinary sense, i. e., a constantly changing pathological event with a typical course, but rather an abnormal state of the cor- poreal organization or a morbid disposition, it is evident that the manifestations of this somatic vice may be modified in an unusu- ally varied manner, according to the other external and vital conditions of the individuals affected. A complete picture of the disease is therefore out of the question, and we shall accord- ingly confine ourselves, first, to a statement of the nature and general type of the pathological symptoms by which the anomaly usually manifests itself, with a somewhat full description of DESCRIPTION OF THE DISEASE. 39 their most important characteristics ; and secondly, but with less detail, we shall consider the special modifications which the typical manifestations of the anomaly are found to undergo according to the time of their occurrence, their determining causes, their particular localizations, etc.—in brief, therefore, according to their accidental relations. The symptoms of haemophilia, as the usual name of the affec- tion denotes, and as we have repeatedly had occasion to men- tion, are essentially of a hemorrhagic character, so that the following sketch of the symptomatology will consist in the main of a more complete description of the haemophilia bleedings, which, according to their anatomico-clinical aspects, may be di- vided into two leading varieties : first, the external hemorrhages, in which there is an extravasation of blood upon the free surface of the bleeding part; and secondly, the interstitial hemorrhages, in which the blood penetrates into the interstices of the bleeding tissue. While this generally adopted distinction will be ob- served in the following remarks, it should be borne in mind at the same time that the same bleeding-point not infrequently gives rise to both varieties of hemorrhage; for example, an external bleeding may be followed by a hemorrhagic infiltra- tion of the bleeding tissue, and, on the other hand, after an inter- stitial hemorrhage the blood may ultimately force its way to, and stream from, the bleeding surface. Most of the hemorrhages can, however, be referred without much difficulty to one or the other of these categories, or at least belong in their main features to one rather than to the other, so that we are on the whole practically justified in considering the two forms separately. A still more urgent reason for this course is the difficulty of adequately describing, by any other method, the important clinical differences which the two forms of hemorrhage present, not only with respect to their usual situa- tion, but also in their entire mode of progress and their concomi- tant symptoms. 1. External hemorrhages.—These maybe subdivided, accord- ing to their genesis, into the traumatic and the so-called spon- tetneous hemorrhages (see Etiolog}*). In the first variety, the location of the hemorrhage depends upon the site of the lesion, 40 IMMERMANN.—HAEMOPHILIA. and is therefore unrestricted, since wounds may naturally occur in any part of the body. It is obvious, however, that traumatic external hemorrhages must take place most frequently from the skin and superficial parts, because these by their very position are most exposed to injuries likely to excite hemorrhage. Finally, in this form of hemorrhage, the bleedings are much more frequently single than multiple, as might naturally be expected from the fact that they are usually due to very trifling accidents, and are confined to the immediate site of the lesion ; so that we never meet with several bleedings of this kind occurring at the same time, except in those rare in- stances in which wounds have been inflicted simultaneously on different parts of the body. The behavior of the spontaneous superficial hemorrhages, on the other hand, is somewhat different in these respects. Thus, there is not only a more definite and more pronounced predilection for certain parts of the body and for certain tissues, but also a more frequent tendency to the occurrence of simultaneous hemorrhages from different localities. The favorite situation of these hemorrhages is the mucous mem- branes, particularly those of the nasal and oral cavities (the gums) ; next in frequency, those of the genito-urinary appara- tus, bronchi, stomach, and intestines; more rarely the conjunc- tivae and the skin of the external auditory passage, and still more rarely the external skin, provided its normal histological structure and its natural resistance and vascularization have been preserved. On the other hand, these hemorrhages are compara- tively frequent wherever the skin has been inflamed, ulcerated, or filled with blood from an interstitial hemorrhage, or where there are recent, still highly vascular cicatrices resulting from pre- vious wounds. In certain bleeders, however, bleedings which are independent of any wound, and which may therefore be regarded as spontaneous, take place from the intact skin of the tips of the fingers, the toes, lobes of the ears, nose, and back of the head (Coxe, Merkel, Adelmann). Rarest of all appear to be the ex- travasations of blood into the internal cavities ; at least only a few cases of this kind have been described in the entire literature of haemophilia. The comparative infrequency of these hemor- rhages is naturally to be explained by the more protected posi- DESCRIPTION OF THE DISEASE. 41 tion of the cavities concerned; still, the very fact that hemor- rhages do occur also in these more deeply-seated localities, shows that the bleeder diathesis is not confined to the superficial parts, but is quite general, and extends to all regions of the body. Of hemorrhage into the abdominal cavity two cases have thus far been directly observed (Grandidier, Lemp, 11. cc), in one of which blood was extravasated at the same time into the tunica vaginalis testis. A third instance of peritoneal hemorrhage was not directly observed by the writer who reported it (Brigstock, 1. e.), but its occurrence was inferred from the history of the case.—Of intermenin- geal apoplexies in bleeders only four cases are recorded (Wilson (2), Cousins (1), Tranfius (1) ;' while of hemorrhages into the pleural and pericardial cavities not a single one is reported. On the other hand, judging by the clinical symptoms in the large number of cases in which bleeders have suffered from inflammatory arthritic affections (see Complications and Sequela;), it is highly probable that san- guinolent effusions into the various synovial sacs have been of frequent occurrence (Dubois,2 Ainmann,3 Assmann4), although as yet this point has not been demon- strated autopsically. From the two statistical compilations made by Grandidier some time since, we have drawn up the following table, showing the comparative frequency of spon- taneous bleedings in different parts of the body in 308 carefully described cases. Hemorrhage from the nose............................ 152 times. " " gums........................... 38 " " " intestines........................ 35 " Haemoptysis.......................................... 17 Hematuria.......................................... 16 " Haematemesis........................................ 14 " Hemorrhage from the female genitalia................. 10 " " tongue.......................... 6 " " external auditory passage.......... 5 " " tips of the fingers................. 4 scalp............................ 4 " " caruncula lacrymalis.............. 3 " " ulcers of the skin................ 2 " " the upper eyelids................. 1 " umbilicus long after healing....... 1 " The above table, which of course comprises only a small fraction of the spon- taneous hemorrhages that have actually occurred in bleeders, shows at least that epistaxis is by far the most frequent form. 1 St. Louis Med. and Surg. Journal. N. S. VII. p. 535. 1870. 2 Gazette Medicale de Paris. 1838. p. 43. 3 Schmidt's Jahrbucher. CLIV. S. 91. 4 Die Haemophilie. Dissert. Berl. 1869. 42 IMMERMANN.—HAEMOPHILIA As regards the mode of escape of the blood in the external hemorrhages of haemophilia (both the traumatic and the non- traumatic), all the descriptions of writers agree that the bleeding takes place, as a rule, not from large vessels, but from numerous vessels of the smallest size (capillaries). On inspection, therefore, of the bleeding part, it has only rarely been possible to distin- guish any particular vessels from which the blood was escaping in a jet or stream ; on the contrary, the extravasation has almost always been found to take place, after the manner of the so- called parenchymatous bleedings, from a great number of minute openings, as if from the pores of a compact sponge saturated with fluid (Wachsmuth, Grandidier, Vieli, Virchow, and others). Notwithstanding, however, the usually capillary character of these hemorrhages, the blood is poured out under a compara- tively very strong pressure, as is shown not only by the rapidity with which a large quantity of blood is lost from even a small surface, but also by the great difficulty of checking the bleeding by means of external compression. For, usually, on every attempt to control the bleeding by pressure with the finger or a compress, the blood very soon wells up at the side, while at the same time, or generally even before this result is noticed, an extensive ecchymosis (interstitial bleeding) takes place in the surrounding parts (Buel). The danger, however, lies not so much in the force of the hemorrhage, that is, in the rapidity or momentary pro- fuseness of the loss of blood, as in its extensive duration; in fact, it is this obstinate persistence of every hemorrhage, what- ever its origin, which is the most importojit and at the same time the pathognomonic peculiarity of the bleeder diathesis. Thus, it is by no means an uncommon experience in these cases to find that an originally trifling hemorrhage, which there was every reason to expect would soon cease spontaneously or yield to treatment, still persists, in spite of all efforts to check it, not only for hours, but even for days and weeks together, and finally reduces the unfortunate patient to a state of extreme anaemia, or even destroys life (see Terminations). The symptoms which arise during the course of such protracted hemorrhages, and, it may be, usher in a fatal result, are naturally the same as are ordinarily met with in extreme anaemia, viz., marked decoloration of the skin DESCRIPTION OF THE DISEASE. 43 and visible parts, the facies Hippocratica, a small, soft, and finally scarcely perceptible pulse and heart-beat, a blowing systolic mur- mur over the heart, and usually, so long as the circulation retains a certain degree of force, a loud venous hum in the cervical veins; finally, extreme exhaustion, hallucinations, delirium, turns of faintness, and even actual syncope, in which the patient lies for some time in a condition simulating, and often terminating in death. The fatal result in these conditions of extreme prostra- tion usually takes place with complete loss of consciousness, or with convulsions, such as occur in the anaemia produced by loss of blood under other circumstances, or else, with the symptoms of simple syncope (paralysis of the heart). On the other hand, the occurrence of syncope appears by no means infrequently to be the means of saving the life of the patient; for, after all efforts to check the hemorrhage have failed, the bleeding sometimes at last ceases of its own accord during a death-like swoon, and life is gradually restored after the patient has lain for hours or days in a sort of vita minima, waxy pale and unconscious. Indeed, even more remarkable than the severity of the hemorrhages are the marked tolerance with which bleeders bear great losses of blood,, and especially the rapidity with which restitution of the blood-mass is usually effected even after enormous extravasa- tions. When we consider that these losses of blood often amount to several pounds, and not infrequently recur several times at comparatively short intervals, it must certainly be a matter of surprise that a fair degree of health is in general so long preserved, or so speedily regained when temporarily lost; that in fact so many of these individuals even present a fresh, well-nourished aspect, frequently complain of flushings (see Eti- ology), and are at the farthest possible remove from any appear^ ance of anaemia. We give here a few instances in which the quantity of blood lost has been par- ticularly noted. Thus, Coates's patient is stated to have bled three gallons (24 pounds) in eleven days, Hay's patient two quarts for several days in succession, and Smithharst's patient three pints. In Krimer's case four pounds and a half of blood were lost within twenty-four hours after the extraction of a tooth, and in Schaefer's case from three to four pounds daily for several days after the same operation. In a new-born infant, belonging to a Jewish bleeder family, Thai found 44 IMMERMANN.—HAEMOPHILIA. after the circumcision a quart of coagulated blood covering the parts adjacent to the wound. Uhde was informed by a patient, a man forty-four years of age, that his periodically recurring spontaneous bleedings from the nose, gums, etc., lasted, as a rule, for more than a week and until he became completely unconscious; for several days afterwards he lay in a death-like stupor, then gradually returned to life and consciousness, and convalesced, at first slowly, but afterwards, with the return of appetite, so rapidly that within a few days he again " bloomed like a rose." With respect to the composition of the effused blood, numerous reports are to be found in both the earlier and more recent litera- ture of haemophilia, but only very few careful microscopico- chemical examinations. The pale color and watery consistence of the effused blood, mentioned by almost all writers as notice- able during the later stages of the hemorrhage, it should be premised, are by no means to be regarded as characteristic of the disease, for the same qualities are found also in the blood of non-bleeders as a result of the extreme anaemia following pro- tracted hemorrhages. No correct inference, therefore, can be drawn in regard to the composition of the blood in bleeders, except from an examination of the fluid which escapes at the beginning of the hemorrhage, before it has undergone the typical changes belonging to acute anaemia (see Vol. XVI., p. 360). The number of exact analyses of such blood, as already remarked, is still far from large ; still, the gross examinations, such as could readily be made, have been sufficiently numerous to establish conclusively at least two important points : 1. The blood in bleeders at the outset of the hemorrhage is not paler in color than in healthy persons, but gradually becomes so as the hemorrhages continue, in consequence of the ensuing oligaemia. 2. The blood in bleeders maintains completely its coagula- bility for a long time during the hemorrhage, and does not acquire the above mentioned watery quality until late in the attack (Buel, Stoehr, Wachsmuth, Meinel, Assmann, and others). These results of the gross examination, pointing to the pri- mary absence of oligocythemia or hypinosis (deficiency of the blood in fibrinogenous and fibrinoplastic material), and probably also of a leucocytotic condition of the blood in bleeders, is, more- DESCRIPTION OF THE DISEASE. 45 over, supported by the few microscopical and chemical analyses that have been made (Heyland, Finger, Assmann, Gavoy-Ritter, Otto). These investigations show that the blood in haemophilia is not only not deficient in red blood corpuscles and fibrin genera- tors, but, on the contrary, contains an unusually large amount of these elements, and is, moreover, characterized by a compara- tive poverty in leucocytes. Such a conclusion, if confirmed by future observation, would certainly prove of great importance in reference to the theory of the disease, as demonstrating that the habitual condition of the blood in these individuals is rather one of plethora than of anaemia, and that the latter is merely a transitory accident of the disease. Assmann (Die Hemophilic Inaug. Diss. Berlin, 1869) in several cases carefully counted the red and white blood corpuscles under the microscope, and always found an absolute increase of the former, the relative proportion being as much as 1,500 to 1. A similar result had previously been obtained by Finger (Schmidt's Jahr- biicher. Bd. CXVII. S. 330). The excess of fibrin in the blood first effused was long ago noted by Heyland (Neue med. und chir. Zeitung. 1844. Nr. 5), who stated that he found per thousand parts 780 water, 137 coloring matter, 70 albumen, and 5 (!) fibrin. The latter figure seems suspiciously large, but an increase of fibrin has also been shown by the more recent analysis of Ritter, published by Gavoy is his disser- tation (L'Hemophilie. These inaug. de Strassbourg, 1861), as well as that by Otto (Ueber die Bluterkrankheit. Leipzig, 1865). I. Ritter. 1,000 parts of plasma contained : 1st Analysis. 2d Analysis. Water.................................. 923.20 922.44 Fibrin.................................. 2.64 2.64 Albumen................................ 73.90 74.70 Salts................................... 0.26 0.22 1,000.00 1,000.00 II. Otto. 1,000 parts of plasma contained : Water...................................... 905.04 Fibrin..................................... 4.35 (!) Albumen................................... 89.54 Fat........................................ 1.82 Soluble salts................................ 5.43 Extractives................................. 3.82 1,000.00 46 IMMERMANN.—HAEMOPHILIA. In the latter case—one of spontaneous epistaxis—a pound of the first blood lost was examined by Scherer's method. The specific gravity was 1,028, and nothing unusual was noticed in regard to the coagulation. After the cessation or arrest of an external hemorrhage the wound heals by different processes, according to the nature of the injury. Clean incised wounds usually heal rapidly by first intention (Otto, Buel, Elsaesser, Schulze, Uhde); still the resulting linear cicatrix shows for a time a marked tendency to reopen, and in this case another exhausting hemorrhage generally ensues. Irregular lacerated wounds, deep excoriations, and large surface wounds, on the contrary, very rarely heal by primary cicatriza- tion, but almost always by suppuration, during which pro- tracted process various secondary accidents are liable to occur, such as hemorrhages from the soft, generally fungous, and extremely lacerable granulations in the base of the ulcer, reten- tion and putrefactive decomposition of coagula'of blood in the wound, secondary gangrene, etc. (Dequevauviller, Thai, Uhde, Vieli, and others). Should, however, a cicatrix be ultimately formed in spite of these obstacles, its delicacy and great vascu- larity will involve a much greater danger of recurrent hemor- rhages than when the cicatrization has taken place by primary intention. Interstitial bleedings.—This variety of hemorrhage in bleeders, like the preceding, may occur either traumalically from pressure, a blow, or bruising of the parts, or apparently spontetneously, i. e., without any demonstrable injury. It is not improbable, however, that many of these so-called spontaneous interstitial extravasations are actually produced by mechanical injuries, which were of so trifling a nature as to have escaped attention. We have already seen that one of the chief peculiarities of the bleeder diathesis is the readiness with which trifling mechanical injuries give rise to very extensive ecchymoses, and it is not unreasonable therefore to suppose that in many of these appar- ently spontaneous cases we have really to deal with the effects of local injuries, the mechanical causes of which elude detection. By this remark, however, it is by no means implied that all interstitial hemorrhages in bleeders are of traumatic origin; on the contrary, there is every reason to suppose that they may DESCRIPTION OF THE DISEASE. 47 occur also, equally with the external hemorrhages, simply as a result of local congestions or of a general increase of the blood- pressure. Interstitial hemorrhages, particularly those of an undoubt- edly traumatic nature, belong in general to the earliest visible manifestations of haemophilia, since they frequently make their appearance during the first few days of life, or even during birth, from pressure or other mechanical injury of the body of the child during the act of parturition. In after-life, besides occur- ring as the direct result of injuries or as the effect of an antece- dent congestion and plethora, these interstitial bleedings are quite often noticed in connection with the external hemorrhages, both the traumatic and the spontaneous varieties. In this case the surface of the body very frequently becomes covered more or less universally with numerous hemorrhagic efflorescences indicative of the occurrence of multiple interstitial hemorrhages. The usual anatomical seat of the interstitial bleedings is the skin and subcutaneous connective tissue; in very rare instances also the autopsy has demonstrated their presence in the internal structures, e. g., the gastric mucous membrane and the brain (Schoenlein, Virchow). The cutaneous and subcutaneous forms, when produced traumatically, exhibit a special predilection for the back, fundament, the neighborhood of the trochanter and the back of the neck—in short, those parts of the body which are most subjected to pressure in consequence of the posture of the individual in sitting or lying, the wearing of tightly fitting gar- ments, etc. The spontaneous interstitial extravasations, on the other hand, are observed most frequently on the hairy scalp, the genitalia (particularly the scrotum), and the extremities; more rarely on the trunk and face (Virchow, Grandidier). According to the size and forms of the cutaneous interstitial hemorrhages or purpura-efflorescences, it is customary to distin- guish the several varieties by special terms ; thus, the dark, blu- ish-red, roundish spots of the size of the head of a pin or a lin- seed, are known as petechiae, those of larger size and irregular shape as ecchymoses, and the elongated eruptions as wheals or vibices. All of these varieties are met with in haemophilia as local 48 IMMERMANN.—HAEMOPHILIA. expressions of the existing hemorrhagic diathesis, and constitute the most frequent, if not the most.regular, symptoms of the dis- ease. It is to be particularly noted, moreover, that these inter- stitial cutaneous hemorrhages are met with far more frequently than the external bleedings (the traumatic as well as the non- traumatic) in those interesting rudimentary cases of haemophilia which are so commonly observed in bleeder circles, especially among the brothers and sisters of actual bleeders, or in the mothers of haemophilist sons (Grandidier), and which are there- fore to be regarded as manifestations of a family tendency to the disease (see p. 23). On the other hand, no one of these varieties of exanthemata is at all pathognomonic of haemophilia, since they all occur in other forms of hemorrhagic diathesis, in scurvy, in the morbus maculosus Werlhofii, etc. (see the two following chapters), and on the other hand are occasionally, though rarely, absent in genuine haemophilia. As regards their mode of origin, moreover, these purpuric eruptions present certain differences, which, although by no means of an essential character, are of sufficiently frequent occurrence to deserve mention. Thus, the larger interstitial hemorrhages, the ecchymoses and vibices, are particularly apt to originate traumatically; the wheals, in fact, being very often produced by pressure from the folds of tightly fitting garments upon the underlying skin, this pressure giving rise to linear extravasations, which form, as it were, impressions or copies of the individual folds of the dress. With respect to the other modifications in shape presented by the traumatic eruptions in bleeders, we have already noted a fact which has an impor- tant bearing in this connection, viz., that the size of the extrava- sation is almost always disproportioned to the force of the mech- anical injury, even the most trifling compressions or contusions of the skin being followed by hemorrhagic effusions of very con- siderable extent; hence, the hemorrhagic eruptions which are produced by obvious mechanical lesions are almost always of larger size and more irregular shape, and very rarely present the minute and regularly roundish form of the so-called petechiae. In regard to the origin of the latter, which are likewise (see above) of very common occurrence in bleeders, we can only say DESCRIPTION OF THE DISEASE. 49 that they sometimes make their appearance in large numbers quite suddenly and without apparent cause ; at other times they follow upon the profuse external bleedings, and in rarer instances they may be regarded as consecutive symptoms of congestive hyperaemias of the skin. While, moreover, the larger ecchy- moses, whether arising either traumatically or from congestion, do not appear to be connected, as regards their histological lo- calization in the cutaneous tissue, with any special sets of blood- vessels, the petechial bleedings, on the other hand, proceed chiefly from the close, delicate networks of capillaries, which sur- round the sweat-glands as well as the terminations of the hair- sheaths and sebaceous follicles, and form also the starting-points of small circumscribed interstitial hemorrhages in other hemor- rhagic forms of disease. The further course of the interstitial cutaneous hemorrhages is the same as is met with under other circumstances. The extravasated blood gradually undergoes certain typical changes : the red blood-corpuscles become deprived of their coloring mat- ter, shrink, and finally disintegrate ; a portion of the separated coloring matter is absorbed by the surrounding tissue, and the rest collects in the form of granules in the spaces between the tissue-elements, where it gradually changes in color. Corre- sponding to these metamorphoses in the effused blood, parallel changes of color take place in the hemorrhagic eruptions. When recent, the latter, as we have alreadjr mentioned, are of a bluish- red color ; later they become greenish, then brownish, yellowish, etc., and, as a rule, a considerable time (two or three weeks) elapses before they entirely disappear from the surface of the skin. The interstitial bleedings into the subcutaneous connective tissue are frequent, but by no means regular complications of the cutaneous hemorrhages. They are observed especially after injuries, but may also occur occasionally without an evidence of traumatism, apparently, therefore, spontaneously (Vieli). Clinically these subcutaneous hemorrhages are of much more serious import than the interstitial cutaneous bleedings, be- cause the effusion of blood usually takes place far more copi- ously into the loose coarse meshwork of the subcutaneous con- vol. xvii.—4 50 IMMERMANN.—HEMOPHILIA. nective tissue than into the denser and more homogeneous corium, and because the more or less extensive and prominent blood- tumors or ecchymomata (haematomata). which are produced by the subcutaneous hemorrhage, often become in their turn the source of further secondary disturbances. As regards their ana- tomical situation, these blood-tumors have been noticed most frequently in the region of the false ribs, on the back, and espe- cially on the lower extremities, tlie inner surface of the thighs, popliteal region, etc (Allan, Meinel, Martin, Grandidier, Lemp, Virchow, and others). In the reported cases the size of the tumors varied consider- ably ; many of them were as large as a goose egg or an apple, while several instances are mentioned of enormous ecchymoma- ta, as large as a child's head or larger, which had been produced by trifling contusions, or had apparently arisen spontaneously. The tumors, moreover, presented marked differences in resist- ance, many of them being as hard as a board, others soft and fluctuating ; frequently also the hard swellings ultimately became soft and distinctly fluctuating on palpation, or, on the other hand, even increased in density. These differences probably depend for the most part upon the location of the tumors, since in general the latter are soft or even fluctuating to the feel in those situations where the subcutaneous connective tissue is of a coarser texture and readily movable, and where therefore larger quantities of fluid or loosely coagulated blood can be effused into its interstices. On the other hand, the resistance of the tumor will naturally be much greater where the tissue is denser and possesses narrow meshes. In the latter case the original induration is modified in various ways by the subsequent changes which the extravasation undergoes (see below). The color of the blood-tumors is usually a bluish-black; they are generally, moreover, surrounded by quite a broad, rosy halo, which is evi- dently the result of a reactive inflammation excited by the effused blood, as is shown by the tenderness, which ma}7- even increase to severe pain, especially when pus has formed under- neath the skin. A frequent termination of these subcutaneous haematomata in bleeders is in secondary suppuration and ulceration of the DESCRIPTION OF THE DISEASE. 51 infiltrated tissue. When this result occurs, the originally hard and resistant tumor becomes soft and fluctuating, usually first over its central portion ; the skin becomes thinned, and external rupture takes place either spontaneously or from some accidental or intentional traumatic lesion. The discharge is almost always composed, in addition to pus and shreds of tissue, of a large quam tity of blood, and is generally followed by a very obstinate and copious external hemorrhage. The rupture or opening of a sub- cutaneous blood-tumor in a bleeder is evidently, therefore, always attended with risk, and at times with urgent danger. Another source of danger is the occurrence of dry gangrene of the skin covering the tumor, or of sloughing of the infiltrated connective tissue before or after the opening of the haematoma. In both of these conditions, especially the latter, a profuse intercurrent hemorrhage is to be apprehended from the erosion of small vessels. In many cases, on the other hand, these blood-tumors run a more favorable course : no rupture occurs from any of the previously mentioned causes, but the effused blood is gradually absorbed, and the tumor, after becoming softer, but still not fluctuating, finally disappears entirely. Still, the process of involution requires months for its completion, and during this time slight mechanical injuries not infrequently excite renewed interstitial hemorrhages, and a more or less complete restoration of the original size of the tumor. Other symptoms of haemophilia.—We have already described so fully the essential clinical features of the disease while con- sidering the haemophilia bleedings, that little is wanting to com- plete the picture. Aside from the existing hemorrhagic diathesis and the intercurrent constitutional disturbances produced by it, there is usually little in the general condition of these patients that is actually abnormal, or even specially characteristic. Their bodily functions, digestion, respiration, the urinary and other secretions, are frequently performed with entire regularity. Exceptions to this rule have, to be sure, been often observed, and disturbances of various kinds have been described in reference to this or that particular function ; still it seems to be entirely clear from the data we possess that these individual differences are either merely -physiological peculiarities of the constitution such 52 IMMERM ANN.—HEMOPHILIA. as are met with in perfectly healthy individuals, or else, patho- logical accidents, which have no direct connection with the haBmophilia itself. The reader is referred, therefore, for what- ever further information he may derive on any of these points, to the original articles (see Bibliography). There are, however, on the part of the organs of circulation, certain pathological phenomena which are of such constant occurrence in this affection as to be of special significance. These symptoms, which may be briefly characterized as congestive or even &s plethoric, have been already referred to in the etiolog}^, and again just now in our consideration of the bleedings, for the reason that the abnormity in the circulation or quantity of blood which these symptoms denote is probably not without an impor- tant determining influence upon both the occurrence of the spon- taneous and the course of the traumatic hemorrhages. In the chapter on the Nature of the Disease we shall consider this point more fully, but we may here add that these signs of increased arterial tension and plethora (violent beating of the heart, a full, hard arterial pulse with fulness of the visible veins, flushed appearance, sensation of heat, headache, giddiness, mental excite- ment) are not only observed very frequently as prodromata for some time previous to the spontaneous bleedings, but also still more frequently make their appearance and gradually disappear again without the production of hemorrhage. Such, briefly, is the part which these symptoms are observed to play in the eti- ology and symptomatology of haemophilia ; the consideration of their further causal relation to certain frequent complications and sequelae of the disease must be deferred to a later chapter. Anatomical Changes. The total number of autopsies made thus far upon the bodies of bleeders is perhaps as large as might have been expected in view of the comparative rarity of the disease ; still, so few of even this small number have been conducted with the necessary care and thoroughness, that it certainly seems premature at present to speak of certain patho-anatomical conditions as if they were constant anomalies of the bodily organization in ANATOMICAL CHANGES. 53 bleeders. The few results that have been obtained are, however, sufficiently important to deserve full consideration, especially as they seem to throw some light upon the deep obscurity which otherwise involves the nature of the entire affection (see below). Should future autopsies reveal with more and more frequency the existence of conditions similar to those to be presently described, we would then have a definite patho-anatomical basis for a rational interpretation of the clinical phenomena in many cases of haemophilia. It is probably scarcely necessary to show here in detail that many of the changes which have been repeatedly found at these autopsies are by no means to be regarded as anatomical causes of the bleeder diathesis, but rather merely as results or acci- dental complications which have no necessary connection wTith the disease itself. The purely accidental changes need not detain us, while as regards the simple con- secutive lesions it need only be remarked, that when the death had resulted from traumatic hemorrhage, the body naturally presented traces of the wounds ; further- more, that petechiae, ecchymoses, and blood-tumors were observed in cases which had presented these symptoms before death; and finally, that as the fatal result had in most cases been occasioned by loss of blood, there were generally to be observed the usual cadaveric signs of the intense anamia, viz., extreme decoloration of all the external and internal parts, a minimal quantity of blood everywhere in the body, and a pale, watery condition of the residual blood. No apparatus of the body seems to be abnormally affected in bleeders so uniformly as the vascular system (Virchow). Both the older and more recent writers speak of the striking superficiality and abnormal distribution of the cutaneous and subcutaneous veins and arteries, and especially of the abnormal structure and width of the arteries (Blagden, Schoenlein, Schlie- mann, Liston, Wilson, Hooper, Fischer, Virchow, Grandidier, Gavoy, Uhde, Schuenemann, 11. cc). Thus, in quite a large series of cases, the intima of the smaller and larger arteries (the tem- poral and radial, the aorta, pulmonary, carotid, etc.) was found to be remarkably thin, and sometimes actually transparent, without any apparent diminution, however, in the elastic retrac- tility of the coats of the vessels (Virchow) ; while in a certain number of these cases the lumen of the large arteries (aorta, pulmonary) and their main branches was abnormally narrow throughout the entire extent of the vessels (Schliemann, Vir- 54 IMMERMANN.—HEMOPHILIA. chow, Uhde). Very generally, also, where the autopsy was carefully made, the intima of both the large and the small arteries was distinctly seen to have undergone a partial fatty degeneration quite analogous, as regards its locality and other characters, to the degenerative changes of the inner coat of the vessels in anaemia and chlorosis (Vol. XVI., pp. 358 and 530). The subject is one of such great importance that it is only proper to complete the above general sketch by citing a few reports of the results found in particular cases of the disease. As early as the year 1817, Blagden, on ligating the temporal artery in a bleeder twenty-seven years of age, found that its coats were as thin as those of a vein; at the subsequent autopsy a similar condition was detected in other branches of the external carotid, and in this vessel " there were several opaque white depositions on the outer surface of its inner coat, such as precede ossifica- tion " (fatty degeneration, according to Virchow ')• A similar condition was found by Hooper (1840) in the radial arteries, as well as- in other vessels of the arm, in a bleeder twenty-five years of age, who had bled to death from a slight contused wound in this region, occasioned by a fall from a horse.— Wilson (1840)2 found the walls of the arteries in a bleeder child three and a half years old, only half as thick as normal, and Fischer (1855) also found the coats of the arteries extremely thin and transparent in a bleeder aged eighteen. Previous to this, in 1831, Schlie- mann published a case observed by Schoenlein, in which the pulmonary artery of a bleeder fifteen years old was observed to have unusually thin walls and an abnormally small calibre. Narrowing of the pulmonary artery was also noticed sub- sequently by Gavoy (1861) at the autopsy of a bleeder fourteen years of age. Far more frequently the aorta has been found to be narrowed ; at least, Virchow in his treatise on chlorosis,3 while describing the vascular lesions of that affection, men- tions also that he has met with this defect of growth in almost all the autopsies made by him on bleeders since 1857, when his attention was first called to it by a striking case of haemophilia reported by Lemp—a man twenty-four years of age, with an enormous hsematoma of the right thigh. It is probable, therefore, that this arterial hypoplasia, together with the partial fatty change which generally accompanies it, is by no means peculiar to severe forms of chlorosis, but likewise bears a specific relation to haemophilia, of which it frequently seems to constitute the anatomical substratum. As regards the condition of the heart, our information is less definite. To be sure, most of the recent reports of autopsies 1 1. c. p. 268. 2 This date is incorrect. The case is related in Wilson's Lectures on the Blood, etc. London, 1819. p. 412.—Translator's Note. 3 Ueber die Chlorose und die damit zusammenhangenden Anomalien im Gefassappa- rate u. s. w. Berlin, 1872. COMPLICATIONS AND SEQUELAE. 55 mention a fatty degeneration of the musculature of the organ; but, in view of the extreme anaemia of the cadaver in the majority of cases, it seems to be altogether probable that the lesion in question is merely the anamic form of fatty heart (see Vol. XVI., p. 358). The size of the heart is reported in some cases as normal (Elsaesser), more frequently as hypertrophic ; the lat- ter condition sometimes involving the entire organ (Gavoy), but generally only the left ventricle (Besserer, Schneider, Virchow). The absence, however, of any definite mention of the size of the heart in many other cases, particularly in the older reports, leaves it still doubtful whether a moderate degree of hyper- trophy is a frequent or only an exceptional lesion in bleeders. Should the former prove to be the case on future investigation, the cardiac enlargement would naturally fall into line with the abnormal position and structure of the vessels as one of the determining conditions of the symptoms of haemophilia (see later, the Nature and Pathogenesis of the disease). As regards other organs, the lesions observed have been so various in character as to require no special mention, with the exception, perhaps, of the spleen, which has sometimes been found to be enlarged, softened, and engorged with blood, as com- pared with the other organs (Schultz, Uhde, Spalm, Buss). In the great majority of cases, however, no such changes were ob- served, and it is more than probable, therefore, that the enlarge- ment of the spleen found in the instances referred to was merely an accidental complication of no importance in the genesis of the haemophilia. Complications and Sequelae. The disposition to other diseases does not appear to be essen- tially different in bleeders from that of healthy individuals; at least we find it mentioned in many of the reports that the patients suffered, equally with non-bleeders, from the most va- rious acute and chronic local and general affections, which appar- ently stood in no genetic relation to the habitual hemorrhagic diathesis. These accidental complications, it is interesting to observe, do not in general seem to run a more unfavorable course 56 IMMERMANN.—HAEMOPHILIA. in bleeders than in others, unless the complications are of such a nature as to excite the intercurrence of haemophilia bleedings (Grandidier). In brief, therefore, it may be said, as regards the majority of other affections, that the existence of this diathesis does not noticeably predispose to their occurrence, affords no marked immunity from them, and does not appear to materially modify their results. Whether bleeders and their immediate non-bleeder relations are really less liable than other persons to consumption (Grandidier) must, in the absence of exact statis- tics, still remain doubtful. At all events, the immunity is not absolute, for well- authenticated cases of fatal phthisis have been reported in bleeders and their relations (Bjorkmann and Lindbeck, Finger, Lindwurm, Schmidt). Just as all kinds of acquired morbid processes arise and run their course independently alongside of this permanent diathe- sis, so haemophilia may- be occasionally complicated also with other diathetic affections, which from time to time produce their characteristic derangements of health. Thus, combinations of haemophilia with scrofula have been repeatedly observed (Schlie- mann, Lindwurm, Reinert, and others), and in other cases gouty attacks are mentioned ; still these instances form so small a frac- tion of all the cases of haemophilia, that there does not seem to be even the remotest justification for regarding these complica- tions as anything more than mere "accidents," for which the bleeder diathesis is in no way responsible. On the other hand, some few affections are encountered in connection with haemophilia so regularly, or at least with such striking frequency, that we cannot but regard them as more or less dependent upon the affection in question. This is obviously the case with the acute general anaemia which ensues after each of the bleedings, and which, from its natural connection with the hemorrhages, might with equal propriety be classed either with the symptoms or with the complications of haemophilia. We prefer, however, to include it under the latter head for two rea- sons : first, because, until the blood-mass is completely restored, the anaemia modifies the usual bodily condition of the patient so essentially as to become itself the object of separate attention and treatment; and secondly, because, upon theoretical grounds COMPLICATIONS AND SEQUELAE. 57 to be considered later, it seems to us particularly desirable that the symptoms which belong to the haemophilia per se should be distinguished fundamentally from those of the consecutive intercurrent anaemia. The so-called rheumatic affections are also of such frequent occurrence in bleeders and their immediate relations as to de- serve mention in this connection. In fact, Grandidier, while he regards these attacks as " pseudo-rheumatic " in character rather than as belonging to "true " rheumatism, mentions them among the s37mptoms of haemophilia in direct connection with his de- scription of the external and interstitial bleedings. That painful swellings of the joints, muscular pains, and also neuralgic at- tacks, particularly violent toothache, are of extremely common occurrence, not only in actual bleeders, but also in their non- bleeder brothers and sisters, can certainly no longer be disputed, since the number of bleeder families in which these rheumatic or pseudo-rheumatic affections occur in a cumulative manner is already quite large and is steadily increasing. To include these attacks, however, among the symptoms proper to haemophilia, or to designate them, as Grandidier has done, by a term which distinguishes them from true "rheumatic" processes, seems to us at present of doubtful propriety, for the reason that they are met with in only a minority of cases, and moreover are identical, so far as their mode of occurrence and general course is con- cerned, with the ordinary forms of rheumatism. For these reasons we have preferred to consider them among the complica- tions of haemophilia, and to regard them as an indirect rather than as a direct effect of haemophilia, leaving to the future the determination of the real nature of the causal nexus. As far as we can ascertain, rheumatic affections of the above general character have thus far been observed in the members of eighty-two bleeder families. This number, although quite large, is still too small in comparison with the total num- ber of bleeder families to warrant us in regarding these attacks as immediately dependent upon the bleeder diathesis. The most important of these rheumatic diseases in bleeders are unquestionably the joint affections. These comprise all grades of arthritic rheumatism, from simple inflammatory arthralgia up 58 IMMERMANN'.—HAEMOPHILIA. to the most copious synovial effusions. The attacks appear to occur most frequently during the cold, damp weather of spring and autumn (Vieli, Grandidier); sometimes they are preceded, like the spontaneous bleedings, by various symptoms of conges- tion ; at other times they occur without any prodroma what- ever. Their relation in point of time to the bleedings is by no means typical, since they may precede, accompany, or follow the latter. In many cases their development is quite acute, at other times slower and more gradual ; in the former case febrile symptoms usually occur in addition to the articular pains, in the latter there is usually an absence of fever. The course of those attacks, in which the pain is a more prominent symptom than the effusion, resembles, or is identical with, that of so-called acute articular rheumatism. Thus, in many of the cases the pains occur in several joints simultaneously, alternately decline and increase again in intensity, or migrate from one joint to another. Sometimes, however, the pain is confined for some time to a single joint, which in certain cases may also present the signs of fluid effusion. These effusions are usually serous, but it is probable that they may also be sometimes of a sanguinolent character, at least it is so stated by Dubois, Camman, and Ass- mann. In the latter case the effusion is clearly to be regarded as a direct symptom of the haemophilia, in the same sense as the internal superficial hemorrhages of bleeders. Whether extrava- sations of blood ever take place into the cavities of the joints in these patients cannot be determined with certainty in the absence of any autopsical results upon this point. In the reported cases of this kind the diagnosis has rested merely upon clinical symp- toms, such as the greater painfulness of the swollen joint, the pressure of cutaneous hemorrhages in the neighborhood, and the palpatory evidence of solid masses in the fluid effusion, which were supposed to be coagula of blood. Still, these cases have been decidedly exceptional ; far more frequently the symptoms have all pointed simply to a serous effusion, viz., more or less swelling of the joints, moderate pain on forcible pressure, or even an entire absence of pain, and usually on careful exploration the evidence of fluctuation. The termination of most of the reported cases has been in COMPLICATIONS AND SEQUELAE. 59 recovery, with a gradual or rapid subsidence of the pains in the painful forms, or with absorption of the fluid effusion in the exu- dative affections of the joints. In many of the latter cases the attack appeared to be followed by considerable thickening of the synovial membrane, as well as by thickening and shortening of the accessory ligaments, resulting in permanent anchylosis. This unfortunate result was noticed most frequently in the knee, but exceptionally also in other joints (elbow, hip). Suppuration of the joints, on the other hand, has never been observed in these affections as a result of the inflammatory process. The rheumatic muscular affections in bleeders completely resembled, in their clinical features, the ordinary forms of rheu- matic myalgia. They occurred still more frequently than the joint affection, and very often were superadded to the latter. As regards its mode of occurrence, duration, and localization, the muscular affection was far from presenting any uniform or typical character; on the contrary, the greatest diversity in these respects was observed in the individual cases. The usual termina- tion was in recovery, i. e., disappearance of the pain and com- plete restoration of function ; in some instances, however, proba- bly in consequence of proliferation of the interstitial connective tissue and subsequent* contraction of the latter, the chronic rheumatic myositis finally resulted in permanent contracture and consecutive atrophy of the affected muscle. The neuralgic attacks of bleeders seem to affect most fre- quently the dental branches of the trigeminus. Thus, Grandidier mentions the striking frequency with which bleeders suffer from periodic attacks of violent toothache, often independently of any obvious cause such as caries. As experience has amply proved, there is great risk in these cases that the patient, in spite of all warnings, will insist upon the extraction of one or more teeth, an operation which is followed usually by dangerous, and sometimes by actually fatal hemorrhage from the lacerated vessels of the alveoli. In concluding our consideration of the complications of haemo- philia, it may be added that the rheumatic disposition not only occasionally outlasts the tendency to hemorrhages, but in some 60 IMMERMANN.—HAEMOPHILIA. instances does not make its appearance until after the extinction of the latter, and then is entitled to be regarded rather as a sequel than a complication of the disease (see Duration, Termina- tion, and Prognosis). Little is known in regard to other sequelae, partly because many bleeders die at a very early age from the direct effects of the disease, partly also because the affection in others persists into old age, and finally because the number of complete and incomplete cures of the bleeder disposition, notwith- standing all the cases that have been reported, is still compara- tively small. We merely remark, therefore, that besides the purely accidental affections noticed in these persons after the subsidence of the hemorrhagic disposition, in some cases moist eruptions on the head, and in others hemorrhoids, are mentioned as making their appearance so immediately after the disappear- ance of the haemophilia, that some observers have preferred to regard these complaints as critical manifestations of the disease, or perhaps even as anomalous symptoms of a still existing, but latent, bleeder diathesis. Nature and^ Pathogenesis of Haemophilia. In the foregoing remarks on the etiology, symptoms, anatom- ical changes and more important complications of haemophilia, we have endeavored to present the reader with a brief account of the known facts so far as they are externally related to each other; the question now naturally arises, what is the causal nexus between these empirically ascertained facts, or, in other words, how are we to interpret the nature and pathogenesis of this remarkable affection ? At the very outset of this article we were obliged to confess that all the hypotheses and theories advanced hitherto in reference to the nature of the bleeder disease—even the most recent and best established of them not excepted—are still very defective, and by no means suffice to bring the observed symptoms into complete accord with the post-mortem results and etiological facts. But none of these hypotheses fail so completely to meet the requirements of modern pathology as those which, without attempting to account for the clinical and anatomical facts of the disease, and without any evidence but a fancied NATURE AND PATHOGENESIS. 61 resemblance, simply assert the relationship or even identity of haemophilia with other more or less imperfectly understood constitutional anomalies. To this category belong some of the older views of the affec- tion, which have long since been abandoned, and now possess merely an historical interest. According to these, haemo- philia was supposed to be, properly speaking, not an inde- pendent disease, but merely an exceptional expression of morbid bodily conditions, which ordinarily manifested themselves under other and what might be regarded their legitimate clinical forms. Thus, Krimer assumed that haemophilia is identical in its nature with the congenital arthritic dyscrasia, of which he supposed it to constitute merely a special variety ; while, on the other hand, Schliemann regarded it as a particular modification of scrofula. These hypotheses were based simply upon the obser- vation of cases in which bleeders had suffered from gouty attacks later in life, or had presented symptoms of scrofula in addition to those of haemophilia, without there being any plausible reason whatever for inferring an essential connection between the two classes of symptoms, and in spite, moreover, of the well-known fact that the majority of bleeders do not suffer from gout or scrofula, and that the majority of gouty and scrofulous individuals are not subjects of haemophilia. Still more arbitrary was the assumption of Heyfelder, who united these two opposing doctrines into a single theory, according to which the underlying constitutional anomaly of haemophilia was held to be a combination of hereditary arthritis and scrofula. This view, which we have mentioned merely for the sake of completeness, may be left to the refutation which a simple state- ment carries with it. Far more plausible is the view entertained by some other writers (Vieli, Grandidier, Hyde-Salter, et al.), that there is a close relationship between haemophilia and the rheumatic dis- position. This opinion was based upon certain facts, to which we have already alluded in the preceding chapter, viz., that a very large proportion of all the hitherto observed cases of haemo- philia suffered at some period of their lives, either during the continuance of the hemorrhagic diathesis or after its disappear- 62 IMMERMANN.—HAEMOPHILIA. ance, from so-called rheumatic attacks (painful affections of the joints, muscles, etc), and that, furthermore, the same symptoms have been noticed also to occur in a strikingly cumulative man- ner within the circle of many bleeder families. AVere the question merely one of relationship, and not of identity, between the two forms of disease, the above view might be accepted without much hesitation, since there can be no question that bleeders as a class exhibit a marked predisposition to rheumatic affections. But we fail to see any good reason for regarding haemophilia as simply a special form of rheumatism. In the first place, rheuma- tism in both its hereditary and acquired form is far more fre- quently met with clinically as an entirely independent disease wholly unconnected with haemophilia, and, therefore, in all probability rests upon a much wider etiological basis than does the latter affection. Furthermore, the rheumatic affections in question are by no means universal in bleeders, nor is rheuma- tism common to all bleeder families ; it seems fair to conclude, therefore, that the two pathological territories are not only unequal in extent, but overlie each other so partially that there is no warrant for their fusion into a common domain. Still, even if we restrict ourselves to the view which appears upon the whole to accord best with clinical experience, viz., that the connection between the two affections is merely that of family relationship, manifesting itself in the fact that the fundamental structural vice of haemophilia operates also as a predisposing factor for the development of rheumatic processes, we gain very little after all towards a comprehension of the nature of the bleeder disease, so long as the nature of rheumatism is itself so imperfectly under- stood. While we admit, therefore, that the frequent coincidence of rheumatic symptoms with haemophilia is a fact of great clini- cal interest, and may possibly help us at some future day to a correct understanding of the nature of both diseases, we fully agree with Virchowx in his warning against the folly of attempt- ing to explain one unknown subject by means of another equally obscure. The marked hemorrhagic character of the symptoms of haerno- 11. c. p. 269. NATURE AND PATHOGENESIS. 63 philia has naturally led also to various attempts to connect the disease with other forms of the hemorrhagic diathesis. Thus, J. Vogel has maintained the identity of haemophilia with scorbu- tus ;' while Virchow at one time insisted that haemophilia might possibly be closely related to chronic splenic cachexia,3 but latterly seems to have entirely abandoned this opinion. If haemophilia, however, as we had occasion to point out at the very beginning of this article, can properly be made to include only the congenital and habitual cases of hemorrhagic diathesis, together with such briefer and more tardy forms of hemorrhagic disease as are clearly connected genealogically with undoubted bleeder cases, then certainly the view which associates haemophilia with other hemorrhagic affections must be regarded as absolutely untenable. In confirmation of this view we may note also the important fact that the severe general cachexia, which scorbutic patients present in addition to their hemorrhagic diathesis, and which is noticed also in those splenic affections during the course of which a tendency to bleedings is developed, is entirely for- eign to haemophilia per se ; in fact, it is just the contrast between the general good health and the existing disposition to dangerous hemorrhages which is one of the chief characteristics of bleeders. Finally, the theory of a close relationship between haemophilia and the hemorrhagic splenic cachexia is disproved by the cir- cumstance that while the spleen has been found somewhat enlarged at a few autopsies of bleeders, in the great majority of instances no mention is made of any tumor of the organ. The attempts to trace the origin of haemophilia to the spleen were evidently determined by two considerations : on the one hand, by the recognized fact that this organ is intimately con- nected with the formation of the blood, and on the other, by the belief that the nature of haemophilia consists in a defective composition of the blood. Before Virchow gave to this belief a somewhat more concrete expression by pointing out the possibly splenic origin of the supposed alteration of the blood, a variety of views as to the nature of this defect were entertained by the older writers. Thus, some supposed it to consist in a retention 1 Handbuch zur Kenntniss und Heilung der Blutfliisse. - 1. c. p. 209. 64 IMMERMANN.—HAEMOPHILIA. of the blood at its embryonic stage of development (Meckel), and others in a deficiency of fibrin and red blood corpuscles (hypi- nosis and oligocytliaemia rubra).' The untenableness of these theories, however, ultimately became apparent, when it was proved by Wachsmuth, Besserer, Meinel, and others, that the blood in bleeders is by no means defective either in its organiza- tion or composition, and that when care is taken to collect and test the first blood which flows, the latter is found to coagulate readily and to be no lighter in color than usual. The careful microscopic and chemical analyses made still more recently (see p. 45), all show conclusively that the blood in haemophilia actually contains more than its normal share of fibrin and red blood corpuscles, and in other respects completely resembles normal blood ; so that, for the present at least, the hypothesis that the bleeder disease is in general dependent upon a congenital imperfection of the blood, or is a dyscrasic affection, will have to be entirely abandoned. In thus rejecting all dyscrasic theories of haemophilia, we by no means wish to be understood, however, as denying the occur- rence of accidental changes in the blood, but only as insisting that these are to be considered merely as casual complications, or as consecutive disorders incident to the disease. Under the latter head we have in mind particularly the very intense acute oligaemia which so frequently develops inter currently as a necessary result of the hemorrhages, and which, should the hemorrhage prove fatal, is encountered at the autopsy along with the other consecutive lesions. That this purely secondary alteration of the blood can in no wise be held responsible for the morbid disposition—the primary disease—is so perfectly obvious that this renewed allusion to the subject might seem entirely superfluous ; still we deem it necessary to again call attention to it expressly, because this secondary oligaemia of bleeders, like every other intense oligaemia, determines in its turn, through a sort of vicious circle, the production of conditions which not only protract the continuance of the immediately existing hemorrhage, but also in a special manner favor the occurrence 1 Nasse, Elsaesser, and others. NATURE AND PATHOGENESIS. 65 of new hemorrhages in other localities. For, the more watery (hypinotic) the blood becomes in consequence of the progressive loss of blood, the more unfavorable will evidently be the con- ditions for the spontaneous arrest of the external hemorrhages by the formation of a clot upon the bleeding surface. Further- more,-the greater the diminution in the stock of the red blood corpuscles, the greater the danger of the development of a sec- ondary hemorrhagic diedhesis, induced by the defective func- tional restitution and impaired nutrition of the walls of the vessels (see the articles on Anaemia, Chlorosis, and Progressive Pernicious Anaemia, in Vol. XVI., particularly pp. 358, 530, 585). In this way the temporary oligaemia occasioned by loss of blood, besides materially promoting the persistence of the primary bleeding, in all probability also determines the occur- rence of those secondary hemorrhages, which, in the form of petechial superficial hemorrhages from mucous membranes, etc., so frequently accompany or follow the true (primary) bleedings of haemophilia.—Strictly speaking, therefore, it does not seem to us quite correct to regard these secondary hemor- rhages as heemoph ilia bleedings, notwithstanding the fact that they occur in bleeders, and are, equally with the primary bleed- ings, the expression of a hemorrhagic diathesis ; on the contrary, they appear to be completely analogous to the hemorrhagic attacks which occur also in non-bleeders as a result of intense oligocythaemia from any cause, and are therefore to be regarded as merely the clinical manifestations of a transitory disposition to hemorrhages only very indirectly connected genetically with the congenital and habitual hemorrhagic diathesis of haemo- philia. Besides the above-mentioned secondary hemorrhagic diathesis, we certainly ought to include also, among the results of the symptomatic oligaemia of bleeders, the degenerative changes so frequently found at the autopsy in the muscular sub- stance of the heart, the intima of the vessels, etc., because exactly the same lesions are constantly met with in other cases of intense anaemia, particularly in those of a progressive pernicious character (see the articles referred to above), and are obviously, therefore, not directly due to the haemophilia itself. To attach impor- tance to these probably often quite terminal degenerations, in connection with the occurrence of the primary bleedings, as if the vascular degeneration had been an original and continuously acting predisposing cause of rupture of the vessels, seems VOL. XVII.— 5 66 IMMERMANN.—HAEMOPHILIA. to us therefore highly objectionable. Indeed, it is at once clear, from the very nature of haemophilia as a congenital and persistent hemorrhagic diathesis, that the underlying anatomical cause must itself also possess the character of a preformed and at the same time stationary anomaly. But what now is this enigmatic pathological something which is to be regarded as the true cause of the bleeder anom- aly, and of which we have thus far been able to predicate only that it is probably not of a dyscrasic nature '. Is haemo- philia at all a patho-anatomical unit, in the sense that invari- ably, in every individual case of the disease, an anatomical abnormity recurring in a stereotyped form can be demonstrated, which is capable of explaining the congenital and habitual hemorrhagic diathesis of the persons affected by it i We have already intimated repeatedly that this does not appear to be the case ; that, at least so far as our knowledge extends at present, haemophilia is not yet to be regarded as an anatomi- cal, but merely a clinical pathological unit, because a com- parison of the total autopsical results shows that there is no single anatomical characteristic common to all the cases ; that, in fact, even the changes most uniformly encountered are in some instances entirely absent. Any attempt, therefore, to explain the nature of haemophilia upon the hypothesis that all cases of the disease are anatomically identical, in the same sense as all cases of croupous pneumonia, tj^phoid fever, etc., are supposed to be identical, will, in our opinion, necessarily prove a failure, so that all that can be attempted at present is to apply the positive results in particular autopsies to the interpre- tation of the haemophilia in concreto. By far the most readily susceptible of at least a partial, if not a complete, explanation of the clinical complex of symp- toms, is that entire class of cases of congenital and habitual hemorrhagic diathesis, in which the autopsy has revealed the existence of evnomedies in the position of the cutaneous and sub- cutaneous vessels, particularly an unusually superficial course of the same, as well as certain, probably equally congenital, structural changes in the arteries, especially a striking delicacy of their wcdls and an abnormal narrowness of their lumina. Moreover, the recent observations of Virchow have shown that NATURE AND PATHOGENESIS. 67 in all probability this class or group includes by far the majority of cases of the disease, so that, if we are able to give some sort of anatomical explanation of the bleeder diathesis in these cases, we shall have taken an important step forward upon this difficult ground. In fact, Virchow, whose earlier but recently abandoned views have been referred toabove, is now inclined to maintain a leading role for these vascular anomalies in the production of the symptoms of haemophilia, and in his discussion of the similar lesions occurring in chlorotic individuals has attempted incident- ally, and, of course, only in brief outlines, to sketch a mechanical explanation of the bleeder disease upon this basis. In the fol- lowing brief presentation of the subject it will be our object to describe somewhat more fully the influence of these vascular abnormities upon the conditions of the circulation, and to throw what light we can upon the manner in which th& lesions in question predispose to the occurrence of the bleedings of haemo- philia. At the same time, however, it should be premised that the views advanced here apply only to a certain proportion of all the cases of haemophilia, i. e., only to those in which the vascular anomalies actually exist, and that even for these cases the explanation is incomplete. In order to account fully for the clinical facts, we are compelled therefore to call in the aid of further auxiliary conditions, which cannot, it is true, be demon- strated with the same precision as the vascular anomalies, but may yet be inferred with the highest degree of probability from certain symptoms during life. These auxiliary conditions, the diverse character of which renders their existence in individual cases for the present merely conjectural, will also require to be considered in some detail, partly for the purpose of filling up logically the numerous gaps which the vascular theory still leaves in the explanation of the above cases, and partly because instances repeatedly occur in which, on account of the absence of demonstrable vascular anomalies, these supplementary con- ditions are our sole guide to the elucidation of the affection. Before entering upon the subject of the auxiliary conditions, let us first consider the influence of the vascular anomalies them- selves, and inquire in what manner each of them, considered by itself, promotes the occurrence of the bleedings of haemophilia. (58 IMMERMANN.—HAEMOPHILIA. Now, the most important clinical features by which these hem- orrhages are characterized, it will be remembered, are : 1. The readiness with which they are excited. 2. The force with which the blood escapes. 3. Their protracted duration and obstinacy. The question before us. therefore, is how far can the superfi- cial position, the delicacy and the narrow lamina of the, vessels; favor the occurrence of hemorrhages in general, and how far can they, in an already existing hemorrhage, give it an unusually violent and obstinate character''. Now, in the first place, a supnficietl position of the cuta- neous and subcutaneous vessels evidently exposes the latter more intensely and more frequently to all kinds of mechanical injuries, and therefore undoubtedly predisposes to the occur- rence of both superficial and interstitial traumatic hemorrhages in all individuals affected with this topographico-anatomical anomaly. The same result may be brought about also by means of the fluxions, which the anomaly facilitates to a high degree in the capillaries of the general integuments of the body (the skin and subcutaneous connective tissue). For a diminished thickness of these tissues not only exposes the superficial arte- ries in an exceptional degree to all those numerous external influences which are known to be capable of inducing arterial hyperaemia (e. g., mechanical, chemical, thermal influences, etc.), but it also opposes a lessened resistance to the expansion of the vessels by the forcible entrance of blood in fluxions from inter- nal causes (e. g., plethora sanguinis, violent action of the heart, etc.). But whenever such a determination of blood takes place in the superficial arteries, an overdistension and increased blood- pressure must necessarily arise also in the capillaries, and thus predispose not only to extravasations in general, but especially also to those of an unusually profuse and protracted character. In a similar manner the thinness of the walls of the arterial vessels also predisposes to hemorrhagic attacks in general, and to a more malign course of the same in particular. Not only does this delicacy of structure facilitate the occurrence of traumatic lesions in the superficial arteries from external injuries, but more especially it also increases the liability to active congestions from NATURE AND PATHOGENESIS. 69 both external and internal causes. AVith the same distending force a thin arterial wall will naturally expand more consider- ably than a thick one, and consequently equally energetic contractions of the heart will be more likely to produce an engorgement in a vascular apparatus provided with thin walls as a result of the diminished resistance to the circulation, than in vessels more solidly constructed. The immediate result of such a distension of the arteries, provided the coats of the vessels retain their elasticity, will evidently be to propel the blood more forcibly into the capillaries in direct proportion to the arterial expansion by the systolic blood-waves. Now, at most of the autopsies of bleeders the arteries, even the largest, such as the pulmonary artery and aorta, have been found to present just these characteristics, viz., an abnormal thinness, together with a considerable degree of elasticity of the walls (Virchow), and it is fair therefore to conclude that during the life of these cases the entire capillary blood was at all times subjected to a compara- tively high pressure, which might not only have favored the occurrence of hemorrhagic attacks, but also at the same time have impressed upon the latter the special character of haemo- philia bleedings. As regards, finally, the influence which an abnormal narrow- ness of the large eirteries, particularly the aorta, exerts upon the circulation, we may conveniently refer to our exposition of the subject in the article on Chlorosis (Vol. XV L, p. 539), where the subject was discussed at some length on account of the very important part which this particular anatomical anomaly (in con- nection with an increased delicacy of the arterial walls) plays also in the latter affection. The reader of that article will remem- ber that while the clinical picture of arterial hypoplasia varies considerably in different individuals, according to the quantity of blood and the degree of elastic retractility possessed by the coats of the arteries, the anomaly in question, under some cir- cumstances and in a certain proportion of the cases, presents the character of a fluxionary diathesis with a tendency to profuse hemorrhages. This will be the case particularly when, in addition to a retention by the vessels of their natural elasticity, there is also an excessive volume of blood in comparison with the diminished 70 IMMERMANN.—HAEMOPHILIA. width of the arterial apparatus (Virchow). Now, just as the menorrh.agic type of many cases of chlorosis, as distinguished from the more common amenorrhceic form, may probably be accounted for by such a so-called plethora ad vasa (or plethora ad spatium), so also a sort of explanation would be afforded for the occurrence of haemophilia bleedings and for the existence of a more or less permanent hemorrhagic diathesis in certain indi- viduals with a narrow arterial apparatus, if it could be shown with sufficient certainty that the blood-supply in these persons is habitually in excess of the capacity of the vessels ! A direct estimation of the volume of blood in bleeders during life has never been attempted, and is of course impracticable; while, as we have seen, the amount of blood found after death is usually no guide as to the quantity present during life. Although it is impossible, therefore, to prove directly (by measurement of the volume of blood) that a condition of plethora ad vasa exists in many or all cases of haemophilia, still some of the clinical symptoms, it seems to us, point clearly to the great plausibility of such an hypothesis. Of these clinical indications we need enumerate only : 1. the peculiar congestive symptoms which so frequently precede by a shorter or longer time the spon- taneous bleedings in these individuals, and which may very reasonably be interpreted as a sign of vascular engorgement; 2. the surprising toleration of excessive losses of blood ; and 3. the equally remarkable complete and rapid restitution of the volume of blood. Indeed, if we examine the second and third points somewhat more closely, we find that in many cases of haemophilia we have to deal not merely with a relative plethora (plethora ad vasa), but probably even with an absolute plethora, which enables these individuals to bear their apparently exces- sive losses so comparatively well just because it is itself the expression of an unitsually active power of generating blood. Our course of thought thus far has imperceptibly led us, as the reader sees, away from the consideration of the vascular anomalies and their effects upon the circulation, to the discussion of a second factor, which may possibly be of the highest impor- tance in the production of the bleedings of haemophilia—a factor, moreover, which is not dependent upon the configuration of the NATURE AND PATHOGENESIS. 71 vessels, but is ultimately connected with the absolute quantity of the habitual supply of blood. The greater this habitual supply and the more the vascular apparatus is permanently overfilled in consequence of it, the more readily the clinical symptoms peculiar to the bleeder diseetse may arise, and the greater will be the tendency, not merely to hemorrhages in general, but particu- larly to those of a prof use and difficultly controllable character. This being the case, it may readily be conceived that in certain instances the habitual existence of a high degree of absolute plethora may of itself be sufficient to maintain a bleeder disposi- tion without the intervention of the vascular anomalies above described. Or, in other words, we may suppose that although in moderate degrees of habitual plethora haemophilia requires for its development the concurrence of other favoring conditions on the part of the vessels (particularly delicacy of their walls, narrowness of the lumina), still the affection may now and then manifest itself as a clinical form of disease entirely unconnected with the vascular lesions referred to. Such an hypothesis would not only afford a sort of explana- tion for that minority of cases in which nothing abnormal could be detected in the position and structure of the vessels, but would also serve to account for many of the characteristic fea- tures of the more frequent cases in which the vascular anomalies were actually present. Evidently the introduction of this second factor—variations in the volume of blood—would be only a gain to the vascular theory of haemophilia, by bringing it into more complete accord with the facts, and by enabling us, without detracting from the essentially permanent character of the disease, to dispense with the conception of haemophilia as an anomaly incapable of fluctuation. Such a conception, however, is a logical necessity so long as we regard the haemophilia in these cases as depending solely upon the vascular hypoplasia, whereas in reality experience shows that the disposition of bleeders to hemorrhages, and the severity of the bleedings, are usually by no means the same at all times of life, but present all sorts of fluctuations which manifestly point to a varying intensity of certain causal factors. A vascular theory, moreover, which regards merely the position and structure of the vessels, without 72 IMMERMANN.—HAEMOPHILIA. taking into account also the fluid contents of the latter, would wholly fail to explain why in many cases the first visible out- break of the bleeder diathesis, instead of occurring as usual in early childhood, is postponed to a somewhat later period of life ; or why, on the other hand, the affection still more frequently declines in intensity with the advance of a-e, and, indeed, ulti- mately disappears entirely. But all these fluctuations and differ- ences in respect to the beginning, course, and termination of the disease at once become more intelligible the moment we recognize in the varying quantity of blood in bleeders a possible, if not a probable cause of variations in the disposition to hemorrhages. Furthermore, just as there ma}' be clinical cases of haemophilia in which the hemorrhagic diathesis is induced and maintained simply by an unusually high degree of habitual absolute plethora toithout any abnormity on the part of the vessels (see above), so also, on the other hand, it is to be noted particularly that even when these veiscalar anomalies are present, the symptoms of hcemophilia need not be invariably manifested. Thus, these symptoms will presumably be absent, if along with the dimin- ished capacity and imperfect development of the vascular appa- ratus there is also a corresponding diminution in the habitual volume of the blood, so that there is no habitual plethora ad vasa, no excessive distension of the thinned and narrowed, but still elastic arteries, by the systolic blood-wave. r>o long as the harmony between the quantity of blood and the capacity of the vessels is not materially disturbed, the haemophilia, although it exists in the germ on the part of the vessels, will still remain latent, and may possibly continue so for the entire lifetime ; but, should conditions arise which determine a temporary or perma- nent increase in the mass of blood, then the congenitally estab- lished haemophilia awakens, and a transitory or persistent hemorrhagic diathesis develops, the intensity of which -will depend chiefly on the degree of disproportion which now exists between the calibre of the vessels and the volume of blood. We come now, finally, to the question whether, besides the two conditions mentioned, there may not be still other auxiliary factors concerned in the production of haemophilia bleedings. either on the part of the bodily organization or on the part of the NATURE AND PATHOGENESIS. 73 vital processes of bleeders i To this question, if it be understood as applying to all cases of the disease without exception, we are by no means prepared to reply either negatively or still less affirmatively. For certain cases, however, the existence of such further predisposing factors may be conceded. In the first place, we may regard in this light the habitually forcible contractions of the heart, of which we have ample evidence in the unusually hard pulse and apex-beat of many haemophilist individuals, and particularly in the cardiac hypertrophy occasionally found at their autopsies. That such a functional hyperkinesis, and espe- cially an actual hypertrophy of the heart, will favor the forma- tion of a congestive diathesis, and thereby predispose to pro- fuse hemorrhages, is too evident to require detailed proof; but, besides this, the conditions in question, as they are both repeat- edly observed in bleeders, afford additional support to the theory of the actual existence in these very patients of a condition of relative or even absolute habitual plethora during life. For ex- perience shows that permanent hyperkinesis and hypertrophy of the heart are developed the more readily, the greater the quan- tity of blood in comparison with the obstructions to its move- ment in the circulatory apparatus. Some writers, on the other hand, interpret the motor excitation of the heart so frequently met with in bleeders, and also the increased thickness of the cardiac walls, as results induced by the increased richness of the blood in red corpuscles (Assmann), by means of which the heart is constantly kept in a state of increased functional as well as nutritive activity. Which of these two explanations is the cor- rect one, or whether both factors act in combination, we shall not attempt to decide.—Some other writers, finally, have preferred to regard haemophilia as due to a deranged inuervettion of the vessels. According to this view it is maintained that the bleeder diathesis, as well as the tendency of bleeders to rheumatic affec- tions (see Complications), are in the main vaso-motor phenomena connected with an unusual disposition in certain individuals to a neurotic relaxation of the vessels, which manifests itself in frequent capillary hyperaemias, stases, spontaneous hemorrhages, and, when a wound has been received, in imperfect contraction of the vessels (Otto, Reinert, etc.). Undoubtedly this theory 74 IMMERMANN.—HAEMOPHILIA. also has its claims as explaining in part the origin and course of many haemophilia bleedings, since the circulation is evidently influenced to some extent by the innervation of the vessels, and therefore a tendency to active neurotic dilatations of the vessels must a prieai be regarded as contributing to the occurrence of hemorrhages of a bleeder character. Still, in view of the ana- tomical and clinical facts previously mentioned, which permit within certain limits a grossly mechanical view of the clinical problem, there can be no propriety whatever, it seems to us, in advancing a vaso-motor theory of haemophilia in so exclusive a form as has been advocated by many writers, i. e., as a general theory applicable to all cases of the disease. AVe cannot but regard it as a questionable practice, when writers, instead of directing their attention to the more immediate and more pal- pable causes of disease, forthwith betake themselves for an explanation to the domain of the "nervous," that " sphere of pure dynamics'' to which recourse should be had only when no interpretation of the clinical facts can be found elsewhere. Restated in a succinct form, our present knowledge of the nature of haemophilia is probably fairly represented in the follow- ing conclusions: Haemophiliei is, in general, a congenital and habitual form of the hemorrhagic diathesis, in which the frequently recurring and readily induced hemorrhages probably, in most cases, owe their extraordinary vehemence, obstinacy, and danger to an equally congenital and habitual disproportion between the volume of blood and the capacity of the vascular apparatus, resulting in an abnormal increase of the lateral pressure with- in the vessels. In many instances, moreover, functional ere- thism of the heart and hypertrophy of the cardiac musculatitre, by inducing a tendency to congestions, also aid to an impor- tant degree in producing the hemorrhages, and in giving them their abnormal clinical character. Finally, neurotic influences may perhaps occasionally act as an additional factor by tem- porarily increasing the permanent congestive diathesis. Of the three factors mentioned in the above definition, we regard the first—the congenital disproportion between the volume of blood and the calibre of the vessels, or, at least the existence NATURE AND PATHOGENESIS. 75 of a congenital foundation for such a disproportion—as by far the most important and most essential pathological element of haemophilia. While, moreover, this disposition may obviously be brought about in various ways (sometimes solely by a hyper- plasia of the blood, sometimes solely by a hypoplasia of the vessels, and sometimes by both anomalies combined), and while, therefore, there is in etll probability no absolutely single patho- genesis for all cases of haemophilia, we are still of the opinion that at least most of the cases have a similar, and, indeed, com- plex mode of origin, as is shown by the fact that in most cases there are anatomical and clinical indications of the existence of both a vascular hypoplasia and an actual, not merely a relative, plethora. Upon this view, therefore, the majority of cases of haemophilia would probably arise in this wise, that in con- sequence of either hereditary or merely accidental influences operating in the original development of the body, the plastic force inherent in a certain tissue system (the vessels) is abnor- mally feeble, so that the evolution of the vascular apparatus, par- ticularly the arteries, takes place incompletely ; while at the same time the blood, which is so closely related histogenetically to the vascular apparatus,1 takes no part in this defect of nutri- tion, but, on the contrary, grows in a normal—in fact, an excessive manner, and this tendency, moreover, is maintained throughout life. Still, it must be admitted that a priori a parallelism in the growth of the vessels and blood is much rather to be expected than this contrast, which in our opinion constitutes the patholo- gical substratum of most cases of haemophilia ; indeed, this very presumption serves to explain why haemophilia is upon the whole so rare an anomaly, especially in comparison with the chlorosis of congenital origin. If, however, the growth of these two varieties of tissue during the embryonic development of the individual, instead of taking place harmoniously as usual, actu- ally proceeds disharmoniously so as to lead to the formation of the above mentioned complex defect in the original design, a further propagation of this vice by means of hereditary trans- mission in the future is, according to all analogy, not onby 1 See article on Chlorosis. Vol. XVI. p. 547. 70 IMMEEM ANN. —I I.-EMOPI IILI A. possible, but even highly probable, so that alter haemophilia has once arisen congenitally within a given family circle, the sub- sequent hereditary character of the disease follows naturally as simply a special application of the general law of heredity. Moreover, since the transmission of haemophilia takes place far more commonly in the cognatic direction, we might sup- pose in particular also that the maternal predominates over the male influence in the development of the vessels and blood ; nor is there anything at all unreasonable in this hypothesis in view of the known relations of the so-called parablastic tissue (His) to the maternal organism (ovule and follicle). Furthermore, in order to account for the remarkable fact that, although haemo- philia is almost always transmitted by the mother rather than by the father, the disease in reality manifests itself by a decided preference only in the male descendants (sons), we must be able to show either that the natural disposition to vascular hypoplasia or to plethora is stronger in the male sex, or that the female sex enjoys a relative immunity from one or the other anomaly of growth. Now, patho-anatomical experience teaches most posi- tively that hypoplasia of the vessels is by no means limited especially to the male sex, but occurs more frequently in females (see Chlorosis); on the other hand, the male organism, as is well known, is from the beginning distinguished from the female by a greater supply of blood, a more active haematopoiesis, and a more vigorous development of the cardiac muscle; and for these very reasons possesses, therefore, a much stronger disposition to absolute, as well as relative plethora, and at the same time, we may suppose, to haemophilia. It seems to us, therefore, in a high degree probable that when the hereditary hypoplasia is present in the male members of a bleeder family, and becomes, in connection with a plethoric condition of the blood-mass, the patho-anatomical substratum of a pronounced bleeder affection, the same hypoplasia may be supposed to exist also in the female members ; but that the latter do not themselves become bleeders simply because the bleeder diathesis is kept latent by certain normal attributes peculiar to the female organism, particularly by the smaller quantity of blood and the more feeble develop- ment of the cardiac musculature. In order to settle this point, NATURE AND PATHOGENESIS. / / however, it would obviously be necessary to ascertain definitely by careful post-mortem examinations whether the same hypo- plasia which is met with in the marked bleeders of a family is also present in the bodies of their non-bleeder mothers, sisters, and brothers. The decision of this question has never been seriously attempted, so far as we know, by any physician who has had the professional care of bleeder families, because hitherto the whole interest in regard to the morbid anatomy of the dis- ease has been confined to the actual bleeders without extending also to the non-bleeder (usually female) members of these fami- lies. Perhaps, however, the hypothesis which we have advanced may serve to direct the attention of the medical public to this subject, and it is solely with this view that we have treated it somewhat more fully than would otherwise befit the dogmatic tone required of a work of this kind. There is still another circumstance, moreover, which some- what modifies the effect of an hereditary and congenital vascular hypoplasia in the female organism, at least during the period of menstrual life, as compared with the male. Thus, the menstrued bleedings unquestionably act as a very effective derivative, thereby preventing over-filling of the vascular apparatus and the formation of a congestive diathesis. That the menstruation may, however, occasionally present a hemorrhagic type in females with narrow and thin-walled vessels, was especially insisted upon in our consideration of chlorosis ;1 indeed, we are free to confess that, to our mind, these rarer menorrhagic cases of chlorosis in women appear to be in reality quite a complete analogue of the haemophilia more commonly observed in males. We are, moreover, confirmed in this view by the fact that in male individuals the haemophilia has sometimes been observed to disappear after the establishment of periodic hemorrhoidal bleed- ings (see p. 60). In conclusion, we recur for a moment to another fact already alluded to several times, viz., that very commonly haemophilia, besides presenting various intermediary fluctuations in intensity, undergoes a gradual decline in its average severity with advein- 1 See Vol. XVI. p. 322. 78 IMMERMANN.—HAEMOPHILIA. cing age; and that sometimes, after the spontaneous bleedings have recurred with less and less frequency, and the traumatic hemorrhages have gradually lost their bleeder character, the diathesis disappears apparently spontaneously in the later years of life. In searching for the natural causes of this frequently observed peculiarity in the course of the bleeder anomaly, the most obvious explanation, it seems to us, lies in connection with that abatement in the physiological regenerative power in old persons, which manifests itself, as is well known, chiefly in the sphere of haematopoiesis, and gives rise, among other conditions, to a marked tendency to oligaemia (see Vol. XVI., p. 303). It is certainly easy to see that just in proportion as the formation of blood takes place less actively, any plethora ael vasa that may have existed will be relieved, together with the tendency to hae- mophilia bleedings, and that when this relief is incomplete, so that profuse hemorrhages still occur now and then, a much longer time will in general elapse after the attacks before the previous condition of plethora is reinstated. Hence, in old per- sons, as experience shows is actually the case, the spontaneous bleedings will probably occur only at longer intervals, and the traumatic hemorrhages will be of a less profuse character than in younger bleeders ; indeed, the blood-mass may finally become so reduced in the former that the bleeder diathesis is kept latent for the rest of life. The preceding views are intended to be regarded only as a provisional attempt to deduce from the empirical material ob- tained by autopsies and clinical observations a somewhat clearer conception of the nature and pathogenesis of haemophilia. To be sure, our exposition, as we freely admit, still leaves unex- plained many single points in the symptomatology and etiology of this remarkable affection, but we believe that justice has been done to at least some of the most important features of the dis- ease in both these respects, so far as seemed possible to us at present without resorting to gratuitous assumptions. Diagnosis. It is often extremely desirable, especially with reference to a DIAGNOSIS. 79 prophylaxis of the bleedings, to be able to diagnosticate the existence of a congenital hemorrhagic diathesis before the unwel- come fact is forced upon our attention by the occurrence of a dangerous hemorrhage. Such a providential diagnosis, as we may term it, is, however, possible only in hereditary cases of the disease, or in those of multiple congenital origin, but not in the primary and isolated cases ; because, although the manner in which the transmission and multiplication of haemophilia usually occur is now fairly well understood, we are still ignorant as to the mode of its primordial genesis. It is evident, therefore, that in some cases, notwithstanding the most careful examination of the patient's history and family record, a diagnosis will be impossible until after the occurrence of repeated hemorrhages, while in other instances a failure to foresee the eventual outbreak should be regarded as almost a crime. Far the most open to the suspicion of haemophilia are, in the first place, all individuals ivhose mothers belong to bleeder families, whether these mothers are themselves bleeders—as is comparatively rarely the case—or, on the contrary, are entirely free from the disease (see p. 26). Still more certain becomes the provisional diagnosis, if other children in the family have already been subjects of the affection ; and when this is the case, we shall at least err on the safe side if we continue to regard every male child born in such a family as a bleeder until future tests (acci- dental wounds, etc.) demonstrate the absence of a hemorrhagic diathesis (quisquis illorum habeatur haeme>philus, donee proba- verit contrarium /). Indeed, when haemophilia has once made its appearance in a family of children, the introduction of every new member, if a male, is always to be regarded with apprehension, even though no evidence of the disease is discoverable in the mother or her ancestry, for experience has shown that under such circumstances, where the disease has arisen de novo and has not been transmitted hereditarily, it far more commonly manifests itself in several children one after another than in a single one alone. On the other hand, haemophilia in the father is a far more uncertain guide in the presumptive diagnosis of the disease in the child; while, if the father merely belong to a bleeder family without being himself a bleeder, the indication is 80 IMMERMANN.—HAEMOPHILIA. of very subordinate value. In fact, all experience shows that under the latter circumstances the chances are altogether in favor of the child's not being a bleeder. In the presumptive diagnosis of haemophilia, therefore, the cog iodic relationships of the individual afford indications of far more importance than the agnatic. Still, as has already been mentioned in the Etiology, the general rule that the male offspring of mothers belonging to bleeder families are subjects of pronounced haemophilia, is by no means without exception ; indeed, many of these children, for reasons not well understood, remain entirely free from the affec- tion throughout life, or at least the diathesis maintains a com- plete latency in them. The diagnosis, therefore, in male chil- dren related as above described, can never be more than con- jectural, and can be fully determined only by the future course of the case. The absence of hemorrhages during the first few weeks of life, it should be remembered, is no indication of safe- ty, for the disease frequently delays its appearance until the end of the first, or even into the second year. Should, how- ever, the second year pass without the occurrence of haemo- philia bleedings, the chances will have diminished considerably, since, of the cases thus far carefully recorded, nearly 70 per cent, clearly manifested their nature before the expiration of this period (see p. 29). Still, even now the child is not entirely secure from a tardy outbreak of haemophilia until the full growth of the body has been attained ; from this time onward the immunity is complete, since there is not et single case on record of the outbreak of pronounced haemophilia for the first time after the twenty-second year of life. This rule, however, applies only to the fully developed bleeder disease ; the rudi- mentary forms may sometimes manifest themselves transitorily, for the first time, at even a later period. Far different, on the other hand, is it with the presumptive diagnosis of haemophilia in the female members of a bleeder family. In this sex the pronounced disease is so rare that its existence in a female, hitherto free from any of the symptoms, can in general be predicated only as a remote possibility, even though she belong to a bleeder family, and some of her nearest DIAGNOSIS. 81 male relatives (brothers, sons) be actual bleeders. Still, if the family have hitherto exhibited a marked tendency to the pro- duction of female bleeders ; if, for instance, the mother and sis- ters be notorious bleeders, the possibility referred to becomes somewhat more definite, and in exceptional cases may even attain to a degree of probability. Even under these special con- ditions, however, our suspicions will frequently prove erroneous. In marked contrast with the presumptive diagnosis of latent haemophilia, that is, of the bleeder disposition, stands the diag- nosis of the manifest disease. This, in pronounced cases, is usually unattended by the slightest difficulty, since the fre- quently recurring spontaneous bleedings, the extraordinary dan- gerousness of all traumatic hemorrhages from even the slightest causes, and the family history of the individual, together form an etiologico-clinical picture which is scarcely paralleled in dis- tinctness by that of any other anomaly. As for confounding such fully developed cases of haemophilia with other hemor- rhagic affections, especially scurvy and morbus maculosus Werlhofii, the danger is comparatively slight, because these cases are most completely marked by that hereditary or con- genital and habitual character which sharply distinguishes haemophilia at once from all other varieties of the hemorrhagic diathesis. Nor is there any greater difficulty in recognizing well marked haemophilia in the female sex than in the male ; for when a female individual has once clearly manifested a congeni- tal and habitual tendency to profuse and dangerous hemorrhages, there certainly need be no hesitation in characferizing the patho- logical condition as haemophilia; least of all, if the patient belong to a family of bleeders. Difficulties present themselves in the diagnosis of the manifest disease in the two sexes, as a rule, only when, 1. The case in ques- tion is the first of the kind in the family circle, and the hemor- rhage is the first in the history of the patient; or, 2. When we have to deal with a rudimentary case, or with one running an einomalous course. In the first place, as regards the correct recognition of & primary case of haemophilia, this is in general impossible during the first attack of hemorrhage, and we shall have to suspend our decision until repetitions of the bleedings VOL. XVII— G 82 IMMERMANN.—HAEMOPHILIA. have determined the habitual character of the existing hemor- rhagic diathesis. Still, in cases of this kind, haemophilia may at least be strongly suspected if the individual present no other indications of disease, and be a male child in the first or second year of life. On the other hand, the presumption is against the existence of haemophilia, when the primary manifestation of a hemorrhagic diathesis occurs in an adult without a hereditary history of the disease, and especially if the patient be a female. Finally, in rudimentary forms of haemophilia, especially in those which present merely the clinical character of a transitory hemorrhagic diathesis, it will rarely be possible to recognize the affection as an imperfect development of a congenital bleeder disposition, except when the case occurs within the limits of a bleeder family, and when other members of the same family circle present the disease in an unmistakable form (see p. 23). Cases of transitory hemorrhagic diathesis, in which we have no such indications to guide us, will usually have to be excluded from the category of haemophilia, and referred to some other dyscrasic affection of known nature, such as scurvy or morbus maculosus (see the two following articles). Duration—Terminations—Prognosis. The duration of haemophilia as a congenital hemorrhagic disposition probably always corresponds, on the whole, with the lifetime of the individual, since even in those cases in which the affection fails to "appear until after the first year, or gradually ceases with advancing age to manifest symptoms, the diathesis probably still exists in a latent form during the periods of apparent absence. When, however, the outbreak of the haemo- philia takes place at the very earliest period of life, and, as is unfortunately too commonly the case, the death of the individual results sooner or later from an attack of hemorrhage, then the congruence between the duration of the disease and the duration of life is clearly perceptible, and the habitual character of the affection stands out with special distinctness. The above remarks as to the duration of the pronounced forms of haemophilia will naturally apply also to those rudimen- DURATION AND TERMINATIONS. 83 tary cases which are observed especially in the female members, but occasionally also in some of the males of bleeder fami- lies, since in these cases also the bleeder disposition must be regarded as congenital. As regards their clinical duration, that is, the period during which the haemophilia bleedings manifest themselves, the rudimentary cases, as has been repeatedly pointed out, present a double type, since in many of them slight attacks of hemorrhage recur more or less frequently throughout life and therefore habitually, while in others the disposition remains entirely latent, with the exception of a single outbreak of greater or less intensity. The temporal course, therefore, of this latter type may present all possible varieties in the individ- ual cases, and is in general bounded by no definite limits. As regards, finally, the duration of the hemorrheigic attacks themselves, great differences are noticed also in this respect. In a case observed by Escherich, in Wiirzburg, the patient, a bleeder, bled to death in forty-four hours, from a slight cut received in a students' duel ; in another case, recorded by Wachsmuth, a young lady bleeder died during the wedding night, therefore within a few hours, from the effects of the defloration (rupture of the hymen); while in other cases hemorrhages have lasted several weeks before their termination in death, or their arrest just in time to save the life of the patient. That the attacks of syncope which take place towards the termination of excessive hemor- rhages are not always the forerunner of death, but are rather in some instances the very means of saving life, has already been pointed out in our description of the symptomatology of the dis- ease. The ultimate result of haemophilia in the great majority of cases is death, possibly in the very first attack, but usually from one of the hemorrhages in later life. The mortality of the disease is therefore very high, and at the same time also very premature, on account of the generally very early outbreak of the diathesis, and its intensity during the first period of life. A very large number of bleeders succumb to the murderous affec- tion in early youth, the rate of mortality between the first and seventh years being particularly excessive ; while only a com- paratively small proportion of bleeders suffering from the well- 84 IMMERMANN.—HAEMOPHILIA. marked and fully developed form of the disease escape the constantly threatening danger of a fatal hemorrhage, and at last reach the age when the diathesis is frequently observed to abate spontaneously or to become latent. There can be no question, therefore, as to the extremely pernicious character of haemo- philia, especially in childhood and youth. Although the age is not definitely stated in all the hitherto observed fatal cases of hemophilia, it is expressly mentioned in a very large number of the reports that the death occurred in " early childhood." Grandidier has compiled 212 cases in which the age at death was accurately known, and this table, which includes 197 males and only 13 females, shows clearly the excessive mortality of bleeder children between the first and seventh years of life: Within the first year. From 1 to 7 years. . . " 8 to 14 " 15 to 21 " 22 to 28 " 29 to 33 " 36 to 45 Over 50 ales. Females. Total 22 7 29 89 3 92 39 1 40 24 3 27 Total.................... 197 15 212 According to the above table, therefore, more than half of the entire number, 121 (111 males and 10 females), died from the affection before reaching the eighth year, and only 24 survived the twenty-second year. Instances are by no means wanting, however, in which bleeders have attained advanced age, even though the tendency to hemorrhages has continued undiminished. Thus, the head of the bleeder family Appleton-Brown died in old age (year of life not stated), of hematuria and bleedings from bed-sores (Hay); while Grandidier in his latest articles mentions patients—some of them perhaps still alive—who had passed their fiftieth, or even sixtieth year without having lost the tendency to hemorrhages. On looking over the causes which have induced the fatal hemorrhage in individual cases, one cannot but be struck with the high mortality from trifling wounds. Thus, the record shows that the extraction of teeth, circumcision, and the application of leeches are specially dangerous; less hazardous, but still attended with danger, are the minor operations, such as venesec- tion and cupping, while vaccination seems to involve but little PROGNOSIS. 85 risk. Among the accidental wounds, those of the face (especially the lips) appear to be most apt to excite fatal bleeding. The total number of known deaths thus far from extraction of teeth is thirteen, from ritual circumcision in Jewish children eight, and from the application of leeches five. Extremely dangerous, but not fatal hemorrhages after extraction of teeth, have been observed in more than forty cases. For further details, we are obliged by lack of space to refer the reader to the articles of Grandidier mentioned in the Bibliography. In many cases of pronounced haemophilia death results, even during the continuance of the disease, from other intercurrent morbid processes ; still these instances bear but a small propor- tion to those in which the fatal result is due to fatal hemorrhage. Finally, as we have already pointed out repeatedly, the hemor- rhagic tendency not infrequently decreases with the advance of age, or even becomes completely extinct, and therefore may be said to undergo an amelioration, or even a cure, in the clinical sense of the word. These favorable terminations of haemophilia, to be sure, usually occur only after the individual has suffered from the marked affection during his entire childhood and maturer life, and therefore only in the period of plrysiological decadence; still, isolated cases are recorded in which the ten- dency to hemorrhages has ceased in youth, or even in childhood (Thore, Lemp, Heath, etc.). After the subsidence and disap- pearance of the bleedings, the health of the patient is, however, by no means always perfect; usually, either during the period of remission or after the disposition has become completely latent, the previously mentioned complications and sequelae make their appearance, and delay or even absolutely prevent the full resto- ration of the patient's strength. Still, viewing the terminations of haemophilia as a whole, an early death appears to be so much more frequent than the other observed results, that the fully developed affection must unhesitatingly be pronounced one of the most dangerous anomalies in the entire range of pathology. The rudimentary cases of haemophilia are, of course, compara- tively less dangerous; still, a fatal result is by no means unknown even in them. Thus, it occasionally happens that a hemorrhagic disposition, which has hitherto developed imperfectly, or has 86 IMMERMANN.—HAEMOPHILIA. even been completely latent, suddenly surprises one by its out- burst in a profuse hemorrhage, which places the patient in immi- nent danger, or even actually destroys life (Zaar, Beyer, Otto, and others). After what has been said, but little need be added in refer- ence to the general prognosis of haemophilia. When the affec- tion has once clearly manifested itself with some degree of intensity in a child soon after birth or somewhat later in life, the prognosis must be regarded as, upon the whole, unfavorable, the chances being greatly in favor of a premature death ; while in the improbable case of a prolongation of life we must always take into account the extremely obstinate character of the anom- aly. Should the child, however, survive the eighth year, some hope may now be entertained that the organism, by virtue of its increased power of resistance, will be able to withstand the future bleedings ; still the danger is by no means passed, for any one of the bleedings in later years may prove fatal. On the other hand, the prospect will naturally be much more favorable if a tendency to latency be indicated by the diminished severity of the bleedings, and especially if an actual latency be demon- strated by the fact that slight accidental wounds run their ordi- narily favorable course. In the absence, however, of such satisfactory proof, one should be cautious about giving a more favorable opinion, because, even though the spontaneous bleed- ings have entirely ceased, the apparent recovery of the patient may at any moment be converted into a condition of extreme danger by some trifling accidental wound. Finally, if the affec- tion even in advanced age shows no tendency to spontaneous involution, the general prognosis will continue to be very du- bious so long as the disposition to profuse hemorrhages remains undiminished, and the latter occur from time to time with their former intensity. When, on the other hand, we have to deal merely with a rudimentary form of haemophilia, in which the disposition to hemorrhages is indeed permanent, but is only slightly marked, the general prognosis will naturally depend upon the average degree of intensity of the affection, and will therefore be, upon the whole, favorable quoad vitam. In such cases, moreover, a PROGNOSIS. 87 complete retrogression of the diathesis in after-life, and there- fore an actual recovery, can be calculated upon with much more certainty. In those anomalous cases, finally, in which the mor- bid disposition manifests itself only transitorily, the general prognosis coincides with the special prognosis, i. e., with the prognosis of the individual bleedings, to which we now pass briefly in conclusion. The special prognosis of haemophilia bleedings is modified chiefly by the nature of the existing hemorrhage. External bleedings are, as a rule, more serious that the interstitial forms, and among the latter the subcutaneous haematomata involve much greater danger than the cutaneous hemorrhages (petechia?, ecchymoses, vibices). • Next in importance comes the situation of the bleeding, since certain localities (the dental alveoli, lips, prepuce, etc.) are distinguished by specially profuse external hemorrhages. The locality is also of importance, in so far as it permits or interferes with the local application of styptics ; hence, internal bleedings are, ceteris paribus, naturally more dangerous than the external. In the third place, when repeated attacks occur, the prognosis in any given hemorrhage will be largely modified by the severity of the previous attacks, and therefore by the degree of the existing diathesis. If the previous attacks have been extremely profuse and threatening, every suc- ceeding hemorrhage will necessarily be regarded with increased apprehension. Still, if these large losses of blood have been well borne, so that the patient is known to have manifested a marked tolerance of diminutions in the volume of blood, this fact will, of course, enter as an important element into the present prog- nosis. The age and constitution of the patient are also impor- tant elements in cases of profuse and obstinate hemorrhage, because individuals of a very tender or very advanced age, or of a feeble constitution, will obviously be less able to withstand the exhaustion of such attacks. Finally, it should not be forgotten that the result in these hemorrhages, just as in other serious morbid processes, is often determined, not so much by the grav- ity of the local changes and the individuality of the patient, as by various external and purely accidental conditions ; and these the physician, in forming his opinion as to the probable result, 88 IMMERMANN.—HAEMOPHILIA. should weigh with scarcely less care than he devotes to the more general conditions mentioned above. Treatment. Although haemophilia is far from being a frequent affection, its great malignity, which has been the more clearly ascertained by reason of this very fact, renders the inquiry after a radical prophylaxis entirely superfluous. So far, however, as a prophylaxis is possible, the end in view is two-fold: 1. To prevent the occurrence of new cases of the disease ; and, 2. Where the bleeder disposition already exists, to check its manifestations (the haemophilia bleedings). We may therefore speak of a general and of a special prophylaxis of haemophilia. As regards the general prophylaxis, the main fact to be dealt with is the marked transmissibility of the disease, since in by far the majority of cases pronounced haemophilia is not of indepen- dent congenital origin, but is rather the result of direct, especially indirect, hereditary transmission (see Etiology). It is clear, therefore, that much might be accomplished in the way of check- ing, though not of entirely suppressing the further propagation of the disease, if, in spite of declamatory appeals for " the liberty of the subject1' on the part of doctrinaire enthusiasts, all mar- riages likely to result in the procreation of new generations of bleeders were legally prohibited. In the absence of such a governmental restriction the physician is unquestionably war- ranted in using his personal influence to prevent such marriages, by pointing out to the individuals concerned the seriousness of the danger, and by appealing to their consciences to desist from a step which might involve disaster to their posterity. For, however little right the physician may have under ordinary cir- cumstances to interfere in the private affairs of his patients, the evil to be avoided is here so great that energetic efforts to avert it are certainly in every respect justifiable. The same warning is equally necessary also in the case of healthy individuals, who, ignorantly or thoughtlessly, are on the point of connecting themselves by marriage with a bleeder family. Still, there is TREATMENT. 89 clearly no warrant for such interference with the personal rights of individuals, whether by the government or by the physician in his private capacity, except when the danger is commensurate with the sacrifice required. To enforce celibacy, as W. Legg has recently advised, upon all members of bleeder families—males and females, bleeders and non-bleeders alike—merely because the disease may possibly appear in their offspring, seems to us to be carrying caution to excess ; the most that we can reason- ably demand is a restriction of this kind when there is a prob- ability of the disease being transmitted. Now, as we have already seen, experience has shown that the capacity for trans- mission does not exist in all the members of the families, but only in certain categories of the same, and that in the other mem- bers the danger is so slight as not to require a prohibition of marriage. In this latter class may probably be included all male members of a bleeder family who are not themselves bleeders, since the transmission of haemophilia by such individuals is among the rarest of clinical events. On the other hand, mar- riage should^ be forbidden to all the females of a bleeder family loithout exception, because the female sex possesses in an eminent degree the power of transmitting disease, especially haemophilia, and this capacity exists in the non-bleeder as well as in the bleeder females of such families. In the case of a male bleeder, it is to be borne in mind that the children begotten by marriage with a healthy woman are, to be sure, frequently, but by no means uniformly, subjects of haemophilia, and that while the danger of hereditary transmission is, therefore, greater than in the case of the non-bleeder males of such families, it is far less than that attending the marriage of the female members, either bleeders or non-bleeders. Still, generalizations of this kind are of little assistance when we are called upon to determine the risk in individual cases, and it will be far better, therefore, to be guided by the special history of the family as regards the mode in which the disease has hitherto been transmitted. Thus, if the record shows that repeated instances have occurred in which haemophilia has been handed down in an agnatic direction (from father to son), the marriage would be morally unjustifiable ; while, if the tendency to hereditary transmission has been noted only in the 90 IMMERMANN. —HAEMOPHILIA. female members, no reasonable objection can be urged against the marriage of a male member, even if he were a marked bleeder. In this connection we may refer again to the two large bleeder families at Tenna, in Graubiinden, in which families, according to Viele, the disease has always been propagated by the females and never by males, although the latter have all been marked bleeders, and many of them had numerous offspring by marriages with healthy women. Indeed, experience seems to have taught this community the natural solution of the question at issue, for we find that the marriage of the males in these families has come to be regarded as entirely unobjectionable, whereas in 1S55 the few female members still living had all abstained from marriage. If the disease at Tenna do not desert the mode of transmission it has hitherto followed, there is good reason to expect its complete extinction in a not very distant future. "Wo have not been able, however, at the present date (1875), to ascertain the number of bleeders still living in this part of Rhaetia, and are consequently not prepared to say how far this highly desirable result has as yet been actually attained. In the preceding suggestions as to the general prophylaxis of haemophilia are comprised the principles which, it seems to us, should guide the physician when he is consulted, or feels himself compelled to volunteer advice, in regard to a contemplated mar- riage where one of the parties belongs to a bleeder family. As we have seen, there are in these alliances favorable and unfavorable conjunctions, and the physician, who knows how to read aright the different constellations which are possible in such cases, will often be able to allay unnecessary anxiety or to avert an impend- ing evil. The state of affairs is, however, of course materially changed when the marriage has already been consummated ; the aspects must now be regarded as unfavorable, and the danger urgent that a progeny will result composed partly of actual bleeders and partly of conductors of the disease. The best that can be hoped for from such a marriage is that "nothing will come of it'' —that it will remain unfruitful. The physician should, therefore, regard it as his duty, when opportunity presents, to emphatically express this ungracious wish to the married couple ; but here his obligation naturally ends, and the task of prophylaxis must now be left to a private under- standing between the individuals themselves. The same remark will apply also to those cases in which a healthy married couple, neither of whom belongs to a bleeder TREATMENT. 91 family, have, from unknown causes, begotten a bleeder child. Here, where the disease has not been transmitted hereditarily, but has evidently arisen congenitally, there is still reason to fear that the same prejudicial influences which have co-operated in the procreation and development of the first bleeder child, will continue to act in the future, since experience shows that in such cases the haemophilia does not remain isolated, but reappears successively in several children. In this case also the danger of further progeny should be explained to the parents, and the future responsibily shifted to their own intelligent action in the matter. Again, it may happen that a marriage which has resulted in the procreation of bleeder children may be dissolved by the death of one of the parties, and the question may then arise whether the survivor should be allowed to remarry. In decid- ing this question it will be necessary to ascertain definitely whether the affection in the children is of hereditary or of con- genital origin. In the former case remarriage may be permitted, whatever the mode of transmission, whether through the mother or father, provided it can be shown that the deceased is the one through whom the conduction has taken place. For all experi- ence hitherto has shown that in such remarriages no instance has occurred in which a man previously married to a woman of a bleeder family has begotten bleeder children by a second mar- riage with a healthy woman, or in which a healthy woman pre- viously married to a male bleeder has contracted the latent disposition by such relation so as to beget bleeder children by a subsequent marriage with a healthy man. On the other hand, examples are not wanting in which the misfortune of begetting bleeder children, once begun by a wife from a bleeder family in her first marriage, has been continued in a second series of chil- dren by a subsequent husband (Grandidier, Keinert). Of course such a remarriage should not be allowed to take place without energetic protest. When, however, the haemophilia in the children is clearly not hereditary, but is of independent origin, it is naturally much more difficult to determine the relative degree of responsibility on the part of the two parents for its occurrence, and the question 92 IMMERMANN.—HAEMOPHILIA. of remarriage by the survivor is, therefore, to a certain extent an open one. Still, if we bear in mind the fact upon which we have already laid such repeated stress, that the capacity for transmitting haemophilia inheres, in a far higher degree, in the female sex, the remarriage of the mother in such cases will appear much more objectionable than that of the father; and it will be seen to be altogether probable that, even when the disease origi- nedes independently, it is mainly dite to the influence of the mother. What the real nature of these primordial influences may be through which haemophilia is begotten in the foetus we shall not attempt to decide; but we are satisfied that when bleeder children have appeared in a family, it is clearly advis- able for the mother to abstain from remarriage, even though no cases of the disease had occurred on either side of her family previous to its appearance in her offspring. The preceding remarks must suffice here to point out the way in which the state or the private physician may interfere to check the further propagation of haemophilia, without un- necessarily sacrificing the rights of the individual; and if the directions given were strictly carried out, there is little doubt that in the course of time the affection would become considerably less frequent than it is at present. A complete eradication of haemophilia, however, by such "means, is impracticable, and, in fact, impossible by any method known at present. For until we have discovered those obscure primordial causes which every now and then determine the occurrence of primary cases of haemophilia—after which the farther propagation of the disease takes place in accordance with definite known rules —we shall never succeed in cutting awray the deeper roots of the disease, and in thus eradicating it at the very start. The investigation of the primordial causes of the disease remains, therefore, now as in the past, the necessary preliminary to a radical prophylaxis ; and the preventive measures suggested above, notwithstanding their great practical importance, will consequently always possess only a secondary value in the eradication of the disease. In passing now from the general prophylaxis of haemophilia —the prevention of new cases of the disease—to its special TREATMENT. 93 prophylaxis, we come to a task of scarcely less importance, viz., the prevention of the haemophilia bleedings. When the suspicion of such a diathesis rests upon a new-born child, all influences likely to excite these bleedings should, of course, be carefully avoided from its very birth, and especially after the existence of the affection has been demonstrated by one or more dangerous hemorrhages ; nor should these precautions be withdrawn, either in the merely suspected or in the pro- nounced disease, until sufficient evidence has been accumulated by the results of accidental wounds, that involution has taken place, or that the original suspicion was incorrect. The special prophylaxis of haemophilia, therefore, not only begins, when possible, with the birth of the individual, but in very many cases must continue even throughout life. This vigilance, moreover, although of course necessary against traumata of all kinds, is to be directed especially against those likely to excite a superficial hemorrhage, because this form of bleeding has been found to be far the more dangerous to bleeders. Trifling injuries, particularly, should be sedulously avoided, because these are most apt to occur accidentally, and therefore require greater circumspection for their prevention. As regards the intentional infliction of wounds—even the most insignificant operations attended by loss of blood—the same precaution is equally necessary ; even when indicated, they should not be per- formed if any other operation not involving hemorrhage can be substituted, or if the patient's condition does not demand the operation imperatively. When, however, surgical interference cannot be postponed, on account of the vital indications, the operator should prepare himself with all the means, to be pres- ently described, for arresting the hemorrhage as speedily as possible. To these general rules we may append a few special indica- cations in reference to the prevention of wounds. First, as regards accidental injuries, care is evidently most necessary during the period from the birth of the child up to its eighth year, because the manifestations of the disease are most pro- nounced and the loss of blood most dangerous at this time, and because the patient is less competent to take the necessary pre- 94 IMMERMANN.— HAEMOPHILIA. cautions for himself. During school life, moreover, incessant watchfulness is still imperative, for now the child is exposed to danger from accidents in his boisterous play with his schoolfel- lows, as well as from his irrepressible desire for physical action of all kinds. If gymnastic exercises are a part of his school curriculum, however desirable they may be in other respects for his physical development, the family physician must see to it that the child is excused from engaging in them. Should this hard-fought battle of childhood be fortunately survived, there is still to be met the question as to his future avocation and his physical responsibility to the state and community. Of course, all the more directly mechanical employments, which involve any considerable danger of accidents, are unsuitable for bleed- ers ; and, when a choice is possible, the child should be educated for one of the "learned" professions, in which he will be better protected from the rough contact of the external world. As regards military service, we agree entirely with Grossheim (1. c), in his opinion that all bleeders should be unconditionally exempt, and the same remark, will apply also to similar duties, such as the fire service required in many communities. These indications will suffice, without going into further details, to show the manifold character of the measures necessary in the prophy- laxis of haemophilia, and the serious importance of the disease in its social aspects. As regards operations, little need be added to the general cau- tion already given. There are, however, two operations—the one a religious, and the other a social duty—which are of such impor- tance as to deserve consideration in some detail. We refer, of course, to the lewish rite of circumcision, and vaccination. With respect to the former, while we have nothing to object to it in general as an honorable custom sanctioned by ancient tra- dition in a religious community of the highest respectability, we still agree with Henschel, Finger, and others, that its observ- ance in Jewish bleeder families should be strictly prohibited in view of the unfortunate results that have attended the operation under these circumstances. The practice which has been adopted in certain Jewish families, of substituting baptism for circumcision, of course serves no moral purpose either foi TREATMENT. 93 Judaism or Christianity, and it seems desirable, therefore, that the rite should be modified in some way for Jewish bleeder chil- dren, so that they can fully satisfy the religious requirements of their faith without running the risk of hemorrhage. As regards the now almost universal practice of vaccination, it is fortunate that this minor operation is attended with much less risk than circumcision, otherwise the mortality among bleeder children would inevitably have been far greater than it is. Indeed, experience has abundantly shown that vaccination is one of the least dangerous operations in bleeders, and there seems to be no good reason, therefore, why bleeder children should be deprived of its benefit. Still, the profuse hemorrhages which have occasionally occurred during its performance teach the necessity of the physician's being prepared with proper means for immediately arresting any considerable bleeding that may arise. Among other minor operations, the object of which is simply curative rather than the fulfilment of a religious or social duty, may be mentioned, on account of their frequency, the extraction of teeth, venesection, and cupping. As regards the extraction of teeth, there are few points upon which writers are so unanimous as the extreme danger of this particular operation in bleeders. The patient, therefore, should be specially warned of this danger, and all the more because usually the family physi- cian is not consulted, but rather some dentist who is not aware of the nature of the case ; and because, moreover, the tempta- tion to have the operation performed is particularly frequent in bleeders on account of their predisposition to violent rheumatic toothache. Less dangerous is venesection ; still, this is never to be undertaken in a bleeder without urgent necessity—a condition which is not likely to occur frequently under the present indications for bloodletting. With respect to cupping, it is only necessary to remark that, while death has rarely resulted from its performance in bleeders, serious hemorrhages have not been uncommon. Indeed, all of these measures are contra-indicated, and should be replaced, when possible, by others which do not involve loss of blood. Furthermore, every precaution should be taken to avoid all 96 IMMERMANN.—HAEMOPHILIA. influences which determine the occurrence of plethora and con- gestions. Under this head may be included everything which occasions for the time being any considerable distension of the blood-vessels, violent action of the heart, or a strong determina- tion of the blood to the surface of the body: (1) the excessive use of fluids, particularly hot stimulating drinks (coffee, tea, alcoholic beverages) ; (2) over-indulgence at the table ; (3) consti- pation ; (4) severe bodily exercise, especially during warm, sultry weather, as well as at other times when the patient is laboring under vascular excitement ; (5) intense mental emotion. On the other hand, the diet, while it should be moderate in quantity and easily digestible, ought to be of a nourishing character. In place of tea and coffee, cold milk may be used ; and to quench thirst, water or lemonade in not too large quantities. Finally, the patient should lead a quiet, though not idle life, as free as possible from exhausting labor and mental excitement. We have now given what appear to us to be the most impor tant indications for the rational prophylaxis, both of the diathe- sis itself and of its manifestations—the haemophilia bleedings ; at the same time we have no hesitation in saying that at present more can be accomplished in the way of prevention than by attempts to eradicate the disease after it has once been estab- lished. At least none of the plans of treatment suggested thus far have stood the test of experience. To be sure, individual cases of partial or complete success, after the prolonged use of certain remedies, have been reported, but in other instances the same treatment has proved completely useless. AVhen the bleeder disposition, therefore, already exists, we are practically limited to measures for the prevention of the bleedings, or for their arrest during the attacks of hemorrhage. Among the various means by which it has been proposed to counteract the he- mophilia disposition, and thus to satisfy the indicatio morbi, may be mentioned, in the first place, the tonics and astringents employed with the view of strengthening the fragile capillaries. Thus, among the tonics, cod-liver oil has been advocated by Rieken, and iron by Heyfelder, Kopp, Martin, Vieli, and Legg. As regards the use of iron, Virchow has very properly pointed out the necessity of caution when there are evident indications of plethora or an excited action of the heart. These symptoms, however, are of such common occurrence in bleeders, either as habitual TREATMENT. 97 manifestations of the disease or as forerunners of the bleedings, that the use of iron for prophylactic purposes must, upon the whole, be regarded as contra-indicated. Its temporary employment during the acute anaemia following profuse hemorrhages is, of course, not open to this objection; in fact, the advocates of this remedy in haemophilia seem to have employed it especially at such times. Astringents have also been used in various forms: externally—tannin baths, ablutions with solutions of sulphate of iron, decoctions of sage, diluted vinegar, etc.; internally—prepara- tions of bark, rhatany, cascarilla, and, during periods of vascular excitement, large doses of acetate of lead, ergot, and ergotin. Formerly, with the view of allaying the vascular excitement more effectually by diminishing the force of the heart's action, even periodical bloodletting was resorted to ; but latterly, since this measure has been found to be so dangerous, digitalis in large doses, or navseants, such as tartar emetic and ipecac, have been preferred, and in some cases the treatment by such depressants seems to have been followed by a temporary amelioration of the tendency to congestions (Grandidier). It is clear, however, that such reme- dies as the acetate of lead, ergot, digitalis, and nauseants, cannot be used for any considerable period, and that they are therefore adapted not so much to an extir- pation of the diathesis as to a palliation of its manifestations at a time when they are seriously threatened. At such times, moreover, saline cathartics, especially Glauber's salt, have been used for the relief of the existing plethora. The latter salt was originally employed for this purpose as a domestic remedy in an American bleeder family, and is said not only to have exerted a favorable influence upon the course of the bleedings (vide infra), but also to have produced a permanent effect upon the diathesis itself. Still, this effect was by no means constant or lasting in all the cases; indeed, there is no reason to suppose that laxatives, any more than other drugs, can act in a directly curative manner upon the structural anomaly which underlies the disease. In passing now to the symptomatic therapeusis—the treat- ment of the bleedings themselves—we are met at the outset by the question whether, in cases of spontaneous external hemorrhage of non-traumatic origin, the treatment for its arrest should be at once undertaken, or whether the loss of blood under these circumstances should not rather be regarded as exercising a beneficial derivative influence. For, since these bleedings are commonly preceded by various symptoms of plethora and con- gestion, and therefore probably result from engorgement of the vessels, it is certainly possible that in checking the hemorrhage prematurely we might do far more harm than good. This view has been expressed by numerous writers, both formerly and in recent times (Consbruch, Thormann, Lowthorps, Tamme Beth, Wachsmuth, Vieli, Stromeyer, and Legg): indeed, some of these VOL. XVII.—7 98 IMMERMANN.—HAEMOPHILIA. authorities maintain that, after a rapid arrest of the bleeding in such cases, severe and dangerous symptoms are observed, in the form of extremely violent palpitation, oppression for breath—in fact, even apoplectic attacks and general convulsions. Other writers, however (Reinert, Assmann), have not been able to satisfy themselves' of any injurious results from the abortive treatment in spontaneous hemorrhages, and advise that energetic measures should be used at the very outset, just as in the trau- matic bleedings. The question, therefore, is still a mootable one, and can only be decided by the results of future experience; still, our own conviction is that early interference, in these cases is at times attended with danger. Such delay, however, should never be continued too long. Its only object is the relief of the existing plethora, and when in the judgment of the physician this has been secured, he should at once interpose without waiting until the hard, full pulse and flushed appearance of the patient have given place to an anaemic condition of the vascular system, general pallor, and exhaustion. It is certainly far better in such cases to err on the safe side, for there can be no doubt that under any circumstances an excess of blood is to be preferred to a deficiency, and that it is no part of the treatment to permit the patient to pass into a state of patho- logical anaemia. Another contra-indication against long delay is the difficulty with which every protracted hemorrhage is arrested, on account of the altered (hypinotic) condition of the blood which ultimately results under these circumstances. In the traumatic external hemorrhages, however, all authori- ties agree as to the necessity of immediate interference. Nor is there any difference of opinion as to the means by which the arrest of the hemorrhage is to be effected, the same remedies being equally suitable, whether the bleeding is of traumatic or non-traumatic origin, or whether the active treatment should be begun early or somewhat later in the attack. Of the means recommended for the arrest of these ■ bleedings, some are local, others general in their action ; a combination of both methods, however, will be found more effectual than a too exclusive reliance upon local styptics. Among the local measures, com- pression, continued for a considerable time, perhaps for days, is TREATMENT. 99 the most reliable, and, when the situation of the hemorrhage permits, should be first tried, either by means of manual pressure or by means of a tampon, graduated compresses, cork plates, etc. Sometimes, however, in the smaller wounds, cauterization by nitrate of silver, or, in the larger wounds, the application of ice, perchloride of iron, or a solution of tannin, will suffice to produce a momentary coagulation of the escaping blood; still, to produce a permanent effect, such styptics should always be followed by compression of the wound. In using pressure, however, the danger of producing gangrene—an accident that has occasionally happened under these circumstances—should always be borne in mind, and the compression should not be more forcible nor longer continued than can be employed with safety (Grandidier). In the treatment of very small wounds, such as leech-bites or simple linear incisions, the twisted suture has in many instances been found of great service and but rarely followed by secondary hemorrhages. On the other hand, the actual cautery, and other applications producing a temporary crust over the bleeding surface, rarely suffice to arrest the bleeding permanently ; they merely conceal the source of the hemorrhage for the time being, and only add to the difficulty of applying the compression which is generally afterwards required (Grandidier). Among the more frequent external bleedings, few present so much difficulty in their arrest as those which occur from the dental alveoli after the extraction of teeth. The most effectual treatment for this form of hemorrhage is the application of a tampon saturated with a solution of the perchloride of iron. The retention of the tampon may be effected either by a piece of cork—which is sufficient in some cases—or, still better, by the method recently suggested by Hohl,1 viz., to cover the plug with a gold or silver plate clasped to an adjacent tooth by platinum wire, so as to effect permanent pressure for several weeks, if necessary. This operation can be readily performed by any dentist. At the same time other measures should never be neglected, such as the application of ice-bags, derivative foot-baths, and internal treatment so long as the hemorrhage continues. Great caution is necessary also in 1 Deutsche Klinik. 1871. Nr. 42. 100 IMMERMANN.—HAEMOPHILIA. regard to the too early removal of the tampon and its cover- ings. As we have already mentioned incidentally, internal treat- ment is always advisable in these cases ; indeed, it has not unfrequently happened that this method has succeeded in rapidly arresting the hemorrhage after local measures have proved entirely fruitless. In cases of internal bleeding, where it is difficult or impossible to use local styptics, we are of course com- pelled to rely exclusively upon internal remedies ; but, even when the case permits the use of local treatment, the combined method by both general and local measures will be found to be more efficacious. Of internal remedies, the most trustworthy are acetate of lead and ergot in large doses frequently repeated (Schaefer, AVachsmuth, Meinel, Grandidier, et al.) ; the mineral acids, alum, tannin, and perchloride of iron, are less reliable for internal use. In every case, therefore, when the hemorrhage is at all serious, either acetate of lead in half-grain doses every two hours, or ergot in doses of 15 or 20 grains at the same inter- vals, should be given until the hemorrhage is arrested, or unmis- takable symptoms of poisoning are produced. As regards the use of Glauber's salt in large cathartic doses, to control the bleedings of haemophilia—a treatment recommended by Otto, who was struck with its success in the case of the bleeder family Smith- Shepard (see above), and was satisfied of its efficacy by trial in several of his own cases—the testimony in its favor is by no means uniform. Rieken and Elsaesser found it entirely useless ; Wachsmuth, however, praises it highly, and insists upon its use at the very start in traumatic hemorrhages, and as early as the second day in spontaneous bleedings. He gives it in laxative doses of from three drachms to an ounce repeated daily. That the good effects, when obtained, result from the derivative action induced by the catharsis, is shown by the similar experience with other laxatives, such as sulphate of magnesia (Fordyce), bitartrate of potass a, sennet, tamarinds, etc. Furthermore, the directions previously given for the preven- tion of vascular excitement when a spontaneous hemorrhage is threatened, are obviously still more necessary when the bleeding, whether spontaneous or traumatic, has actitally taken place. TREATMENT. 101 Thus, it is extremely desirable during the hemorrhage that abso- lute rest and freedom from excitement should be strictly main- tained. A low diet, and only a moderate allowance of cool drinks, with entire abstinence from alcoholic stimulants or hot liquids, such as tea or coffee, should also be enforced; and, when circumstances permit, the bed should be placed in a large, airy chamber. Of course it will not unfrequently happen, after these bleed- ings have continued for some time, that the sedative treatment above described will have to be replaced by the use of restora- tives. Thus, when symptoms arise which threaten a complete arrest of the heart's action, such as a sense of suffocation, attacks of faintness, or actual syncope, the temptation to resort to stimu- lants—wine (champagne), brandy, rum, camphor, ammonia—for the purpose of supporting the patient through this crisis, is almost irresistible. Still, necessary as this mode of treatment undoubtedly is'when the symptoms are extremely threatening, it is always to be borne in mind that syncope has sometimes proved to be the very means by which the hitherto uncontroll- able hemorrhage has been arrested, and that, therefore, a too early resort to strong stimulants is undesirable. At all events, it is safe to say that stimulants are contra-indicated so long as there is reason to apprehend an aggravation of the hemorrhage from any considerable increase in the force of the heart's action. The same objection will apply also to the premature employment of transfusion (Grandidier), to say nothing of the danger of a fresh hemorrhage from the wound inflicted in the operation. To be sure, a few cases have been reported in which life has been saved at the last extremity by this means (Lane)'; still, except in desperate cases, it is far better, in our opinion, to avoid the operation altogether than to undertake it prematurely. After the immediate danger from the hemorrhage itself has been passed, the profound exhaustion, which sometimes remains for days or weeks in the more serious attacks, is best combatted by efforts to simply maintain life, such as enforcing the recum- bent posture, and absolute rest of body etnd mind, rather than 1 The Lancet. 1840. p. 185. 102 IMMERMANN.—HAEMOPHILIA. by a direct resort to stimulants, restoratives, tonics, etc. For experience has amply shown that, when the expenditure of vital force is restricted as far as possible, life can often be maintained for a considerable period in man, just as in the lower orders of animals, upon very small supplies of food, air, etc., and that bleeders particularly possess a marked tenacity for life under these circumstances. In the administration of food, therefore, the quantity should at first be limited, and increased gradually as the appetite revives ; while as regards liquids, the burning thirst from which these patients suffer (see Vol. XVI., p. 347) should be allayed by often repeated, but small draughts of cold water or cold milk, to which, so long as the pulse and heart-beat remain alarmingly feeble, a few drops of brandy or rum may be added. When the indication has been fulfilled, it is better to discontinue the use of such "restoratives," and trust simply to a gradual revival of the patient's strength by means of long-con- tinued rest and a bland, easily digestible diet. By this simply hygienic and "unheroic" mode of treatment we shall at least most effectually guard against the premature occurrence of a new hemorrhage. For the same reason, caution is equally neces- sary in the use of all the more active tonics, and, therefore, the ferruginous preparations should be reserved for those cases in which the exhaustion and pallor continue for an unusually long- time after the arrest of the hemorrhage. A trip to the country, sea-bathing, and other roborant measures may also be prescribed in such cases. On the other hand, when, as so often happens, the patient rapidly loses his pallor, and, like Uhde's patient (see p. 44), becomes again within a comparatively short time "as blooming as a rose," the physician may obviously content him- self with enforcing the above restrictions as to rest and diet. The interstitial cittaneous hemorrhages (petechiae, ecchy- moses, vibices) require no special treatment in bleeders, since the loss of blood is inconsiderable even when the extravasation into the tissue of the skin has been of large extent, and since, moreover, we possess no means for hastening the gradual involution which these pitrpura-efHorescences undergo spton- taneoitsly. As regards the treatment of the subcutaneous interstitial hemorrhages—the haematomata—-it is of the first TREATMENT. 103 importance to protect these tumors from mechanical injury, and to abstain from opening them prematurely by incision or punc- ture. The affected limb or part of the body is to be kept as quiet as possible, and an effort made to effect a gradual disinte- gration of the tumor by means of cautious pressure, the appli- cation of lead-water bandages, moist warmth (Priessnitz's com- presses, poultices), etc. Opening should be resorted to only when the discolored appearance of the tumor makes it certain that gangrene has begun. In these cases, which are fortunately not frequent, caustics are preferable to the knife ; still, even when the former are used, profuse and dangerous hemorrhages almost always ensue, requiring for their control the energetic employ- ment of the various measures previously mentioned. Finally, the complicedions of haemophilia are to be treated in the same way as under other circumstances, with the important exception that all remedies should be carefully avoided which may possibly excite hemorrhage. Thus, in the rheumatic affec- tions, which are so frequently observed in bleeders, local blood- letting and severe counter-irritants, such as blisters, the local application of tincture of iodine, and similar measures for the relief of pain, are contra-indicated on account of their repeatedly observed tendency in these cases to produce excoriations which give rise to uncontrollable bleedings. As substitutes for these stronger applications, therefore, we should prefer the milder rubefacients (spts. camphorae, opodeldoc), or anodyne liniments containing hyoscyamus, chloroform, etc. ; while the absorption of the effusion may be promoted by moist warmth, or by alco- holized watery solutions of iodide of potassium. It is important, moreover, that the painful and inflamed parts should be pro- tected from mechanical injuries by soft coverings and supports. Furthermore, when the locality permits, bandaging the parts so as to secure absolute rest to the joints, muscles, etc., from both active and passive movements, will be found of great service just as in the ordinary forms of rheumatism. Lastly, some writers (Vieli, Grandidier) assert that in the treatment of these rheu- matic affections the use of mercurials in any form, and however prudently administered, is commonly attended by a temporary aggravettion of the hemorrhagic eliathesis, and therefore should 104 IMMERMANN.—HAEMOPHILIA. be strictly avoided. We simply record this opinion without attempting to explain the supposed idiosyncrasy ; but the warn- ing, if well founded, will undoubtedly apply also to the treat- ment of the other complications of haemophilia, particularly those of an inflammatory character. As regards these other complications, inasmuch as their usual course is not specially modified by their connection with haemophilia, Ave have nothing further to add in the way of treatment, except to reiterate the fundamental caution already repeatedly given, viz., to strictly avoid all remedies or applications which in their effects involve even possibly the risk of hemorrhage. '/ Scurvy, Scorbutus. (German: Scharbock}) J Literature. Euritius Cordus, Botanologicon. Colon. 1534. p. 94.—Agricola, Med. Herbar. Basil. 1539. p. 77.—Echtius, Da Scorbuto, vet Scorbut. passione epitome. Vitemberg, 1541.— Olaus Magnus, De gentium septemtrionalium conditionibus, etc. Rom. 1555. Libr. XVI. Cap. 51.—Ronsseus, De magnis Hippokiatis lieni- bus. Comment. Antwerp, 1564.—Joh. Wierus, Observ. rar. lib. I. de scorbuto. Basil. 1567.—The same Arzneibuch von etlichen besonderen Krankhciten, Scharbock, etc. Frankfurt, 1580.—Robert Dodonaeus, Medic, observat. exemp. rara. Col. 1581. Cap. XIII.—Severinus Eugalenus, De morb. scorbut. liber. Brunon. 1588.—Brunner, Tractat. duo. Rostock, 1589.—D. Randovius et St. a Schoenefeldt, Propos. sequent, de scorbuto. Diss. Rostock, 1589.—S. Albertus, Scorbuti historia, etc. Vitemb. 1594.—P. Forestus, Libri XX. de lienis morb. et de scorbuto novo morbo. Lugd. Batav. 1595.—F. van d. Mye, De rnorbis et symptomatibus popularibus. Bredanis, etc. Antwerp, 1627.—J. Roetenbeck et A. Horn, Specul. scorbuti. Nor. 1633. Consilium medicae facultatis Hafniensis de scorbuto. Hafn. 1661.—O. Charleton, De scorbuto liber singularis. Lond. 1651. —Paule Barbette, Praxis medic, et chirurg. Amstelodam. 1661.—Felix Plater, Praxis medicae. Lib. III. Cap. 4.—Thomas Willis, Tractatus de scorbuto. Oxoniae, 1667.—AV. Vernette, Traite du scorbut ou mal de ter et de tout. 1 Writers differ as to the etymology of this word, the source of which is probably the same as that of our English '' scurvy " and the Latinized " Scorbutus." Thus, some authors trace these terms to the Danish " Schorbeet, Schorbuck, Schoerbuch ; " others to the Dutch "• Scheurbuyk, Scheurbeck, Scorbeck " (ulcer of the mouth); others still to the old Saxon " Schorbock" (Reissen und Grimmen); and finally, others (particularly Lind) to the Slavonic " Scorb " (disease). The earliest mention thus far discovered of the German word " Scharbock " is to be found in the Botanologicon of Euritius Cordus (1534), where, in a passage on the remedial virtues of the lesser celandine (chelidonium minus), the writer says: " Saxones vero—(scilic. herbam dicunt)—Scharbockskraut, quod forte morbo, quern illi Sc/uirbock nominant, medeatur. 106 IMMERMANN.—SCURVY. Rochelle, 1671.— V. A. Moellenbroecl, De Cochlearia. Lips. 1074.—£. Ho.ruy, The Disease of London ; or, a new discovery of scurvy. Lond. 1675.—A. Mun- tingi, De vera antiquorum herba Brittanica, ejusdemque efficacia contra stoma- cacen seu scelotyrben, etc. 1081.— M. Lister, Tractatus de quibusdam morbis chronicis. Excitatio 5 de scorbuto. Lond. 1694.—H. Boerhaave, Aphorismi de cognoscendis et curandis morbis. Aph. 1148, etc., de scorbuto. 1708. (Com- ment, v. G. v. Swieten. Bd. III. Abth. 2. S. 389-465. Frankfurt und Leipzig, 1769.)—F. Hoffmann, Med. rational, systema. Halae, 1718. T. IV. C. l.—D. Sinopaeus, Parerga medica. 1734.—J. F. Bachstrom, Observations circa scor- butum, etc. 1734.—J] G. H. Kramer, Dissertatio epistolica de scorbuto. 1720- 1737.—A. Nitzsch, Theoret.-prakt. Abhandl. des Scharbocks. Petersburgh, 1747.—R. Walter, A voyage round the world in the years 1740-44 by Lord Anson. Lond. 1748.—H. Ellis, A voyage to Hudson's Bay, etc., in the years 1746 and 1747.—Lond. 1741.—R. M:ad, A discourse on the scurvy, annexed to Sutton's work on a new mode of extracting foul air from ships, etc. Lond. 1749. p. 437-450.—J. Pringle, Observations on the diseases of the army. Lond. 1752. J. Lind, A treatise on the scurvy. Edinb. 1753 (altogether the best of the older monographs on scurvy!).—J. a Bona, Tract, de scorbuto. Veronae. 1761.—X Hulme, De natur. caus. et curation. scorbut. libelli. Lond. 1708.—T. B. Sau- vage, Nosolog. methodic. T. II. Amstel. 1768.—O. V. Zeviani, Sopra lo scorbuto, etc. Veron. 1770.— U. B. Avkow, Diar. med. nav. in exped. Algir. Lond. 1774. —J. A. Brambilla, Chir. prakt. Abhandl. v. d. Phlegmonen, etc. Wien, 1775. Bd. II. S. 331 bis 354.—L. Rouppe, Observations on diseases incident to sea- men. Transl. from the Latin. London, 1772.—J. Hunczovski, Med.-chir. Bemerk. auf einer Reise durch England, etc. Wien, 1783.— W. Calien. First lines of the practice of physic. Edinburgh, 1791.—Jno. Clark, Observations on the dis- eases which prevail in long voyages to hot countries. Lond. 1809.—F. v. Schraut, Nachricht. vom Scorbut in Ungarn. "Wien, 1805.—J. D. Larrey, Me- moires de chir. militaire. T.I. Paris, 1812.— Ozanam, Histoire medicale gei.e- rale. Paris et Lyon, 1817.—II U. L. v. Roos, I. und II. med. Jahresbericht vom Marienkrankenhaus zu St. Petersburg. Petersb. 1836-1837.—Langheinridi, Scorbuti ratio historica. Berolin. 1838.—G. Samson von Himmelstiern, Beobacht. iiber. d. Scorbut, etc. Berlin, 1843.— W. Samson von Himmelstiern, Haser's Archiv. V. 4. 1844.— Cejka, Prager Vierteljahrschrift. I. 2. 1844.— Beer, Oest- reich. Jahrbiicher. Dec. 1844.—Becquerelet Rodier, Gaz. medic, de Paris. 1847. No. 26 und 1851. No. Sl.-Marchal, Gaz. med. de Paris. 1847. No. 34.—A. Fauvel, Archives generates de medecine. 1847. Juillet.—Andral, Union medi- cale. 1847. No. 78. —Christison, Monthl. Journ. of med. scienc. 1847. Jun., Jul. —Ritchie, Ibid. Jul., Aug. — Anderson, Ibid. Sept.—Landsberg, Henschel's Janus. Bd. 2. H. 1. 1847.—A. B. Garrod, Monthly Journ. 1848, Jan.—J". Henle, Rationelle Pathol. Bd. II. S. 2'6l.— Turnbull, The Lancet. 1848. April, June.— Bryson, Med. Times. 1850. May, June.— A. Lilienfeld, Casper's Wochenschrift. 1851. Nr. 1, 2, 3.—Forget, Gaz. med. de Par. 1853. No. 38, 39.—Paul, Allgem. HISTORICAL REMARKS. 107 med. Centralzeitung. 1857. Nr. 8.— Gallerand, Journ. de me*d. de Bruxelles. 1856, Mai.—M. Leudesdorf Allg. med. Centralzeitung. 1856. Nr. 80-82.— Wold, Vierteljahrschr. 1857. Bd. 9. S. 45 ff.—Le Bret, L'Union medic. 1857. No. 25. —Scrive, RCdat. med. chirurg. de la campagne d'Orient. Paris, 1857.—A Hirsch, Handbuch der histor.-geograph. Pathol. Bd. I. 521 ff. Erlangen, 1860. E. Opitz, Prager Vierteljahrschrilt. Bd. LXIX. S. 108 (1861).—X Duchek, Wiener med. Zaitschr. Bd. XVII. 1. S. 39 ff. (1861).— R. Krebel, Der Scorbut in geschichtlich-literarischer, pathologisch-prophylaktischer und therapcu- tischer Beziehung. Leipzig, 1862.—Hermann, Petersb. med. Zeitschr. Bd. V. S. 293 ff. (1863).— Kanicz, Wiener Med. Halle. Bd. V. 47, 48. (\8U).—Rlzet, Gaz. de Paris. 1864. 21.—Hammond, Military med. and surg. Essays, etc. Phila- delphia, 1864.—Barnes, Reports of the Medic. Officers of the Privy Council. 1864.—Duchek in Pitha und Billroth's Handb. der Chirurgie. Bd. I. 2. S. 273 ff.—A. Belpech, Annates d'Hygiene. II. Ser. T. XXXV. p. 297. (1871).—Greact, Ibidem. T. XXXVI. p. 279 (1871).—Dc.chambre, Gazette hebdomadaire. 2. Mars, 1871 (It. S5r. T. VIII.).—Legroux, Ibidem. No. 6.— G. Hayem, Ibidem. Nos. 14, 16, 17, 18 (1871).—Lasegue et Legroux, L'gpidemie de scorbut dans les prisons de la Seine etjl l'hopitalde la Piti£. Archives generates. VI. Ser. T. XVHT.— Daring, Deutsche Militararztl. Zeitschr. Bd. I. 7. S. 314 (1872).— Wolfram, Prag. Vierteljahschr. Bd. CXVIII. S. 112 ff. The preceding bibliography of scurvy is far from complete, and contains only the more important works on the subject. A more comprehensive enumeration may be found in Krebel's work (1. c), which devotes a hundred pages to the bibli- ography of the disease, and gives a list of all the works which had appeared up to 1861, with brief accounts of their contents. This list includes the names of no less than 773 authors! Historical Remarks. In the following brief historical sketch it is not our purpose to present an extended resume of this branch of our subject, but merely to point out those leading facts in the history of the disease which are important for a clear appreciation of its genesis. Although neither the medical nor the historical literature of antiquity and the earlier middle ages contains a single passage that discriminates scurvy as a distinct species of disease, or even positively indicates its existence during these periods, it is hardly to be supposed that an affection so closely connected, as scurvy appears to be, with certain widely prevalent sanitary evils—particularly improper diet, hardships, and unfavorable 108 IMMERMANN.—SCURVY. metereological influences—can have failed to manifest itself in all times whenever individuals or bodies of men have been sub- jected, under circumstances similar to those of recent times, to the influence of these noxious agents. So far, however, as his- torical evidence is concerned, the disease can be traced back only as far as the thirteenth century of the present era, and did not acquire actual historical importance as a frequent and wide- spread affection until about the middle of the fifteenth century, while its present name "scorbutus" made its appearance in medical and non-medical writings only at the beginning of the sixteenth century. Attempts have not been wanting to prove the existence of scurvy in ancient times from certain descriptions of disease by the older writers, which have been sup- posed to refer to the affection in question. None of the evidence, however, will bear careful examination—much of it having no bearing whatever upon the point at issue, while the rest is at least untrustworthy. The most conspicuous instance of this misrepresentation is that which pretends to recognize scurvy in the affection described by Hippocrates, and after him by Aretaeus, Celsus, Caelius Aurelianus, Paulus Aegineta, Avicenna, and others, under the term " 2n\r)ves /leydXnt (magni lienes);" still, as Hirsch has pointed out, there can be scarcely a doubt that these "enlarged spleens" are merely what is now known as the lesion of chronic malarial cachexia. The symptoms of scurvy were perhaps more closely simulated by those of a peculiar affection of the mouth called " SfceXortp^r;,1' or " 2ro/xa/A\ne fundamental cause, viz., the favorable change which has occurred in the exter- nal situation of the individuals, as for example, through the raising of a long siege, or the final arrival of the vessel in a safe harbor where a supply of provisions could be obtained, etc. It must be evident now, we think, from a retrospective sur- vey of this abundant material which has accumulated in the course of time in regard to the etiology of scurvy, that we have failed to obtain a uniform theory, or, in fact, any perfectly clear conception of the genesis of the disease. Not only does the affection seem to arise in different tvays in eliff'erent cases, but even where we have had more or less positive evidence of the direct agency of certain noxious influences, such as those men- tioned above, we have not always been able to point out their mode of action with absolute precision. In a subsequent chapter, after we have considered the symptomatology and morbid anatomy of the disease, we shall return to the results of our etiological inquiry, for the purpose of applying them, so far as is feasible, to an interpretation of the pathological process and its clinical manifestations. But for the present we may conclude here with the following summary of the conclusions—negative and positive—which we have thus far reached : 1. Scurvy is certainly not a contagious disease. 2. A miasmatic mode of origin is likewise clearly to be rejected for the majority of cases, but in many instances cannot be excluded with absolute certainty. 3. In many eases scurvy seems to be produced by the use of spoiled food and bad drinking-water. 4. The excessive use of salt is not an efficient cause of scurvy. 5. The majority of cases of scurvy are most probably due PATHOLOGY. 143 directly to a deficient supply of certain nutritive substances, which are more abundant in fresh than in salt meat, and are particularly abundant in green vegetables and potatoes. 6. It is probable that the immediate cause of scurvy in most instances is a deficiency of potash in the food, especially the potash salts of the vegetable acids. 7. An absence or deficiency of antiscorbutic food seems to produce the disease more readily when the demand for food is for the time being increased by external conditions (cold, damp weather, hardship), or when the vegetative functions are impaired by depressing influences of all kinds (lack of exercise, mental emotions, etc.). 8. There are, therefore, auxiliary causes of scurvy, and it is not improbable that these influences, when they are specially potent or when several of them act in combination, may some- times develop the disease in individuals or masses of men with- out the presence of the usual cause (the Rastatt epidemic, etc.). Pathology. General Description of the Disease. The beginning of scurvy is, as a rule, slow and gradual, and manifests itself for the most part by symptoms which at first do not bear the characteristic stamp of the later local phenomena of the disease, but are decidedly of a more general and indeterminate nature. These less pathognomonic changes in the general con- dition, as they usually appear at the very beginning of the disease, do, however, belong to the scurvy itself, and not to some prodromal cachexia of another kind ; since observation of the malady in its fully developed form teaches plainly that that initial general malaise lasts, without any material change, during the whole continuance of the scurvy—indeed, that it increases in intensity proportionally to the subsequent development of the localized symptoms. If this then constitutes an integrant part of the attack of scurvy, it must, on the other hand, be allowed that there are also cases of scurvv in which the disease seems 144 IMMERMANN.—SCURVY". to appear at once with the development of local foci, without serious initial general illness, and it is only later that the alteration of the general condition shows itself more plainly (Cejka). Yet such cases form decidedly the minority, and even in these the cachexia, as was just noticed, usually does not fail to manifest itself later. One may, therefore, be allowed to con- sider the existence of this latter, whether first developed some- what later, or, as in most cases, constituting a characteristic feature of the disease from its very beginning, as a peculiarity which almost constantly belongs to scurvy, or as an essential criterion of the pathological species (comp. Diagnosis). The evidences of this developing caediexia are, briefly stated, the following: Those attacked begin to complain of great weariness and depression, which gradually increase to such an extent that after even the slightest bodily exertion a feeling of complete exhaustion results, coupled with a sense of oppression in the chest, as well as with palpitation of the heart. This lessen- ing of the normal feeling of bodily vigor is regularly accompanied later by painful sensations in the voluntary muscles, at first with the character of the muscular pain which usually follows over- exertion of the body, but later with a more violent (rheumatic- like) character. These sensations annoy the patients principally in the day-time, and especially after rather active movements; during the night, on the contrary, as well as after long repose in bed, a temporary alleviation is often experienced. The pains are sometimes very variable as to locality, and then usually visit just those groups of muscles which were in activity shortly before ; sometimes, however, they are more fixed in their nature and are then localized preferably in the muscles of the small of the back and calves of the legs, which come specially into play in walking. Another pathological peculiarity of the scorbutic cachexia, which likewise often makes its appearance at an early stage, is the patient's great sensitiveness to a low temperature, in consequence of which he is very apt to complain of feeling chilly and manifests a disposition to seek warmth (for instance, in bed). Together with these sometimes painful, sometimes merely uncom- fortable sensations, there exists further, in most cases from the very beginning, a noticeable need of sleep, to which even in the day PATHOLOGY. 14,"i time the patient is often compelled to yield, without experiencing, however, a corresponding degree of refreshment. Furthermore, during their waking hours the patients show a changed psychical demeanor, which is marked by increasing apathy and indolence of mind, and chiefly by a spiritless and dejected mood, which is also usually not wanting in those cases of the disease in which the psychical depression is not fully explained by the wretched sur- roundings of those attacked (comp. Etiology). In regard to the need of food, individual cases of scurvy behave at the beginning of the disease quite differently. In some cases, for instance, the appetite disappears at an early stage, while in others it lasts longer, and may even in individual cases degenerate into a posi- tive voracity, characterized perhaps by a strong craving only for acid food. At other times all articles of food within reach of the patient, even though repulsive and decomposed, are gulped down with a greed that is positively unearthly. The feeling of thirst is usually not essentially changed so long as no fever exists. Simultaneously with these subjective derangements of the general condition, the appearance of the patients is for the most part also changed. The features fall in and are marked with a painful and sad expression, the eyes especially sink back more and more into their orbits and are encircled by broad, bluish- violet rings. The reddish tint, too, of the lips and cheeks gives place to a more cyanotic hue, and the mucous membrane of the mouth shows the same change in color. From day to day the skin shows an increasing pallor and earthy color, and in a few cases we may find, even in this prodromal period, brownish- colored spots of greater or less extent, with ill-defined outlines, on various parts of the face and body (Opitz) similar to those of bronzed-skin. The spots, once developed, generally outlast the hemorrhages and ulcerations of the skin which occur at a later date; and in those cases which terminate favorabty, they gener- ally lose their color only during convalescence. Another much more constant skin-symptom, which, moreover, hardly ever seems to fail when the disease is at its height, and as a rule is notice- able even in the prodromal period, is the remarkable dryness and brittleness of the epidermis, which is thrown off in scales like bran (pityriasis tabescentium). Still another characteristic pecu- VOL. XVII.—10 146 IMMERMANN.—SCURVY. liarity is the greater prominence of the follicles on the otherwise withered and flaccid skin, a peculiarity which will be most readily recognized by passing the hand over the extensor side of the extremities (Duchek). The temperature of the skin appears to the touch rather lessened than increased, but whether the inner temperature of the body experiences feverish augmentation at the very beginning of scurvy is more than doubtful, although for that matter accurate thermometrical observations of this period of the disease are wanting. It is, however, by no means probable that any increase of temperature of the body which might occur at this time could reach the degree of febrile move- ment often observed at a later stage. Besides the morbid changes just mentioned in the appearance and the condition of the skin, there will be observed, for the most part quite early, and often before the breaking out of the real local scorbutic symptoms, signs of a disturbed,—that is, of an impoverished general condition of nourishment; the heart's action, too, will be found to be feebler than natural. The muscles of the body lose their previous normal firmness, be- come flaccid and somewhat emaciated ; there is likewise gener- ally to be observed, even at this early period, a moderate de- crease of the panniculus adiposus, and therefore a corresponding decrease of the weight of the body. The arterial pulse becomes smaller and softer, and the contractions of the heart diminish in frequency. It is only after bodily exercise, as in persons suffer- ing from anamiia, that a more vigorous action of this organ mani- fests itself temporarily—this increased vigor being perceived by the patient as a feeling of palpitation, and by the physician as a more frequent and more vehement impulse of the heart. The frequency of respiration, which during repose is, as a rule, not essentially changed, may likewise, by the same causes, be in- creased to violent panting. A thorough physical examination of the heart and lungs, as well as of the abdominal organs, shows as yet nothing abnormal. The spleen, it should be re- membered, owing to previous or still existing intermittent fever, has been found enlarged in the prodromal period of scurvy; on the other hand, no enlargement of the spleen belongs properly to the disease, at least in its early stages. Just as little does PATHOLOGY. 147 the secretion of the kidneys at the commencement of scurvy seem to undergo any decided change. Finally, in regard to the duration of this initial period, this varies extremely, and may under certain circumstances be very long—that is, may last many weeks. Oftener, however, more decided symptoms of disease appear, even as early as during the first or second week, and lend a more serious aspect to the cachexia. The hitherto ill-defined picture of the disease assumes a more decided character, and shows the marks distinctly characteristic of scurvy. Moreover, it will be remembered that it was distinctly stated by us in the beginning that in many cases the initial stage may be only slightly developed, or even wanting altogether, and that in these, for the most part light forms, the disease is marked from its very commencement by the local symptoms which are now to be mentioned. In the majority of all cases the existence of scorbutic dis- ease is first proved in an unmistakable manner by the gums. That is to say, while usually during the prodromal period the whole mucous membrane of the mouth exhibits a bluish tinge, there is now developed on the edge of the gums, and especially on the outer side of the incisors, a zone of greater or less breadth within which the mucous membrane has a dark bluish- red tinge, and at the same time appears swelled and loosened in its connection with the teeth. All these changes are most pronounced on the pointed projections formed by the gums between the individual teeth, and which now begin to protrude more and more like puffy knobs. The swollen parts of the gums are at the same time quite painful; they bleed, too, very readily on touch or pressure of whatever kind; while, on the other hand, the rest of the mucous membrane of the mouth does not usually show abnormal sensitiveness or become at first the seat of bleeding. It is, moreover, characteristic of the scor- butic affection of the mouth at the beginning, as well as in its later stages, that, however much the painful swelling and red- ness of the gums may extend backwards from the region of the incisors upon the mucous covering of the eye-teeth and molars, yet all those places where teeth are wanting remain entirely unattacked ; so that, for instance, in the case of chil- 148 IMMERMANN. —SCURVY. dren with few teeth, or of aged persons, the scorbutic affection of the mouth is reduced to a minimum, or may indeed be entirely absent. On the other hand, in those places where only the stumps of teeth or merely the roots remain in the alveoli, the mucous membrane is attacked, just at if the row of teeth were perfect; indeed, it is precisely at such places that the affection often shows itself in an especially intense form. Finally, in proportion to the development and preponderance of the above-described changes do the patients begin to diffuse a nau- seous odor, which is not at first characterized by that carrion stench usually perceived in the exhalations of those suffering with scurvy in a more severe form or at a more advanced stage. Well-marked scurvy, however, does not invariably begin with the gums ; cases also occur in which, after a shorter or longer continuance of the prodromal period, or indeed without any such, other symptoms than the characteristic affection of the mouth are first observed, and it is only later in its course that the reddening and inflammatory^ swelling of the alveolar edge is added to these other pathological appearances of the disease. Thus, cases have been observed in which suggilations of the skin, bloody infiltration of the subcutaneous connective tissue (especially of the lower limbs), or even hemorrhages of the bowels, preceded the affection of the gums (Cejka, Duchek, and others). It must certainly be considered as a matter of some importance, in its bearing upon the question of the origin of scorbutic manifestations in general, that quite often the first evidence of serious local symptoms, while the cachexia was still but slightly developed, occurred preferably on precisely such parts of the body as had been exposed to an injury of some sort (mechanical or chemical), or on which at some previous time an inflammatory process had existed, and had subse- quently run its course. For instance, a very slight bruise, which in the case of a person in good health would hardly leave any trace, may lead, in the case of one suffering with scurvy which is still in the latent stage, to an extensive suggilation of the skin, and with this to manifest breaking-out of the disease; or, in another analogous case, the administration of a purgative may occasion not simply a diarrhoea, but even a pro- fuse enterorrhagia; finally, in a third case, the development of scurvy causes the ATHOLOGY. 149 granulation tissue in a wound to become spongy and to bleed easily. In all such cases the anomaly of the beginning of the disease consists in this, that in the case of individuals who have indeed, as a rule, a certain degree of cachexia, but as yet no scorbutic affection of the gums, local appearances of scurvy may occur at first on other parts of the body, while the affection of the mouth only occurs at a some- what later period of the disease. One circumstance, however, is common to all these cases of scurvy of anomalous commencement—namely, that a district of the body, which has been in some way injured or otherwise pathologically affected before, becomes the first seat of the disorder. Finally, in this connection it should be stated that, in a few cases of well-characterized scurvy, this affection of the mouth is completely absent during the whole duration of the disease, and that, too, notwithstanding the presence of teeth or the remains of teeth in the jaws. This anomaly, however, belongs to the rare exceptions ; the early and almost constant complication of the gums is the rule. Then again, there are a few cases—generally of a mild type —in which the affection of the mouth, coupled with a certain degree of general discomfort and weakness, is the only symptom which betrays the scorbutic nature of the disorder. In these cases, moreover, the disease may, by a timely change in the manner of life, good care, and proper treatment, be made to retrograde even at this early stage. In such an event not only does the general condition improve—the bodily and mental ex- haustion of the patient giving place to a normal feeling of strength and the expression of the face becoming more natural, but the affection of the mouth also often shows a surprising tendency towards recovery. The cedematous swelling of the edges of the gums diminishes and their livid redness disappears ; the parts also cease to be painful, and show no disposition to bleed; in a word, everything proclaims the restitutio ad inte- grum of the parts interested. More commonly, however, the disease pursues a different course. In the more severe forms of scurvy, and sometimes also in the lighter ones, after the cachexia is fully developed and the gums show the pathological changes already described, there arise still other local lesions in districts of the body which are, in an histological point of view, widely diverse. But before we 150 IMMERMANN.—SCURVY. submit these other local symptoms of the disease to a brief ex- amination, it seems necessary to give further consideration to the changes which the general condition and the affection of the mouth undergo in the more severe degrees of scurvy. If the case assumes a severe type, which generally then hap- pens when scurvy attacks those already diseased or incapable of resisting it, or when the injurious causes, described under the head of etiology, continue active during a long period and can thus develop their whole pernicious influence, then the weakness and prostration of the patients soon become extreme. They are unable to walk about and cannot even sit up; and while they are in such a condition of prostration, the mere attempt to lift them into the upright position may bring on a dangerous and sometimes even a fatal fainting fit. The pulse and the heart- beats both become reduced to a minimum of strength, and on auscultation of the heart systolic murmurs may now often be heard, as in the case of the most advanced stages of simple and of pernicious anaemia. Every movement, however slight, gives rise to the painful sensation of palpitation of the heart, accom- panied by dyspncea and a feeling of great oppression. The appetite is entirely absent; the thirst, on the contrary, is as a rule increased, owing to the fever which is now almost constantly present. The rheumatoid muscular pains have also increased in intensity and rob the patients of their rest at night—in short, all the subjective symptoms and functional disturbances which were present during the initial period have now very greatly increased and reached their highest degree. From the appearance of the patients and from their general condition of nutrition, it is clearly evident that they have reached a very high degree of cachexia. The features are greatly changed; the body seems emaciated, although it shows at the same time more or less dropsical swelling, especially on the lower limbs ; the skin is dry and flaccid, and the epidermis comes off in scales; in some places, too, it will be found to have lost its natural covering of hair ; finally, almost always the hemorrhagic spots, presently to be described, will be found scattered over a greater or less extent of the body. This disease, really terrible in the later stages of its progress, may in individual cases of intense scurvy be devel- PATHOLOGY. 151 oped from cases previously of a milder character, the change in type taking place sometimes very gradually, sometimes more abruptly. In the latter case, for example, the development of severe local symptoms often influences for the worse the patient's general condition in a very sudden manner. In severe and protracted cases of scurvy the diseased condi- tion of the gums increases both in extent and intensity in pro- portion to the increase of the general cachexia. The bloody and cedematous border of the gums, at first narrow, extends towards the roots of the teeth, and at the same time steadily increases in thickness. There are thus formed at last very bulk}-, spongy swellings, which are of an intense bluish-red color, bleed abundantly at every touch, and are for the most part very sensi- tive. In some cases these swellings may be so great as to com- pletely conceal the teeth. The act of chewing, which was already difficult before, becomes now almost impossible, especially if, as is often the case, the formation of a diphtheritic slough, or a diffuse ichorous disintegration, be superadded to the inflam- matory cedema of the gums. Where a diphtheritic slough has formed there will be observed along the upper edge of the gum, or on the summits of the swellings, lardaceous grayish-white deposits, which adhere closely to the mucous membrane, and when removed leave behind a bleeding excavation in the sub- stance of the gum. On the other hand, where a diffuse ichorous disintegration has taken place, the parts present the appearance of a slimy and extremely fetid mass, which, on being cast off, is discharged from the mouth mixed with abundant mucus. Where this latter process takes place, the roots of many of the teeth are often deprived of their covering of mucous membrane ; moreover, they may become loosened in their attachment to the alveoli, and finally may even fall out, after first becoming dis- colored and in some cases even carious. It is, however, remark- able that while in severe cases of scurvy the most serious changes always take place in the gums and teeth, the mucous membrane of the rest of the mouth participates, even at this stage, in so slight a degree. All the rest of the mucous mem- brane of the mouth, even when the gums are most severely attacked, shows, as a rule, only a livid color and moderate 152 IMMERMANN.—SCURVY. oedema—seldom a disposition to bleed, or severe inflammation, or real ulceration. If we pass on now to the consideration of the other local manifestations of scurvy, we shall find that the skin, the connec- tive tissue, and the muscles, are, next to the mucous membrane of the mouth, the parts most often affected by this disease, as well in the mild as in the more severe forms. Eruptions of a pronounced hemorrhagic character are among the characteristic manifestations of this disorder. They are usually developed in the later stages of the disease, though not unfrequently also in the earlier ones. These purpuric efflorescences are oftenest and earliest developed on the lower extremities, but are also observed, especially in severe cases, on the rest of the body (on the trunk, on the upper extremities, but comparatively very seldom on the face or on that part of the head which is covered with hair). They occur in part without apparent cause, in part as the imme- diate result of an injury to the skin, often of a very trifling nature. Among the hemorrhagic eruptions which have devel- oped spontaneously, the most numerous, as well as the most regularly found, are the small follicular petechia, which vary from the size of a hemp-seed to that of a lentil. These spots are of a roundish shape and at first of a dark bluish-red color ; they do not disappear on pressure, and are slightly or not at all prom- inent. Furthermore, as these spots are situated immediately over the hair-follicles, a hair or the stump of a hair will gener- ally be seen rising up through the centre of each spot. The color of the spots, which at first is bluish-red, afterwards passes gradually through a variety of hues—greenish, then brownish, etc. Quite often also in cases of scurvy, elevated efflorescences will be found, of the same color and size as the simple petechise maculataB. They seem to occur independently of any external cause, and many assume either the character of small nodules (Lichen scorbuticus, Lichen lividus, Acne scorbutica—Purpura papulosa), or that of small vesicles, filled with sanguinolent fluid (Herpes scorbuticus, Purpura vesiculosa). Apart from these various circumscribed forms of cutaneous hemorrhage, larger and more extensive extravasations into the tissues of the skin, and beneath the epidermis, occur much more frequently in PATHOLOGY. 153 scurvy than in any other form of hemorrhagic diathesis. In outward form these foci of disease present at one time the appearance of extensive blotches (ecchymoses) of irregular form, colored at first violet-red, later bluish-green, brownish, etc. ; at another, that of streaked extravasations of blood, or stripes (vibices) ; sometimes, also, that of vesicles of quite large size, filled with sanguinolent fluid (Pemphigus scorbuticus). These proruptions, the larger as well as the smaller ones, seem to occur by preference on the skin of the lower extremities. As the disease, however, advances further in its development, these interstitial hemorrhages of spontaneous origin occur also on other parts of the body. With the progress of the disease, too, the more readily does a trivial external injury produce suggila- tions of varying form and extent. Instances are known where a rather hard and somewhat uneven support has been sufficient to produce them in the arms ; they have also been produced in the buttocks by a crease in the sheet upon which the patient lay. In severe cases of scurvy almost the whole surface of the bod}^ except perhaps the face and head, may be covered with partly confluent, larger and smaller, newer and older, purpuric erup- tions, which naturally give to the patient an appearance as variegated as it is strange and alarming. Not always, however, do the cutaneous hemorrhages of scurvy patients appear under the clinical form of simple interstitial hemorrhages, or of simple inflammatory hemorrhagic exudations on the free surface of the corium; often the extravasation of red blood-corpuscles is only the prelude to, or a part of, more severe destructive processes which result in the formation of ulcerations of the skin. Pemphigus scorbuticus may, in the absence of all treatment, or where improper treatment is carried out, pass into a condition of ulceration of the skin—suppuration first taking place under the blackish crusts into which the vesicles have been converted, followed by a gradually progressing disintegration of the tissues of the skin (Rupia scorbutica). In cases which pur- sue a more favorable course, and especially if the patients receive an appropriate and timely treatment, the crusts fall off, without the skin having been destroyed beneath them, and all that re- mains to mark the spot is a temporary brownish discoloration. 154 IMMERMANN.—SCURVY. On the other hand, the peculiar ulcers of the skin (ulcera scorbu- tica) which occur with remarkable frequency when the course of the disease is malignant, do not always arise in the above de- scribed manner from pemphigous eruptions, but may also in cer- tain cases, without the previous formation of a vesicle, develop immediately from a simple hemorrhagic infiltration of the skin, which undergoes purulent breaking-down, or it may result from the breaking open afresh of recent and still highly vascular cica- tricial tissue of the skin. Finally, we sometimes meet with cases, as was incidentally mentioned above, where a so-called scorbutic ulcer, with its peculiarities which will shortly be noticed, is developed by speedier or more tardy metamorphosis from an ulcer of another description already existing ; this is likely to happen, for example, when the patient has meanwhile chanced to become affected by general scurvy. Now, although we should not be justified in asserting that scorbutic ulcers of the skin possess pathognomonic characteris- tics—that is, characteristics which are observed only when scurvy exists—still these ulcers present features which are, to a certain extent, characteristic of the disease. These special features are more easily recognized in all those cases in which several such ulcers are developed on the patient at the same time or in quick succession, and thereafter pursue nearly the same course of development. These ulcers vary in size (sometimes being as large as a thaler or even as the palm of the hand), and extend in depth through the corium. They are covered with a brownish- red or blackish tough scab, on the removal or dropping off of which there appears sometimes a foul, ulcerate^, surface covered with shreds of tissue stained with blood, sometimes a spongy and easily bleeding surface of granulations ; in both cases the ulcerated surface secretes a considerable quantity of thin, san- guinolent fluid, often of an ichorous character, and then of highly offensive odor. These ulcers are, moreover, generally surrounded by a broad halo of a dirty violet color; they show little tendency to cicatrize ; on the contrary, they are apt to spread both in extent and in depth. In the latter case the ulcerative process may involve some of the larger vessels of the skin, and so give rise to copious and even fatal hemorrhages. PATHOLOGY. 155 Apart from this, however, these ulcerations exert a very delete- rious influence on the general condition of nutrition by the pro- fuseness of the secretion connected with them. The painfulness of these scorbutic ulcers is, as a rule, not very great; still, it contributes its share to the subjective discomfort of the patients. We mention, finally, the fact that the above-described changes in the skin (hemorrhages, hemorrhagic inflammations, and ulcerations) may also occur in the immediate surroundings of the nails. The latter, then, sometimes show simply an extra- vasation of blood beneath them ; sometimes, however, if an inflammatory or ulcerative process has attacked the root or bed of the nail, they may turn brownish-yellow, die, become loose, and at last be thrown off, either wholly or partially (Paronychia et Onychia scorbutica). After the gums and the outer skin (the nails included), the scorbutic attack localizes itself most frequently in the subcuta- neous and deeper layers of connective tissue, as well as in the muscles and intramuscular tissue. These foci of the disease also appear to be located with special frequency on the lower extremities, and in mild cases are indeed entirely limited to these parts of the body. In the more severe forms of the dis- ease, on the other hand, they are observed not only in greater number, but also of greater extent; they are also found on other regions of the body. The loose tissue near the tendo Achillis and that in the hollow of the knee, and further the muscles of the calf of the leg, must be mentioned as the chief localities spe- cially chosen by the scorbutic affections of the connective and muscular tissues ; besides these, however, the subcutaneous tis- sue of the posterior surface of the thigh, as well as of the arm- pits, and, among the muscles, the recti abdominis, the lumbar muscles, and the pectorales majores, are comparatively often attacked. Moreover, in what has just been said, it is by no means intended to convey the impression that other layers of the connective tissue of the body, or other portions of its muscular tissue, may not now and then be found affected by scorbutic processes. Now, in regard to the outward form of the affec- tions of the connective tissue, these present themselves as swell- ings, which are at first soft, but later usually become as hard as 156 IMMERMANN.—SCURVY. a board. The limits of these swellings are in some cases sharply defined, in others less so; the skin over them is not movable, and is variously colored, according to the mode of origin (com- pare what follows), the time of duration, and the deeper or more superficial site of the focus. The induration may, under circum- stances favorable to its development, become very extensive, so that, for instance, at times a considerable portion of a limb (the whole calf of the leg, more than half the thigh, etc.) will be affected by it, and more or less swelled. The manner of origin is not always the same, since these foci are sometimes developed acutety, and then, for the most part, with pains and fever ; sometimes gradually, and in this case usually without pain and without fever. If the mode of development be an acute one, there will be noticed, as a rule, on the painful part, which is beginning to become indurated, a very vivid redness of the skin which covers it; this is, moreover, hot to the touch, swelled, and shining. After a few days, the redness, swelling, and pain- fulness having in the meantime diminished, the skin assumes a brownish tinge, and the epidermis begins to scale off, the latter process being usually repeated several times. Finally, a discoloration, which is apt to last a considerable time, marks outwardly the site of the recent or even still active subcuta- neous focus of disease. In other cases, where the infiltration of the subcutaneous connective tissue has taken place in an acute manner, the superjacent skin undergoes a livid discolora- tion, grows thinner and thinner, and finally ruptures. From the ulcerated opening thus formed, large quantities of bloody matter, mixed with shreds and sometimes gangrenous masses, are then usually discharged, and a foul ulcer remains, offering in its further course the above-described characteristics of scor- butic ulcerations of the skin. If, on the other hand, the process takes place more slowly, without either pain or fever, the hyper- baric redness and the swelling of the skin covering the part will be absent; there will also be no subsequent scaling off and brownish discoloration of the same. On the surface of this swell- ing, which at first is soft, but subsequently becomes hard, there is merely to be perceived a bluish, greenish, or slightly yellowish tinge, according to the more superficial or deeper site of the PATHOLOGY. 157 focus. The functions' of the neighboring parts, especially the muscles and joints, is naturally very seriously affected by these indurations and tumors of the connective tissue, and, as the usual site of these foci is on the extremities, the power to use the latter, even in those cases in which no serious pathological lesions have occurred in the muscles themselves or in the cap- sules of the joints, is often materially diminished. It is not a rare occurrence, however, in scurvy, for the muscles of the extremities to be the seat of localized inflammatory processes, which may develop either at the same time with the subcuta- neous connective tissue foci described above, and as a direct extension of the latter process, or even quite independently. In the former case it is not possible to recognize the existing affec- tion of the muscles by any special clinical signs observable dur- ing the patient's lifetime, nor indeed in any other way than by an autopsy. In the latter case, on the other hand—that is, if it arise independently—the localized disease of the muscle is characterized by the presence of a hard mass, which is more or less sharply defined, sometimes painful, sometimes indolent, but upon which the skin, whose color has undergone no change, is perfectly movable. For the rest, the circumscribed scorbutic affections of the muscles show a great analogy with the similar affections of the connective tissue in the following particulars: they occur at one time as acute processes with fever, at an- other as subacute or chronic without fever; they are, more- over, naturally accompanied by a decided impairment of the functions of the muscle attacked. The pathological processes and histological changes, which lie at the foundation of the scorbutic affections of the connective and muscular tissues, will be more thoroughly considered farther on ; we will, therefore, here only remark in passing that in both these tissues we have to do in part with simple hemorrhagic infiltrations of non-in- flammatory nature, in part with hemorrhagic inflammations. In our description, thus far, we have in general portrayed those features of scurvy which are observed in the greatest number of cases, the mild as well as the severe ones, and which might fairly be considered as the principal characteristics of the disorder, either in its partially developed or in its fully devel- 158 IMMERMANN. —SCU RV Y. oped form. In many cases of scurvy'either recovery takes place, or the disease terminates fatally, under manifestations of increasing general weakness, without the development of any further local symptoms on any part of the body. As we shall describe farther on the changes which are observed at the autopsy in those cases that end fatally, it is plainly our best course at present to describe next in order, as briefly as possible, the retrograde changes that take place in those local manifesta- tions of the disease (in the gums and teeth, skin, connective tis- sue, and muscles), which have already been referred to. In these cases, some of which may be even quite severe, the recov- ery may be either complete or incomplete. In cases where the affection of the gums has been intense, but yet not of a diphtheritic character nor associated with ichorous disintegration of the mucous membrane, the swelling and red- ness, under appropriate treatment, may gradually disappear, and in the course of time the parts may return to their natural condition, the edges of the gums becoming again adherent to the teeth. This return to the natural condition, however, requires many weeks, and often months. Again, the restoration may be incomplete ; a hyperplasia is very apt to take place during the stage of convalescence, in the still red and swelled gums, as a result of which they generally remain thickened and indurated during the remainder of the patient's life. These permanently swelled gums, however, do not usually cause the patient any really serious annoyance. Diphtheritis of the mucous membrane which surrounds the teeth, and, still more, fully developed dif- fuse ichorous degeneration of the same, leads directly to more or less extensive losses of substance of the mucous membrane, which, in favorable cases, are gradually filled up later by the formation of granulations and cicatricial tissue, and may at length be entirely healed. In such cases the teeth may escape damage altogether, or some of them may fall out. Among the cutaneous processes, the petechias, ecchymoses and vibices grad- ually disappear within a few weeks. The scorbutic ulcers of the skin, on the other hand, take the following course : the granula- tions, which at first are flaccid and bleed easily, become firmer as.soon as the patient's general condition improves ; the secre- PATHOLOGY. 159 tion, moreover, loses its thin, sanguinolent character, and becomes more and more like good ordinary pus ; finally, after a certain length of time, the loss of substance is made good by the forma- tion of a brownish-red, dark-colored cicatrix. The indurations of the connective tissue, even where the swelling was very exten- sive and hard, may in favorable cases gradually grow softer and disappear ; yet frequently the last remains of these indurations only disappear after the patient is far advanced towards recov- ery, and when his general condition leaves nothing to be wished for. In other cases there remains for years, or even for life, an abnormal resistance of the parts which were the seat of these indurations—a result which indicates that a hyperplasia of the connective tissue has taken place at the point of previous scor- butic attack. If these firm masses of callous connective tissue are situated upon or in the neighborhood of the fleshy parts of muscles, there results secondary atrophy and lasting functional impairment of these latter; if they are, as is often the case, sit- uated near to joints, they occasion for a long period, or even for life, a so-called false anchylosis—the immobility of the joint being due to the fact that the tendons, which pass close to it, are enveloped by the growth, or that they form adhesions with the bones that compose the articulation. Such stiffness has been seen to remain, after scurvy in the knee-joint, owing to the pres- ence of indurations in the popliteal space ; and in the ankle-joint, owing to the presence of indurations near the tendo Achillis. Among the forms of immobility of the latter joint observed most commonly at the clinique, are those known as pes equinus, pes valgus, and pes varus—the two latter being of less frequent occurrence than the former. Finally, the hemorrhagic foci in the substance of the muscles generally end in gradual resorp- tion ; more rarely there remains (in consequence of an abnormal growth of connective tissue and the formation of a cicatricial callosity) a hardness in the muscle attacked, which is, moreover, in such cases naturally shortened, and becomes the seat of a lasting, more or less pronounced, contracture. In contrast to the forms of scorbutic disease which have been thus far described, and in which the disease, although severe and sometimes even fatal in character, yet remains limited in 160 IMMERMANN.—SCURVY. its local manifestations to the parts of the body already men- tioned (gums, skin, connective tissue, muscles), there are other forms which are to be looked upon as more severe than the fore- going in this one respect, viz., that the localizations are more varied in character, and especially that they involve to a greater or less extent other regions, organs and tissues of the body than those already named. It may be well at this point to remind the reader that if at the bedside we are apt to find the type of a disease somewhat different from that which is pictured in the text-books, this is especially true of all the different ff7ms of scorbutic disease. In our further consideration of scurvy, therefore, it will be impossible for us to give a comprehensive description of the general course of this affection in its more unusual forms ; we must simply limit ourselves to a short enu- meration of those parts, organs and tissues in which changes of a distinctively scorbutic character have been observed. The mucous membrane of the nasal cavities is not unfre- quently the seat, in severe cases of scurvy, of serious and dan- gerous epistaxis, which occurs at times spontaneously,—more often, perhaps, on too violently blowing the nose. These attacks of bleeding at the nose, which for the most part cannot be suc- cessfully combated without plugging the nasal passages, are considered, and have been long considered, as a very ominous symptom,1 owing to the exhaustion which they occasion. Pro- fuse hemorrhages from the stomach are sometimes observed ; they appear under the form of a more or less abundant haema- temesis, which may at times be ushered in by a very marked sense of oppression in the region of the heart (Duchek). Hemorrhages from the bowels and copious bloody stools occur more frequently; they are ver}7 apt to follow the admin- istration of the active purgatives (compare above), although in other cases they result from a dysentery which, having existed previously, has been modified by the scurvy (compare Special Symptomatology and Complications). These bloody 1 Compare the passage already mentioned in Joinville's Histoire de St. Louis, which Bpeaks of the epidemic of scurvy in 1249, in the army of St. Louis of France : " le signe de la mort etait tel, que la, od le nez saignoit, il falloit mourir." PATHOLOGY. 161 dejections often lead, if very abundant, to rapid exhaustion of the patient, and to death in the course of a very few days ; at times the}- continue somewhat longer, and perhaps even for several weeks in succession the patient may pass per anum, sev- eral times daily, sanguinolent masses of a most putrid odor. Hematuria also sometimes occurs in severe cases of scurvy. On the other hand, hemorrhages from the respiratory organs are of rare occurrence, and are for the most part only observed in the case of those who are already affected with incipient phthi- sis, and are consequently already predisposed to haemoptysis ; or in cases where the scurvy becomes complicated by a pneu- monia, hemorrhagic infarctions, or gangrene of the lungs. In general, all these hemorrhagic accidents, which occur in the course of an attack of scurvy in the various canals and open cavities of the body, contribute in a very great degree to aggra- vate the patient's general condition ; they are to be considered, therefore, under all circumstances, as very dangerous symptoms. Of an equally serious nature are the localizations in the serous membranes, especially the pericardium and pleura. These local affections, which are not of rare occurrence in the more severe forms of scurvy, are developed often in a wonder- fully short space of time ; they are ushered in by fever, and con- sist of inflammatory effusions of an hemorrhagic character (peri- carditis, or pleuritis exsudatoria sanguinolenta sive scorbutica), which are clinically marked by the well-known physical signs of pericarditic or pleuritic exudations, and which by their quan- tity occasion, as a rule, great hinderance to the functions of the heart or lungs, as the case may be. These effusions in severe cases often hasten the end where patients are lying already in a state of complete prostration ; in other cases, too, they lead quite directly, of themselves, to death, breaking in suddenly upon the patient, who had up to this time been in a fair general condition, and by their violence and rapid develop- ment very shortly endangering life. Of the greatest interest, on the other hand, is the fact noticed by a few observers (F. v. Niemeyer), that even very abundant and suddenly occurring effusions into the thoracic or pericardial cavity, in the case of scorbutic patients, may sometimes be absorbed with almost VOL. XVII.—n 162 IMMERMANN.—SCURVY. equal promptness, if a timely and energetic treatment prove successful in improving the general condition. Affections of the bones, cartilages, and articulations are among the peculiar complications sometimes observed in the more severe forms of scurvy. The periosteum of the long, hol- low bones of the extremities is most often affected, especially that of the tibia on its anterior surface ; further, the periosteum of the ribs, of the scapula, of the inferior maxillary, as well as of the palatine process of the superior maxillary bone. These affections of the periosteum, which are generally circumscribed in character, occur relatively often as the result of some me- chanical injury (a blow, concussion, etc.) that has befallen the bones ; they also sometimes occur without any apparent cause. On the surface of the bones above-named, as well as sometimes on other bones of the skeleton, there are formed painful swell- ings of varying size and of a certain degree of hardness, which owe their origin to simple hemorrhages or to inflammatory hemorrhagic effusions under the periosteum (periostitis scor- butica), and which, even in favorable cases, are usually reab- sorbed only very tardily. The bone itself usually remains intact so long as these swellings of the periosteum do not exceed a certain size, and provided the general condition is early im- proved ; in unfavorable cases, however, and especially if the periosteum be separated from the bone throughout a consider- able extent, partial necrosis of this latter, with subsequent exfoliation and expulsion of the dead portions, is very apt to follow. In other cases, again, the epiphyses of the bones become swelled and painful, and at a later stage the cartilage may become partially or even wholly separated from the ends of the bones—a process which has been especially observed on the ribs, sometimes even affecting several of these bones at once. In such cases there is formed, on one or on several ribs, a swell- ing of the anterior extremity, painful especially on pressure or on the movements of respiration; later there will be developed an angular bend at the point of junction of the rib with the costal cartilage; still later, abnormal mobility and crepitation at this same point; and finally, complete separation of the car- tilage from the rib. After this separation, the anterior extremity PATHOLOGY. 163 of the rib, deprived of its connection with the sternum and without support, now sinks back, while the detached end of the cartilage appears prominently under the skin. Reunion may afterwards take place by reabsorption of the blood and other fluid matter extravasated between the two parts, but they rarely resume their normal position. As a matter of fact, the patients succumb before this can take place, as the affection in question is usually only developed in extremely severe cases (Duchek). Finally, among the scorbutic affections of the bones must be enumerated the softening of the callus of uniting or long united fractures, described by some authors (Aitken, Pringle, Bell, Leveille, Krebel). This softening is accompanied by swelling and painfulness of the parts involved, and has been observed in a number of very severe cases of scurvy. In regard to the scorbutic affections of the articulations, these occur sometimes as independent local affections, sometimes as accom- paniments of periarthritic processes going on in the neighboring connective tissue. In both cases we have to do with serous, or much more often with hemorrhagic effusions into the cavities of the joints, the process being characterized by great painful- ness and constantly increasing swelling of the joint, by active fever, and by the appearance of fluctuation. These effusions, however, if the general disease takes a favorable turn, may, like the effusions into the serous cavities (compare above), also be quickly reabsorbed ; it rarely happens that they lead to actual anchylosis. This arthritis scorbutica, for which, as a rule, no special immediate cause could be assigned in the cases reported, has been observed most often in the knee- and ankle- joints, but also in the hip-joint, shoulder-joint, and in the artic- ulation of the jaw. As very rare local affections of scurvy are to be considered the isolated cases of inter meningeal hemorrhage, which usually ran their course under the form of rapidly fatal apoplexy, but also in some cases led to death with the appearances of grad- ually augmenting compression of the brain: headache, dullness, and finally stupor. It is still doubtful whether or not hemor- rhages occur in the substance of the brain; at all events, the remarkable case described by Opitz might have been pointed to 164 IMMERMANN.—SCURVY. either as a case of scorbutic hemorrhage into the brain, or as one of an acutely developed hamiatoma of the dura mater which subsequently was reabsorbed, or as one of hemorrhage into the pia mater which remained circumscribed. As the patient recovered, it was not possible to determine which of these three suppositions was the correct one. In the case of scurvy to which we have just referred, convulsions suddenly occurred, followed by loss of consciousness, and hemiplegia of the (left) side of the face and body. Twenty-four hours later the sensorium had become clear again, and the paralysis had disappeared. A moderate degree of headache per- sisted still for some time, and there was also a slight hypersesthesia of the affected upper extremity, which lasted about two weeks; later these symptoms also dis- appeared, and finally the patient entirely recovered from his scorbutic attack. Finally, among the scorbutic local affections which are not of such very rare occurrence, should be mentioned the affections of the eye and its accessory organs. Thus, there is sometimes developed, in mild as well as in severe cases of scurvy, an inflam- matory process in the conjunctiva of the bulb, as well as of the eyelids (conjunctivitis et blepharitis scorbutica),—a form of con- junctivitis which shows, besides the usual manifestations of this affection (redness, swelling, and increased secretion), those characteristics which stamp it as being scorbutic in its natures Thus, for example, at an early date, more or less extensive extra- vasations of blood are pretty sure to make their appearance under the conjunctiva, raising the latter up in many places and causing it to protrude in the form of little sacks filled with blood, which may be sufficiently numerous to cover the whole anterior surface of the eye. In cases which pursue a favorable course, there follows later a gradual reabsorption of the extrava- sated blood, with disappearance of the inflammatory symptoms. At other times, in addition to the conjunctivitis—or even inde- pendently of this—hemorrhages take place into the anterior cham- ber of the eye, and these often seem to be dependent upon an inflammatory affection of the iris (iritis scorbutica). This latter affection may entirely disappear, or may lead to an abnormal attachment of the iris to the anterior surface of the capsule of the lens. The extravasated blood is either quickly and entirely reabsorbed, or portions of the same remain for a considerable time pathology. 165 in the form of brownish-red spots on the surface of the lens, interfering more or less with the power of sight. The occurrence of hemorrhagic chorioiditis has also been asserted ; and finally, sometimes, in very severe cases, which so far have always ended fatally, there arises, in the course of a fully developed general cachexia, a panophthalmitis (generally double), in the course of which the cornea becomes rapidly opaque, and may even undergo ulceration, as a final result of which the eye is completely de- stroyed (G. v. S. Himmelstiern). We shall not here go into fur- ther details in regard to these quite numerous affections of the eye which are observed in the course of scurvy ; for further par- ticulars regarding these, we refer our readers to the works of Thielmann l and Krebel,2 as well as to the text-books of ophthal- mology. To close our general examination of the course and manifes- tations of scurvy, we shall still mention some pathological facts, which, indeed, do not possess that specific clinical character that appertains to the local symptoms hitherto considered, but which nevertheless may prove of value by leading to a clearer under- standing of the nature of the disease. Among these facts may be mentioned : 1. The frequent occurrence of enlargement of the spleen during the later stages of the more severe cases of scurvy, —an enlargement which has been verified during life (and also on post-mortem examination) independently of any malarious affection ; then 2. The frequent occurrence of albuminuria in the more intense cases of scurvy of every sort. Where autopsies were subsequently made, no advanced or even clearly developed affection of the kidneys was by any means found always to correspond with the existence of this latter symptom ; these organs, on the contrary, were not seldom found apparently intact (Opitz, Duchek, and others). Interesting, but in a theore- tical point of view perhaps somewhat overestimated (comp. what follows), are further, 3. The statements of Duchek in regard to the comparative quantities of the various normal elements of the urine in the case of a number of scurvy patients carefully examined by him for this purpose. It was found, for example, 1 Die scorbutische Augenentzundung. Med. Zeit. Russl. 1844. Nr. 1 u. 2. 2 L. c. S. 179-18G. 166 IMMERMANN.—SCURVY. that with the increase of intensity of the scorbutic disorder in general, not only was there a decrease of the amount of urine secreted, but also a decrease of all the solid elements of the urine with the exception of the potassa (and of the phosphoric acid) ; while vice versa, as improvement occurred in the scorbutic symp- toms, the urine'again increased in quantity, and at the same time the normal quantitative relations between the solid elements of the urine were restored. We shall return again to this matter farther on, and only give here very summarily the evaluations stated by Duchek: Duchek's ' examinations were conducted in the cases of six scurvy patients. In the first period of the disease the quantity of urine passed in twenty-four hours fell to 1500-1200 cubic centimetres—in one particularly severe case as low as 830 cubic centimetres; further, the specific gravity fell to 1015-1009. Specially notice- able was the want of proportion between the amounts of potassa and of soda secreted in the first period, since, white the former remained almost the same as under normal conditions, and in three cases even increased somewhat, the latter decreased so much and so quickly that, in place of the normal proportion of 1 : 12 between the two alkalies (potassa and soda), the proportion was now on an average 1 : 1.9. On the other hand, during the second period of the disease the secretion of potassa experienced a slight absolute lessening. Finally, it has again and again been mentioned in the course of this article that many local affections of scurvy may run their course vtith fever. In opposition, however, to these results of observation, it must be remarked that the temperature of the body is not influenced specially by general scurvy, at least not to the extent which would justify us in designating the increase as fever. On the contrary, when the temperature during scurvy reached a fever point—and this occurred in fact in almost all severe forms of the disease at some time or other—then there always existed at the same time such local processes (of an inflammatory nature) as would in all probability have induced fever even in non-scorbutic patients. Post-mortem Appearances. The bodies of those who have died of scurvy show, as a rule, slight rigidity, early decomposition, and extensive cadaveric 1 Oestr. Jahrbiicher. 1861. Bd. XVII. S. 39. POST-MORTEM APPEARANCES. 167 spots ; they appear, moreover, emaciated in varying degree (ac- cording to the duration of the disease), though at the same time there is often dropsical swelling, especially of the lower limbs. The skin is usually of a dirty grayish-yellow color, dry and leathery to the touch, and covered with abundant epidermis scales. On the trunk and extremities (almost never on the face) are to be seen, varying in number, size, form, and topographi- cal distribution, the hemorrhagic eruptions of the skin, already described on a previous page. A more careful microscopical examination of the parts so affected shows that, in the case of the smaller (petechial) forms of purpuric eruption, the extra- vasation of blood almost always proceeds from the very close and fine network of capillaries surrounding the hair-follicles, since the extravasated red corpuscles of the blood are only found deposited in the meshes of this network and in its immediate neighborhood. The larger hemorrhagic eruptions (ecchymoses, vibices) are naturally occasioned by more extensive extravasa- tions of blood, which will be found at one time to have ema- nated from the more superficial, at another from the deeper capillary network of the corium. The hemorrhagic foci existing in the more homogeneous and compact upper layer of the corium (pars papillaris corii) are, as a rule, less spread out in surface than those which are more deeply situated in the laxer tissues of the pars reticularis corii; but the former are almost always complicated by the entrance of blood into the deeper layers of the epidermis, especially into the so-called rete Mal- pighi. Microscopical examination teaches that it is not only in the case of vesicular and bullous eruptions (purpura vesicu- losa—pemphigus scorbuticus) that the blood extravasated from the superficial capillaries of the skin becomes collected on the surface of the papillae, but that the same process, on a much less extensive scale, goes on also in the macular forms of purpura, since in these, too, it will be found that the rete Malpighi has been invaded by the red blood-corpuscles (Opitz). Now, whether the cutaneous hemorrhage has been superficial or deep-seated, we shall find—if, as is usually the case, it is of quite long stand- ing — that only very few of the blood-corpuscles which are deposited in the rete and corium are well preserved, the greater 168 IMMERMANN.—SCURVY. part of them having begun to disintegrate and to lose their color- ing matter in a greater or less degree. It will be found, too, that the neighboring tissues have, as a rule, imbibed this coloring matter, or it has been deposited in separate particles here and there among the tissues in the form of small grains, lumps, or flat pieces of various colors (yellowish-red, brownish, black).—In regard to the coarser anatomical characteristics of scorbutic ulcers of the skin, we refer to what has been already stated by us in the description of the disease ; no very accurate histologi- cal descriptions of the behavior of the edge of the ulcer, of the granulations, etc., are to be found in the literature of scurvy up to the present time. Those indurations of the subcutaneous connective tissue, and of the deeper layers of connective tissue, which have been recognizable by palpation during life, prove at the autopsy to be infiltrations of the tissue by extravasated blood which has coagulated, and the color and condition of which depend upon the recentness of the extravasation. These infiltrations present different characteristics: some are rather firm, some softer in consistency ; some are sharply defined, and may then in some cases even be enucleated, while the limits of others are less clearly marked. In the more recent foci there will still be found a dark cherry-red or brownish-red cruor of gelatinous consistency in the midst of a clearly distinguish- able network of fibres of connective tissue, which are of a yel- lowish or reddish hue ; on pressure or section a reddish serum may be caused to exude from the clot. In the case of foci of older date, on the other hand, we have yellowish-brown or gray- ish-yellow, firm and homogeneous deposits of fibrine within which the tissue-elements (fibres of connective tissue) can only be found with difficulty. In still later stages, and in the case of such extravasations as were apparently beginning to be dissi- pated during life, the still existing fibrinous masses will be found to have again become softer and more friable, yet at the same time more decolorized than before ; and the network of connec- tive tissue, which could previously hardly be distinguished, will now be found to be more plainly recognizable and of gelatinous consistency. Finally, if the mass represents a focus of ancient date, which has at the same time retained its hardness, then, on POST-MORTEM APPEARANCES. 169 cutting into it, the knife encounters an almost cartilaginous resistance, and, as a rule, meets with callous masses of connective tissue of a yellowish or brownish color, but no longer any fibrin- ous clots and sanguinolent infiltration. If extensive callous solidifications of this sort have taken place in the subcutaneous, subfascial, and intermediate connective tissue, then the muscles lying beneath or imbedded in this tissue are seen to be atro- phied ; their tendons are often abnormally attached to the bones, or are, as it were, actually walled up in the fibrous tissue, and the joints to which they belong are by this means often brought into a condition of so-called false anchylosis. Thus are to be explained, for instance, those displacements of the osseous parts composing the ankle-joint which are known under the names of pes equinus, pes valgus, and pes varus (comp. Description of the Disease). In regard to the more recent foci in the muscles, it must be said that the anatomical changes which characterize these are similar in every respect to those of the more recent foci in the connective tissue, since here, too, we have to do with infil- trations of extravasated blood into the fleshy part of the mus- cles. That portion of the muscle which is thus impregnated with clotted blood appears of a dark cherry-red or even blackish color; it is, moreover, somewhat hard, yet much less firm than the muscular tissue which remains in its normal state, and may for this reason be easily crushed by careless handling. On the other hand, in the case of muscular foci of older date and which have not become resolved, we find, as in the case of lasting indu- rations of the connective tissue, on section of the shortened and much atrophied muscle, at the point where induration could be felt, scarcely anything besides callous cicatricial tissue. Much less uniformly do we find, at the post-mortem exami- nation of those who have died of scurvy, lesions of the articula- tions and bones, in addition to those which have been described of the skin, the connective tissue, and the muscles. Sometimes, however, on opening one or another articulation which has been found to be swelled, there flows out a serous or a sanguinolent fluid from the opened cavity, whose walls (cartilage, capsular membrane) may then on examination prove to be in a normal con- dition, or may appear more or less severely affected. The latter is 170 IMMERMANN.—SCURVY. very likely to be the case where the effusion is hemorrhagic in character, in which event there will pretty often also be found partial ulcerations of the capsule of the articulation, effusion of blood between the cartilage and the epiphysis of the bone, sepa- ration of the cartilage, and pulpy softening of the ends of the bone under the same. The following may also be mentioned as among the lesions which are sometimes observed in the bones : collections of clots of blood, or of sanguinolent jelly-like sub- stance between the periosteum and bone, separating the perios- teum from the bone, and complicated for the most part by par- tial necrosis and softening of the bone, and frequently, too, by ulceration and degeneration of the periosteum itself; further, detachment of the tendinous insertions of the muscles from the bone thus altered and diseased ; finally, extravasations within the bone, especially in the midst of the spongy tissue, which is at such points almost always more or less softened, and has been at times found to form a deliquescent, gelatinous mass. Now, in regard to the remaining parts, the mucous membrane of the mouth, in the first place, must be again shortly considered here. As a rule, in cases of scurvy which have terminated fatally, the gums of the cadaver show still more plainly and visibly those phenomena of extreme swelling, of diphtheritic sloughing, or of ulceration, which had been observed during life. Only the redness is less pronounced than during life, since this is in part owing to an active congestion of the vessels of the mucous membrane, which naturally disappears at death ; while, on the other hand, the condition of hemorrhagic infiltration of the mucous membrane, and the lividity of the same caused by this, is particularly distinct, both to the naked eye and on microscopical examination, owing to this same (post-mortem) absence of congestion. A microscopic examination shows, indeed, that the whole of the diseased tissue is more or less thickly studded with the red corpuscles of extravasated blood. If the case under examination be one of older date, which has run a long course, the thickened gums may be found compact, firm, and nodular; a careful examination shows that this depart- ure from the usual state of things is occasioned by a new forma- tion of connective tissue, which has taken place in the gums POST-MORTEM APPEARANCES. 171 after they have been infiltrated with blood. The rest of the mucous membrane of the mouth shows in scurvy, on the cadaver as well as during life, but slight alterations ; its color is for the most part somewhat bluish, and it is only rarely that it presents more serious lesions in the form of hemorrhagic infiltrations or ulcerations with loss of substance. Among the organs of the thorax, it is the pericardium which is most frequently attacked, and next to that the pleura. In one or more (sometimes even all three at once) of these serous sacks, considerable effusions of a fluid, either clearly sanguine or at least stained with blood, will often be found. The quantity of this fluid, as we have just remarked, is frequently very great, and may, for instance, in the pericardium alone, amount to sev- eral pounds. In addition, however, to these exudations, evi- dences of inflammation are also pretty constantly found in the serous membranes, namely, increased injection of the vessels, fibrinous deposits, and finally hemorrhagic spots, which owe their origin to an extravasation of blood into the tissue itself of the pericardium and pleura. Ecchymoses of this sort are seen more especially on the epicardium as well as on the pleura? pul- monales ; extravasations of greater or less extent also occur under the serous coats, in which case the extravasated blood is deposited in the form of hemorrhagic foci directly upon the sur- face of the heart and of the lungs. The heart is usually flaccid, its muscular fibres pale, and probably in prolonged cases also affected with fatty degeneration. Hemorrhages have been men- tioned as at tines occurring in the muscular tissue of the heart, likewise occasionally evidences of endocarditis valvularis. The tissue of the lungs is for the most part the seat of a bloody oedema, which is very frequently accompanied by hypostases in the form of catarrhal-croupous solidifications of the tissue of the lungs in their inferior and posterior portions, on both sides. Somewhat less frequent are the firmer hepatizations in other localities ; still, even extensive croupous pneumonia of one or the other lung has been observed in some cases (as a simple com- plicating process). Finally, in quite a number of cases the lungs contained more or less numerous hemorrhagic infarctions—in a few, even gangrenous foci of greater or less extent. The mucous 172 IMMERMANN.—SCURVY. membrane of the bronchi almost always exhibits extensive and numerous ecchymoses on an otherwise pale surface, and is usu- ally covered with abundant bloody mucus. The mucous mem- brane of the larynx is found in a similar condition, and, more- over, shows at times cedema in a very marked degree. There is also found at times in the abdominal cavity, although much less often than in the thoracic cavity, an hemorrhagic effusion accompanied by fibrinous secretions and deposits on the parietal and visceral serous surfaces, and numerous ecchymoses. On the mucous membrane of the stomach and small intestine are seen hemorrhagic spots and erosions, and at times more pro- found losses of substance, penetrating even to the muscular coat and showing villous edges infiltrated with blood (Opitz); blood, either clotted or in a half fluid state, is also frequently mingled with the contents of these portions of the bowels. The mucous membrane of the large intestine generally presents very marked lesions in those cases in which frequent bloody stools occurred during life(Samson-Himmelstiern, Cejka, Duchek). The mucous membrane appears swelled, is studded with very numerous hemorrhagic infiltrations, and is remarkably tender (which ex- plains why it bleeds so very easily); in some places a brownish- red, pulpy mass, at times quite considerable, may be wiped off from the surface of the mucous membrane, and the subjacent tis- sue is then found to be destroyed or quite filled with blood and softened. In other cases there is extensive follicular ulceration (Cejka), generally accompanied by an hemorrhagic infiltration of the edges of each small, roundish loss of substance. The contents of the large intestine are, like those of the stomach and small intestine, for the most part mingled with blood. The liver shows no pathological peculiarities other than hemorrhagic spots on its surface. The spleen is sometimes of normal size, much oftener, however, appreciably enlarged, and in this case contains more blood and is of diminished consistency. At times,, more- over, there exists in this organ wedge-shaped, hemorrhagic foci. In the pancreas, effusions of blood were on various occasions observed by Cejka. The kidneys seem often to have been found in a quite normal condition, even where albuminuria had existed during life (Opitz, Duchek); at other times, however, in cases POST-MORTEM APPEARANCES. 173 where the urine during life had contained large quantities of albumen, the evidences were found of a commencing or even of a well-developed parenchymatous degeneration of these organs (Cejka, Krebel); finally, in a few protracted cases even atrophy of the kidneys was observed (Opitz). Hemorrhagic spots were sometimes observed on the capsule of the kidneys ; infarctions too, of various size, have been seen in the cortical substance, less often in the deeper tissues. The mucous membrane of the pelvis of the kidney, of the ureters, and of the bladder, was often the seat of ecchymoses as well as of erosions, the contents of the urinary passages being in such cases for the most part tinged with blood. In the general description of the disease we mentioned very briefly the anatomical changes which ma}r occur in scurvy within the skull or in the organs of sight. Finally, in a disease like scurvy, which manifests itself by such prominent hemorrhagic symptoms, the condition of the blood-vessels, especially the capillaries, as well as that of the blood itself, deserves special consideration. But, strange to say, up to the present time no descriptions of aivv value in regard to the condition of the walls of the capillary vessels are to be found in the literature of scurvy—a fact which of itself would justify the conclusion that at least no positive anatomical changes of a very marked character are uniformly present in these vessels. This presumption, too, is in harmony with the result of the examina- tions of Lasegue and Legroux, who during the epidemic occasioned by the siege of Paris (1871), examined carefully the condition of the capillaries on the bodies of seven patients who had died of scurvy, and could discover nothing abnormal there, beyond very scattered fatty granulations. Now, in regard to the condition of the blood, this important question too, like that respecting the state of the capillary walls, has up to the present time given rise much more to theoretical speculation than to exact observa- tion and examination. We must not, however, be surprised at the small number of analyses of the blood that have been made in this disease ; we must remember that in recent times it is only seldom that an opportunity has been offered to take blood from scurvy patients in sufficient quantity and sufficiently pure to serve for examination; and we must also not forget that any 174 IMMERMANN. —SCURVY. direct attempt to take blood in this disease is attended with danger. Our knowledge of the condition of the blood of scurvy patients is, therefore, limited principally to the very rough results offered by an inspection of the blood of the cadaver in fatal cases, and to the results of a small number of microscopic and chemical analyses made only with partial accuracy on blood taken by the lancet or by cups during life. Autopsies showed that, where the disease had lasted but a short time, the blood found in the cavities of the heart and of the larger vessels was, as a rule, of dark color ; moreover, that it was sometimes fluid or only partially clotted, and some- times firmly coagulated; while, on the other hand, where the duration of the disease had been longer, the blood was rather of a lighter color and in a more fluid state, without, however, an entire absence of firm coagulations of fibrine even in such cases. These results by no means justify the conclusion that these alterations of the blood are in any sense specific, since precisely the same properties are discovered in the blood of the cadaver in innumerable cases of those who have suffered with quite different severe diseases of shorter or of longer duration. Nor has the matter been made really clearer as yet by the results of microscopic and chemical analysis ; and absolutely nothing characteristic, hardly even anything con- stant or positive, can be gleaned from the statements of those investigators who have formerly or even quite recently de- voted themselves to this subject. Now, in regard to the red blood-corpuscles, the examinations bearing upon this subject showed in the first place no anomaly in the form, that is, no shrinking of the blood-disks, as had been formerly assumed on no other ground than that of certain theoretical ideas (of an increase in the amount of salt contained in the blood of scurvy patients, and of a loss of water from the corpuscles occasioned by this) (J. Vogel). In regard to the aggregate number of the red blood-corpuscles, the statements of different authors vary, since some (Opitz) report that they have found the blood still very rich in these bodies in severe forms of scurvy; while others (Becquerel and Rodier, Chalvet), on the contrary, report that they have found a noticeable diminution in the nura- POST-MORTEM APPEARANCES. 175 her of the same in the advanced stages of the disease. Just as various, too, are the statements in regard to the amount of iron contained in the blood, which Opitz and Schneider report to be somewhat increased, Duchek to be about normal or slightly diminished, while Becquerel and Rodier, as well as Chalvet, report it to be (corresponding with the numerical decrease of red corpuscles seen by them) considerably decreased. According to Chalvet, too, the amount of potassa contained in the blood decreases in a degree corresponding to the diminution in number of the red corpuscles, a statement which has nothing surprising in it under the presupposition of oligocythsemia rubra, since potassa, like iron, is a preponderating element of the red blood- corpuscles only, while under normal conditions it exists in only very minute quantity in the plasma. Garrod, too, thought that he found the blood of a scurvy patient lacking in potassa, in an analysis which he formerly made (unfortunately, in a very imperfect manner), and by the aid of this untrustworthy result sought to give a further positive ground for his theory in regard to the nature and pathogenesis of the disease—a theory to which we have already alluded in the Etiology, and which is in other respects most worthy of attention. But, without further con- sideration, it must be clear to every one that quite as little use- ful advance would be made towards the theoretical comprehen- sion of scurvy by the simple proof of a lessening of the potassa, as of the iron, contained in the blood considered as a whole, since both these changes (the diminution, of iron as well as that of potassa) must be supposed to have taken place in every other oligocythsemia rubra. Now, as these changes undoubtedly take place in the various forms of anaemia, and still more in chlorosis (compare the chapter treating of this in volume XVI.), it is impossible to consider them as really pathognomonic character- istics of the blood of scurvy jmtients, or to attempt to explain the disease in this way. For the purpose of testing Garrod's theory that the diminution of the amount of potassa is the true and exclusive cause of the constitutional scorbutic affection, it would be far more important and convincing to obtain compara- the estimates of the amount of potassa contained in equal vol- umes of scorbutic and non-scorbutic red corpuscles, and to 176 IMMERMANN.—SCURVY. these might further be added analogous estimates of the amount of potassa contained in other tissues specially rich in potassa (particularly the striated and non-striated muscles). Examina- tions of this sort have not, at least to our knowledge, been as yet undertaken by any one ; we cannot, therefore, here make reference to any such.—In regard to the behavior of the white blood-corpuscles, recent statements (Laboulbene) indicate a con- siderable increase in the number of these bodies in pronounced cases of the disease ; in these reports, however, there is wanting anything to prove that the leucocytosis apparent to the micro- scope was also really absolute in the cases referred to, and the supposition is certainly allowable that the increase in number of the colorless corpuscles formed only an apparent departure from the normal, caused by the decrease in number of the red cor- puscles. But even supposing that absolute leucocytosis of the blood regularly existed in scurvy, the proof of this would still offer nothing pathognomonic, since it is well known that this departure from the normal has been of late observed in processes of disease most widely differing in character. Formerly specu- lation turned with very marked preference to the fibrine of the blood, and a decrease in this element was supposed to be the most important, perhaps the only change in the blood of scurvy patients by which especially the hemorrhagic diathesis was to be explained. When careful examinations, however, were really made, they did not by any means regularly prove a decrease of the fibrine; more often it was found to be present in normal quantity, and a few of the earlier as well as more recent analyses have shown even an increase in its amount. Thus, for instance, Becquerel and Rodier, in five scurvy patients examined by them, found the amount of fibrine to vary between 2.2 per cent, and 4.1 per cent.; Opitz and Schneider found it in one case to be 3.1 percent.; finally, Chalvet, as well as Lasegue and Legroux, found the quantity of fibrine to be about twice as great as it should be in a healthy individual, say 2.0 per cent. From these numerical data we may at least gather so much as this—viz., that the scor- butic manifestations cannot be attributed to a " hypinotic condi- tion" of the blood, and that theories grounded upon this sup- posed quality find no support in chemistry. ANALYSIS OF THE SYMPTOMS. 177 Andral and Gavarret, Becquerel and Rodier, Favre, Schnei- der, and some others, state that the amount of albumen con- tained in the blood is diminished; while Chalvet, on the other hand, maintains that it is increased. Authorities also disagree in regard to the salts of the serum of the blood, some holding that there is an increase in the alkalinity of this fluid, others that there is an increase in the amount of chloride of sodium, both of which conditions are held to be the cause of the scorbutic manifestations. For example, while Becquerel and Rodier in particular, as well as Denis and others before them, thought that they had found, in their examinations, an increase in the salts of the blood, especially of the chloride of sodium, to double the normal amount, and attributed to this excess the assumed diminished coagulability of the blood of scurvy patients, Schnei- der and Opitz were able by their analyses to prove the contrary, viz., a diminution in the amount of salts.—Now, if we take a general survey of the total results of the analyses made of the blood of scurvy patients up to this time, we can hardly avoid a feeling of dissatisfaction. From the various and contradictory statements of different authors we obtain but one, and that a decidedly negative result—namely, that the condition of the blood of scurvy patients, so far as we understand it at the pres- ent time, shows no peculiarities which might not occur as well in other pathological processes. Special Symptomatology. Analysis of the Symptoms of the Disease and of the Anatomi- cal Changes. In this section we will endeavor to illustrate, by a few explan- atory remarks, the account of the more important clinical and anatomical data bearing on scurvy, that has been given in the two preceding sections of this chapter. In this way we shall perhaps succeed in attaining a more exact theoretical com- prehension of the affection. Since in the majority of cases the characteristic clinical pic- VOL. XVII.—12 178 IMMERMANN.—SCURVY. ture of scurvy is ushered in by the development of a peculiar cachexia, and since this disturbance, which affects the subjective as well as the objective condition of the entire organism, per- sistently maintains a very conspicuous place among the various local scorbutic phenomena throughout the whole course of the disease, it seems necessary to give it the first place in the special consideration of the symptomatology as well as in the general clinical picture. It really looks in most cases as if all the other local manifestations of scurvy were developed from the already existing or primordial cachexia, and especially as if the facility with which the subsequent local processes are evolved in different parts of the body, as well as the intensity of these local processes, stood in a direct ratio to the severity of that general pathological condition! The cachexia of scurvy resembles in many respects that of anamia, particularly in the loss of power in the voluntary muscles, but also in the diminished force of the heart's action, and in the prostration of most of the vegetative functions of the body. The following symptoms may, however, be considered as more especially characteristic of the former, because they are at least not so constant and so marked in simple anaemia, even when it is excessive : rheumatic pains in the muscles—which are almost alwaj^s present even in the initial period, and which later often attain an excessive degree—and the usually excessive psy- chical depression, which is also one of the earliest symptoms of the change in the general condition in scurvy, and which, as we have already remarked, cannot be ascribed entirely to the often unfavorable surroundings of the patients. It is, moreover, worthy of remark, that the bodil}7" languor of scorbutic patients very often reaches an unusual degree of intensity even before the occurrence of local symptoms, and that it makes its appear- ance in general at an earlier period, and with more intensity, in scurvy than in the idiopathic or essential forms of simple anaemia. In a case of fully developed scurvy, the prostration is excessive, and can only be compared according to its intensity with the weakness and exhaustion that are observed in the acute anaemia following great loss of blood, or in the more severe forms of symp- tomatic anaemia accompanying fever, carcinoma, etc., or perhaps ANALYSIS OF THE SYMPTOMS. 179 in progressive pernicious anaemia. At the same time, however, the pallor of the visible parts, especially the mucous surfaces, is far from reaching that degree of intensity in scurvy which we are accustomed to find in simple severe oligocythaemia (or oligo- chromsemia); it is often even entirely absent when the disease has lasted but a short time, although a very marked disturbance of the general health may already exist and the patients per- haps already feel exceedingly wretched and feeble. Further, the change in the color of those parts that in health are vividly injected (the cheeks, lips, etc.), is especially distinct in the early periods of scurvy, but the parts become livid (cyanotic) rather than pale (anaemic). The tinge of the affected parts resembles more the dull bluish-red observed in patients whose blood con- tains sufficient colored elements, but in whom haematosis (decar- bonization) is incomplete in consequence of weakened action of the heart or of some other derangement of the circulation. Direct observations, moreover, seem to show that the blood of scorbutic patients in the earlier stages of the disease is not paler, but is rather of the normal color or even darker than normal blood; that consequently neither the number of the red corpuscles nor the amount of coloring matter contained in them has undergone any positive decrease (Schneider and Opitz); on the other hand, they prove that the circulation is affected and rendered slower at a very early period, as a result of actual adynamia of the heart. Hence, we are finally compelled to assume as necessary that the weakness of the heart, the muscular debility, and the- other manifestatiqns of the scorbutic cachexia, probably owe their origin to something else than an ordinary oligocytlmmiei. When, however, the disease is of long standing, the patient really becomes pale and anaemic to a degree dependent on the duration and severity of the attack, and particularly on the number and copiousness of the hemorrhages, the height of the fever, etc. In such cases a true anaemia is actually superadded to the scurvy as a complication or a sequel. Moreover, theo- retical considerations, which we will discuss more fully farther on, lead us to believe that, as the scorbutic cachexia increases in intensity, the reproduction of the red blood-corpuscles is gradually more and more interfered with, and that in the later ISO IMMERMANN. —SCURVY. stages of the disease an oligocythaemia is developed, which is not entirely consequent upon loss of blood, fever, etc., but is due to an actual interference with the development of the blood- tissue. While -asserting, however, this well-grounded opinion, that oligocythaemia occurs as an accidental change in the con- stitution of the blood, in the later stages of many severe cases of scurvy, we do not mean to insist less on the above-mentioned, and, as we think, equally well-grounded opinion, that the ca- chexia of scurvy is in itself and originally not an oligocythaemia (or oligochronnemia), nor an anaemia at all, but a special and independent constitutional affection. In addition to the pecu- liarities (rheumatic pains, psychical depression) already spoken of, we may, therefore, in accordance with the details given above, mention explicitly as a prominent characteristic of this patholo- gical species, a very severe functional derangement of the motor apparatus (the heart and the voluntary muscles), which must not be ascribed, as in anaemia, to a want of haemoglobine in the blood. As the cachexia of scurvy progresses, however, it is characterized, as a special form of constitutional disorder, par- ticularly by its local developments, which are peculiar in their nature, and are not met with in the same form in any other general disorder. Let us now briefly consider what the clinical picture and the anatomical lesions have taught us in regard to each of these local processes: as the scorbutic affection of the gums is the most frequent, and generally also the earliest ■ local symptom of scurvy, we will consider it first, and study more closely its nature and mode of origin. The histological changes in, and clinical appearances of the gums, even in the slighter forms of the affection, show that we have to deal with a decidedly inflammatory process, which begins with hyper- aemia and extravasation of the fluid elements of the blood, and leads to redness and painful swelling of the parts affected. The peculiarities which distinguish this stomatitis marginalis from other inflammations of the mucous membrane of the mouth, are the great tendency of the diseased mucosa to bleed upon pressure, touch, etc., and the fact that the affected part is not only hyperaemic and cedematous, but is also at the same time hemorrhagically infiltrated. The question whether ANALYSIS OF THE SYMPTOMS. 181 this extravasation of red blood-corpuscles into the tissue of the mucous membrane owes its origin, like the traumatic bleed- ing of the gums, to a rhexis of the capillaries, or, in addition to this, also to a simple diapedesis through the uninjured walls of the capillaries, must remain in abeyance, since this special point, which is without any great importance for the under- standing of the process, has not yet been cleared up. In general, however, we may deduce from the symptoms which exist the positive conclusion that the character of scorbutic sto- matitis is hemorrhagic, which indicates a diseased condition (abnormal fragility, combined perhaps with abnormal permea- bility) of the capillaries. It is true that in the more severe cases of scurvy the inflam- mation of the gums not unfrequently takes on a diphtheritic character or leads to diffuse ulceration of the affected mucous surface, but these exacerbations of the inflammatory process are not specially characteristic of scorbutus. It is well known that similar destructive processes are by no means rare in connection with intense inflammations of the mucous membrane of the mouth of entirely different origin (we may refer, for instance, to the more severe forms of stomatitis mercurialis). It would be just as incorrect to attribute exceptional importance to the hyperplasia of the connective tissue, which sometimes gradually takes place in the inflamed gums, and subsequently leads to permanent thickening and induration of the same, since it is likewise a well-known fact that a new formation of connective tissue very frequently appears as a late link in the chain of the elementary processes of inflammation when this has continued for a long time and is mild in form. It only remains for us, therefore, to consider briefly two questions in regard to the scor- butic affection of the gums—two questions which are, however, from their nature, of great importance. These relate, 1st, to the reason why this particular part of the body is so frequently and so eeirly affected; and 2d, to the connection between the hemorrliage and the inflammation in this peculiar pathological process. In regard to the first point, the other local symptoms in scurvy demonstrate sufficiently that neither the predisposition to hemorrhage nor that to inflammation is limited in this disease 182 IMMERMANN.—SCURVY. to the gums, but that, on the contrary, all possible parts and tissues participate in it. Further, a number of isolated observa- tions prove not only that the affection of the gums is not always the first local manifestation of the disease, but also that it may even be absent during the entire course of the disease. Finally, these observations teach in particular that the anomalous pri- mary local manifestations of scurvy occur especially on such parts of the body as have been in some way (mechanically, chemically, etc.) injured, and that, on the other hand, the development of the affection of the gums seems to be depen- dent upon the existence of teeth in the jaws, and therefore upon the act of chewing. All these circumstances taken to- gether render it at least very probable that the inflammatory and hemorrhagic affection of the gums occurs usually so early and so consteintly in scurvy simply because they are, con- sidering the tenderness of their histological structure, exposed to such various and severe mechanical, chemical, and thermic irritations (in seizing and masticating hard alimentary sub- stances, in the ingestion of highly seasoned articles of food, hot drinks, etc.). In considering the second point (connection between the hemorrhage and the inflammation), we must recall first the later local manifestations of scurvy, which were described in the sec- tion on General Symptomatology. They prove that extravasa- tions occur with remarkable facility in scorbutic patients with- out connection with any previously existing inflammation, but as direct results of injury of any kind ; they occur then at the very point injured. This behavior allows us to conclude that there is an alteration in the walls of the capillaries, entirely independent of inflammation, and which may be loosely char- acterized as a diminution in their power of resistance. On the other hand, it is clear that the inflammatory hyperaemia, which causes dilatation of the capillaries, may, where the resist- ance of these is insufficient, lead to a direct extravasation of blood by rupture and by diapedesis, precisely in the same way that this is brought about by any lesion due to external causes. It is therefore allowable to regard the bleeding of the gums in scurvy, whether it be superficial or interstitial, as the effect of ANALYSTS OF THE SYMPTOMS. 1S3 the combined action of external irritants and of inflammatory hyperaemia, and to explain it by both these factors acting together. On the other hand, however, it cannot be denied that an inflammation is now and then primarily excited, or an already existing inflammatory process aggravated, by the occurrence of interstitial bleeding, the blood extravasated into the interstices of the tissue acting as an inflammatory irritant. Finally, we must also bear in mind that, vice versa, any inflammatory alter- ation in the tissue of vascular parts, quite independently of the accompanying hyperaemia, influences in a very direct man- ner the power of resistance of the capillary tract affected, and thus of itself predisposes to hemorrhages. We have intentionally devoted considerable space to the con- sideration of the scorbutic affection of the mouth, not only because it seems to us to be particularly important on account of its frequency and its early development, but also because it is, in our opinion, specially adapted to facilitate the compre- hension of the genesis of other scorbutic local affections. If we consider next the scorbutic processes in the outer skin, in the connective tissue, and in the muscles, which we have already described, we find that in them, too, the hemorrhagic nature of the disturbance is exquisitely marked. These affections of the skin, connective tissue, and muscles are at times purely hemorrhagic in character, /. e., hemorrhages often take place in these parts during the course of the disease, either sponta- neously or after slight injuries, although no other gross lesions, and particularly no signs of inflammation, are present. In this way are produced, for instance, simple petechiae, ecchymoses, and vibices of the skin, and also those hemorrhagic infiltrations of the subcutaneous connective tissue and of the muscles which are developed without inflammatory redness of the skin cover- ing the part, without fever and without much pain. At other times, however, the hemorrhages accompany and are symp- tomatic of inflammatory processes, ex. gr., in purpura papu- losa, pemphigus, and rupia scorbutica, and also in those foci in the connective tissue and muscles which are developed more acutely, with pain, redness of the skin, and fever. Finally, in still other cases the clinical symptoms seem to indicate that the 184 IMMERMANN.—SCURVY. hemorrhage is the primary process, to which the inflammation is secondary, being excited by the interstitial effusion of blood. In short it is, on the whole, easy to trace a pretty complete analogy between the pathological process in these parts and the scorbutic alterations of the gums—an analogy, moreover, which continues throughout the entire course and in the ter- minations of the morbid processes. For, in tlie skin, the con- nective tissue, and the muscles also, under favorable circum- stances, reabsorption of the extravasated blood and resolution of the inflammation can take place, and the process finally ter- minate in complete recovery in loco. Under unfavorable circum- stances, on the contrary, the inflammation may take on a more malignant character, and lead to destruction of the tissue, or finally, it may gradually terminate in hyperplasia of connective tissue and leave behind a permanent induration (callosity, cicatrice). The case is exactly the same with the affections of the bones and of the periosteum, which, however, are more rare, as well as with the affections of the joints, which sometimes occur in scurvy. The clinical manifestations during life, and more espe- cially the lesions found after death, prove beyond question, that in the scorbutic affections of these parts we have also to deal with hemorrhages, or relativel}T still oftener with inflammations of a hemorrhagic character. These alterations, in their further development, do not in general present, either clinically or ana- tomically, any peculiarities that are specially characteristic of scurvy. Like the local scorbutic affections, which have been already investigated, their terminations are for the most part the natural, and indeed, the necessary consequences of the morbid processes that have been set up, and of the abnormal conditions of nutrition in the parts affected, occasioned by these processes. For instance, no one would be surprised to find that a portion of bone situated under a periosteal extravasation or hemorrhagic exudation in a scorbutic patient has become necrosed, since under all circumstances this is the usual fate of bone when deprived of its nourishing periosteum. For the same reason, there is nothing in itself remarkable or peculiar to scurvy in the necrosis of the cartilage when it has been detached by hemorrhage from the bony epiphysis, or in the ulceration of the capsule of the joint, that is occasionally observed in intense scorbutic arthritis. ANALYSIS OF THE SYMPTOMS. 1S5 With regard to the scorbutic affections of other mucous membranes than that covering the gums, the episiaxis consti- tutes a simple hemorrhage, from the abnormally tender capilla- ries of the nasal mucous membrane, excited for the most part by the mechanical irritation of blowing the nose. The genesis of the haematuria and of the hemorrhages from the stomach and intestines is less clear. As a rule, however, they are noo pre- ceded by inflammation, but rather present anatomically the characteristics of simple hemorrhagic processes. The case is different with the hemorrhetges from the large intestine; here the post-mortem examination most frequently reveals, as the cause of the bleeding, a severe inflammatory alteration of the mucous membrane of a dysenteric (diphtheritic-ulcerative) char- acter. The etiological connection of this inflammation with the general scorbutic disorder is probably not the same in every indi- vidual case. In the first place, different authors (comp. Etiology) have of late years drawn attention to the frequent coexistence of epidemics of scurvy and dysentery, and insisted particularly on the increased predisposition of patients suffering from diar- rhoea to the development of scurvy. There can be, therefore, no doubt that the affection of the large intestine existed pre- viously to the development of the scurvy in many of the cases in question ; the latter only added to the clinical picture of dysentery certain symptoms specially peculiar to itself, in par- ticular the pronounced hemorrhagic character of the stools, and thus produced the so-called dysenteria scorbutica, or scorbutic modification of the dysenteric process. Secondly.— Scorbutic patients may subsequently become affected with dysentery by infection with dysenteric poison. Abundant opportunity for this is often presented in naval expeditions to the tropics, in besieged cities, etc. Here, too, we have to deal with a com- bination of two different processes, but in an inverted order to the above ; and a special clinical type, namely, the hemorrhagic, is impressed on the dysentery by the already existing scorbutic disorder. TJiirdly.—Even without previous or subsequent infec- tion with the specific poison of dysentery, it seems that a severe hemorrhagic ulcerative process may sometimes be set up in the 186 IMMERMANN.—SCURVY. mucous membrane of the large intestine in scurvy (Duchek). This process, which is usually exceedingly deleterious in its action, then constitutes an actual localization of the general dis- ease, and corresponds perfectly in its pathological type with the more severe form of affection of the gums observed in so many scorbutic patients. Whether it is the mechanical injury oc- casioned by hard faecal masses, or the more chemical irritation of the mucous membrane by undigested and decomposing matters contained in the intestine, or some other noxious influence that constitutes the immediate exciting cause of this local scorbutic affection, we are for the present unable to state. It is, indeed, most probable that the direct exciting cause is not the same in every case. Duchek, although he concurs in general with the opinion advanced by G. v. Samson-Himmelstiern and Cejka, that this affection of the large intestine is in the majority of cases a complication, nevertheless believes that it is also at times merely a localization, and not an independent complication of the scurvy. He repeatedly saw the affection set in in scorbutic patients in the hospital, after the disease had existed for a long time, and terminate fatally by causing frequent intestinal hemorrhages. In these cases there was no reason to suspect a dysenteric infection. He believes that an hemorrhagic infiltration of the mucous membrane of the large intestine, which accompanied the surface bleeding, was probably the cause of the ulcerative destruction. The sanguinolent effusions into the pleura and the pericar- dium, as well as the much less frequent effusions into the peritoneal cavity, seem to be almost always the product of an exudative inflammation of these serous membranes, which is accompanied by extravasation. As evidences of the inflam- matory character of the process, we may adduce the anatomical changes in the serous membrane itself, the nature of the col- lected fluid, which does not usually consist of pure blood, and also the clinical course during life, which is, as a rule, febrile (comp. Description of the Disease). The terms "pericarditis or pleuritis exsudatoria sanguinolenta, and pericarditis or pleuri- tis scorbutica," seem, therefore, in general appropriate for these localizations of scurvy. The question whether cases of pure haemotliorax or haemopericardium do not also sometimes occur, in which there is simple hemorrhage without inflammation, must ANALYSIS OF THE SYMPTOMS. 187 fcr the present be left unanswered, since we are unable to find anatomical proofs of this in the literature of the disease. With regard to the mode of origin of these hemorrhagic exudations, some authors hold that the bleeding is the primary pathological process, while the inflammation is consecutive to and directly caused by the hemorrhage (Samson-Himmelstiern, Seidlitz, Duchek, and others). Although we do not by any means wish to deny that the extravasation of blood into the serous cavity may, at times, actually excite inflammation of its walls, and that the extravasated blood itself may act as the exciting cause of the inflammation, nevertheless the other theory does not seem to us to offer a less plausible explanation of the scorbutic affections in question. This theory is, that the hemorrhage is only the con- sequence of a pre-existing inflammatory hyperaemia, and of the increased fragility of the capillaries occasioned by the inflamma- tion. AVe should unquestionably give this latter theory the preference in the majority of the cases in which the extravasa- tion takes place gradually, and more especially in those in which the exudation contains only a smaller quantity of blood. In many of the acute cases, on the other hand, in which, as Krebel states, a copious effusion can often be found in the pleura or in the pericardium, after the expiration of only a few hours, and in which, moreover, the subsequent autopsy shows that the fluid is almost pure blood, the assumption of a primary abundant hemorrhage with consecutive inflammation would probably be more correct. As yet we have no positive knowledge of the exciting causes of pleuritis and pericarditis exsudativa sangui- nolenta, or of the primary hemorrhages which lead to their development in some cases. The assertions of Seidlitz, Krebel, and others, that cold, damp weather and the existence of the so-called "rheumatic constitution" are particularly favorably to the development of these processes in scorbutic patients, would, even if we were to concede them to be correct, apply rather to the case of primary inflammation with subsequent hemorrhage than to that of initial hemorrhage with consecutive inflammation. The signification of these etiological factors must not, however, be estimated too highly. Even supposing that we were willing to admit that man}' of the cases of hemorrhagic pleuritis, which 188 IMMERMANN.—SCURVY. have been observed in scorbutic patients, were rather mere acci- dental complications of the pre-existing disease, due to subse- quently "catching cold," or to the influence of a "genius epi- demicus rheumaticus," we should scarcely attempt to explain in a similar manner the much more frequently observed san- guinolent inflammations of the pericardium. For we know from experience that a primary "rheumatic affection" of this latter serous membrane in healthy persons is extremely rare. In attempting, therefore, to explain the peculiar fact that hemor- rhagic inflammations of the serous membranes, and especially of the pericardium, are relatively frequent in the course of scurvy, and are often, as it would seem, developed spontaneously, we are compelled to take refuge in the assumption that in scorbutic patients the serous membranes, and especially the pericardium, like many of the other tissues, are more strongly predisposed to inflammation than the same parts in healthy subjects, and that it only requires the stimulus of very trifling and consequently easily overlooked or perhaps unknown causes, to light up actual inflammation in these membranes. All the scorbutic affections of the eye, which were briefly studied in the general description of the disease, also belong in the category of hemorrhagic or hemorrhagic - inflammatory processes. They are consequently entirely conformable in character to the localizations of scurvy in other parts and organs, which we have just discussed. The fact that the external covering of the eyeball, namely, the conjunc- tiva, is most frequently the seat of the extravasation and inflam- mation, may unquestionably be satisfactorily explained by the exposed situation of this membrane. We have finally to investigate briefly a few pathological phenomena which were mentioned at the close of the section on general symptomatology. In their anatomical and clinical char- acteristics these do not correspond exactly with the phenomena that we have thus far been studying, but they are nevertheless worthy of attention because of their frequent, and in part, per- haps, regular connection with the disease. One of the symptoms of this sort, which is frequently but by no means regularly met with, is the enlargement of the spleen. The signification of this symptom in scurvy can as yet be only very indefinitely and ANALYSIS OF THE SYMPTOMS. 189 indeed negatively determined. When it is developed in the course of the disease—apart from those cases where it arises from certain complications, especially malarious infection—it seems to depend not so much on the mere fact of the existence of the scurvy, as more particularly on the severity and intensity of the affection. At the same time, however, there have been a good many exceptional cases where, although the disease is very severe and extensive, the spleen remained small and was found at the autopsy to be of normal size. In the fatal cases, in which an enlargement of the spleen was developed during the course of the disease, and where the post-mortem examination rendered it possible to ascertain exactly the nature of the anatomical altera tions, these were found to consist in hyperaemia of the organ, with pulpy softening of its tissue. The scorbutic enlargement of the spleen may consequently be classed with the acute enlarge- ments of the spleen that are apt to occur in the course of typhoid fever, recent intermittent fever, acute miliary tu- berculosis, and other febrile-infective processes. It does not, however, seem to us by any means allowable to assume on this account some toxic, infective principle as the cause of these and other cases of scurvy. The anatomical lesion in question is certainly worthy of notice, but it cannot serve in any way to explain the nature and pathogenesis of the disease. 2. The albu- minuria also, as we have already mentioned, is for the most part only found in severe cases of scurvy. It frequently occurs as a pathological symptom in cases in which no anatomical lesion of the kidneys can subsequently be demonstrated. We believe ourselves justified in assuming that the form of albuminuria, which is not due to a complicating degeneration of the kidneys, really deserves the name of scorbutic albuminuria, and is depen- dent upon delicate vascular changes in the kidneys. We are still unable to demonstrate these changes anatomically, but they are nevertheless sufficient to permit a filtration of the albumen of the blood from the vessels into the urinary canals. We be- lieve, therefore, that we have to deal here with the same nutri- tive or functional alteration of the walls of the blood-vessels, which must be assumed as the cause of the general hemorrhagic diathesis in scurvy. When this alteration is more highly devel- 190 IMMERMANN.—SCURVY'. oped in the uropoetic apparatus, it gives rise to the phenomenon of haematuria. Finally, in cases of albuminuria, where marked degeneration of the kidneys was found after death, the genesis of the former of course depends directly on the existence of the latter. 3. While we were describing the clinical picture of the disease, we mentioned further some other interesting character- istics of the urine, which Duchek discovered during his exami- nations of this excretion in the various stages of the disease, and which he asserts to be regularly present. The decrease in the quantity of the urine and of most of its solid constituents, as long as the disease is growing in intensity, and the converse increase of the quantity and of the solid matters in the period of defervescence, can both be pretty easily brought into genetic con- nection with the changes which the-heart's action, and probably also those which the entire processes of nutrition, undergo in the different phases of scurvy. As with the increase of the scor- butic cachexia the action of the heart becomes weaker, and the nutritive changes, in consequence of the enfeebled circulation, become more and more sluggish, the urine in an equal ratio becomes less abundant and the total amount of its solid elements smaller. Inversely the re-establishment of a more active circula- tion, and the increased activity of all the organic processes which accompany convalescence, must be attended by an increase in the quantity of the urine and in the amount of its solid contents. It is a noticeable fact, however, that in the cases examined by Duchek the phosphoric acid, and particularly the potassa, did not participate in the quantitative decrease of the other solid elements of the urine in the first period of the disease.. On the contrary, at the height of the disease these constituents appeared to be relatively, and, in three of the six cases examined, even absolutely increased in quantity. If we assume it as granted that this excess of potash and phosphoric acid will in future be discovered with a certain regularity in scorbutic patients, and will be found to constitute a tolerably constant attribute of the disease, we may explain it in a variety of ways. In the first place, Duchek himself believes that the relatively abundant excretion of potassa in his patients, during the entire course of the disease, might very well have been occasioned by the use of food rich in ANALYSIS OF THE SYMPTOMS. 191 potassa (vegetables), with which they were generously supplied, and indeed that it was doubtless, in part at least, due to this. If this view be correct, however, the abundant excretion of potassa in the urine would then in our opinion be an indirect proof that relatively little of the potassa taken into the system and absorbed by the circulating fluid really remained behind in the body of the patient and was employed for organic purposes. Inverse^, the not only relative but actual decrease in the excre- tion of potassa during convalescence, which was also demon- strated by Duchek, might be explained by the assumption that conditions which had meanwhile set in were more favorable to the assimilation of the potassa in the food. It is possible, how- ever, as Duchek also suggested, that the absence of a diminution in the excretion of potassa and phosphoric acid during the earli- est part of the disease might be due to a comparatively excessive disintegration of those tissues of the body which are rich in potassa and in phosphoric acid, such as particularly the red blood-corpuscles and the muscular fibres. It would conse- quently be an indication that, in spite of the interference with the nutritive changes in general, the waste of certain tissues that are rich in potassa and phosphoric acid still continues relatively great, if indeed it is not absolutely increased, as happened in three of the cases examined. Finally, an absolute increase in the amount of potassa excreted has recently been demonstrated to occur during the existence of fever as an actual symptom of the febrile process (Salkowsky, Senator); and it seems to us, inasmuch as fever is a very common occurrence in severe cases of scurvy, that it is at least possible, if not probable, that the observations of Duchek were made on patients who were at the time suffering with fever, and that the increased excretion of potassa may have been in part a simple febrile phenomenon. It is evident, then, that the facts adduced by Duchek are capable of very various explanations, and for this reason they do not for the present afford us any secure standpoint for the develop- ment of a definite theory of scurvy. Nor are we disposed to agree with Duchek in the opinion that they are calculated to remove an objection to Garrod's hypothesis, which suggests a diminution in the quantity of potassa taken into the system as be- 192 IMMERMANN.—SCURVY. ing the cause of the scurvy, and that they furnish at least a nega- tive proof for it. So long as exact comparative observations are entirely wanting in regard to the quantities of potassa taken into the system and excreted by scorbutic patients who are free from fever, it will not be permissible to conclude, from the non- appearance of a diminution of the excretion, that the potassa goes through its permutations in the system, in all respects in a regular manner. It will be much better to leave the question in regard to the amount of potassa assimilated and excreted during this disease, for the present entirely open, and to await the result of more decisive examinations. Finally, we return once more to the conditions of tempera- ture in scorbutic patients, in order to call attention to the fact that the thermometric curve does not by any means conform to a con- stant rule in the individual cases. It may be confidently stated, however, on the basis of actual observations, that scurvy is in itself not a febrile disease, but that, on the contrary, fever is only an accidental and intercurrent, although an exceedingly common symptom. It occurs particularly in the more severe cases as a consequence of existing inflammatory localizations of the disease, and then continues during a shorter or longer period. In such cases, therefore, it is proper to speak of a "fever of individuals suffering with scurvy," but not of a '' scorbutic fever.'' Nature and Pathogenesis of the Disease. At the beginning of this chapter, we defined scurvy to be a general derangement of nutrition, in which, in addition to a more or less severe, and at the same time peculiarly modified cachexia, hemorrhagic and hemorrhagic-inflammatory localiza- tions occur in various organs and tissues. The analysis of the symptoms of the disease which has just been terminated, has, we think, demonstrated by details the correctness of the general definition previously given, and has particularly furnished proofs that the characteristic local symptoms of the disease can all be considered as the results of a definite, general, morbid condition; or, in other words, of a constitutional anomaly of the body. NATURE AND PATHOGENESIS. 193 The constitutional nature of the disease is still more clearly demonstrated by the pre-existence of the scorbutic cachexia, which, as a rule, at least precedes by some space of time the local eruptions. When considered in connection with this initial affection of the entire body, the later local phenomena appear for the most part only as further partial perturbations of a de- rangement of the organic processes, which involves the entire sys- tem. The clinical form of these partial lesions is, however, as we have shown, double : either the inflammatory diathesis goes hand in hand with the hemorrhagic diathesis, or, along with an unusual tendency to extravasation of blood per rhexin, and prob- ably also per diapedesin, there exists an abnormal vulnerability of most of the tissues, in consequence of which inflammation is very readily excited in them by slight injuries of any kind, or even, as it would seem, appears spontaneously. The character of the inflammations thus produced is, however, for the most part, also hemorrhagic ; either the inflammatory hyperaemia leads to extravasation from the brittle or abnormally permeable capilla- ries, or, on the other hand, the extravasation acts as an inflam- matory irritant to the tissues with which it comes in contact. Everything considered, therefore, scurvy is a hemorrhagic, con- stitutional disease, in which, to distinguish it from other forms of the hemorrhagic diathesis, the cachectic nature is strongly marked, and at the same time the tendency to inflammatory lesions of the tissues is veiy great. The etiolog}7" of the disease shows, moreover, that it is not a congenital constitutional anomaly, like haemophilia; nor is it, like the latter, transmissible from father to son, or, in the majority of cases, hereditary ; on the contrary, the disease is first acquired after birth, under the influence of certain anti- hygienic conditions to which, as a rule, not single individuals alone, but whole bodies of men at once are subjected ; hence, it commonly appears in the form of extensive or circumscribed epidemics, seldom in isolated cases. It would be incorrect, con- sequently, to seek for the essence of scurvy, like that of haemo- philia, in some vitium primae formationis. On the contrary, it is fair to assume that the anomalies in the vascular system devel- oped at a later period, and the diminution of the physiological VOL. XVII.—13 194 IMMERMANN. —SCURVY. resistance of the tissues to inflammations, both of which are observed in scorbutic patients, are the results of an alteration in the nutritive process, occasioned by the outward circumstances of existence of the individual. Hence, the answer to the ques- tion as to the pathogenesis of scurvy would essentially depend upon the discovery of the manner in which, under the influence of the causes discussed by us in the section on Etiology, the normal nutritive process may become so altered in the vessels and the tissues supplied by them, that hemorrhages readily occur and inflammations are easily developed. In the first place, we must here insist on one thing, viz., that as the etiology of the individual cases or epidemics of scurvy is notoriously not always exactly the same, so the pathogenesis cannot with any more reason be a priori considered to be the same for all cases. We must clearly understand that the insuf- ficient power of resistance and the permeability of the capillaries, as well as the vulnerability of the tissues, can, as we know by experience, not only be occasioned by very various injurious influences, but possibly, too, in very different ways by these various causes. Our theoretical speculations will unquestionably reach a plausible result more rapidly if we investigate, first, the possible mode of action of those pernicious agencies whose influence in exciting scurvy has been positively demonstrated in an empirical manner by numerous and exact observations, leav- ing the remaining agencies, known to be prejudicial, for subse- quent consideration. It was in this way, as we have already repeatedly stated, that Garrod proceeded, when he erected his so-called potass a-theory of the disease upon the basis of the thousandfold authenticated fact, that scurvy is developed with the greatest facility among persons who are deprived of a fresh vegetable alimentation (green vegetables, potatoes). Since those aliments, on the total absence of which from the food the scorbutic cachexia with its secondary local consequences most frequently depends, are specially rich in potassa, and contain, moreover, this alkali in a form particularly easy of assimilation (in combination with carbonic or some vege- table acid), Garrod further concludes that the scorbutic affection is due chiefly to an insufficient supply of potassa in the organ- NATURE AND PATHOGENESIS. 195 ism.—It cannot be denied that this theory is in several respects very seductive ; it not only seeks to do justice to the special physiological nutritive value of numerous articles of food, which contain otherwise very little nutritive matter, in the usual sense of these words, and the deprivation of which for this very reason is not in fact followed by ordinary marasmic anaemia, but it is also supported by weighty facts derived from the chemistry of the tissues. These facts prove that a deprivation of potassa is by no means a matter of indifference to the organism. For, little as is otherwise known in regard to the special physiological impor- tance of most of the inorganic nutritive substances, and in par- ticular of the potash combinations, these two facts are positively settled, viz., that potassa forms an integral constituent of all tis- sue-elements (cells), and that precisely some of the tissues which are physiologically of the greatest importance, such as the mus- cular fibres and the red blood-corpuscles, are especially rich in potassa. If we take these facts into consideration, it will certainly be easy to understand that an insufficient or inappropriate supply of potassa in the food would not presumably be without a patho- logical action on all the tissues of the body, and especially upon such as contain large quantities of potassa. At first the phys- iological function of the tissue, and its normal physiological resistance to causes of disease of every kind, will be impaired, and later on, the deprivation of potassa continuing, the phys- iological reproduction of the tissue-elements will probably be checked. It surely needs no further demonstration to show that both the disturbance in the subjective and objective general con- dition, and also many of the special peculiarities of the scorbutic cachexia—for instance, the very pronounced functional derange- ment of the heart and the voluntary muscles — the tendency, moreover, to inflammatory lesions of the tissues terminating frequently in ulceration, etc., and finally, also, the oligocythae- mia which gradually makes its appearance in the later stages of the disease, can readily be accommodated theoretically with this view. Referring now particularly to the hemorrhagic diathesis in scurvy, and to its possible connection with the insufficient supply of potassa to the organism, we may either assume a 196 IMMERMANN.—SCURVY'. t direct trophic impairment of the capillary walls, or what is more probable, an indirect impairment of their function and nutrition through the red blood-corpuscles. These latter being less rich in potassa, and thus weakened in constitution, are no longer able to accomplish the task of keeping the capillary walls in a state of functional and nutritive health. This is not, however, the place to lose ourselves in further conjectures. We must simply endeavor to deduce a really pathological cause from the pathogenetic influence which is in all probability furnished by insufficient supply of potassa to the organism, and which possibly also has a direct etiological action in very many cases of scurvy. It is evident that it is not the insufficient supply of potassa, nor the presence of this substance in too inconsiderable quantities in the cir- culating fluid, but the consequent want of potash in the tissues themselves, which must be regarded as the real mor- bid condition and as the cause of the perverse (functional, nutritive, and plastic) behavior of all the tissue-elements, includ- ing naturally the red blood-corpuscles, or the elements of the blood-tissue. Any series of experiments, therefore, which might be undertaken with the object of obtaining, on the basis of Garrod's hypothesis, an anatomical and chemical substratum for the understanding of scurvy, must aim at determining the com- parative quantities of potassa contained in the red blood-corpus- cles, the muscles, and other tissues in healthy persons, and in scorbutic patients. They must not, however, be limited entirely to analyses of the blood as a whole, since these would only fur- nish proof of the condition at a given moment of the general nutritive fluid, which constantly varies in the percentage of its component elements. Although no comparative investiga- tions of this sort have as yet been made, and Garrod's theory is on that account unfortunately still unprovided with a firm anatomical basis, it may nevertheless be profitable, with a view to the establishment of the possible mode of origin of scurvy, to devote a short space to the hypothesis that a want of potassa in the tissues, or a want of organic potassa {not of potassa cir- culating in the fluids), may bring on the scorbutic disorder. Evidently this latter theory affords a much more reliable basis NATURE AND PATHOGENESIS. 197 for a comprehension of the pathogenesis of individual cases of scurvy than the theory which only takes into account an insufficient supply of potassa to the organism, for it does not seek to explain how the want of organic potassa has been occa- sioned in the concrete cases. An insufficient supply of potassa in the food is one, but by no means the only possible way in which this absence of potassa-in the tissues can be produced. It will not be uninteresting, and is, indeed, necessary, to con- sider here briefly some of the other possible ways in which it can be produced ; in doing so we shall take the opportunity to recon- sider some of the empirical statements made under the head of Etiology. A want of potassa in the tissues can in the first place also be due to the fact that the potash combinations are supplied to the circulating fluid by the food in sufficient quantity, but in a form that is ill adapted for assimilation. In this case they are soon discharged from the body in the excretions, without having previously been appropriated by the tissues, and thus without having fulfilled their physiological purpose. In this connection the remark of Chalvet, a decided advocate of the potassa theory, is worthy of notice. He explains in this way the fact that green vegetables and potatoes are so much more valuable as anti-scorbu- tics than the dry leguminous vegetables and meat. He believes, moreover, that the deprivation of the first-named articles of food is the most pregnant cause of scurvy, simply because they con- tain potassa in the unstable, and, therefore, easily assimilable form of potash, and also in combination with the vegetable acids, while the same alkali exists in meat, dried leguminous vege- tables, and bread, in considerable quantities, it is true, but in the much more stable forms of chloride of potassium and phosphate of potassa. Garrod, too, relying on his often mentioned inves- tigations of the chemical constitution of various articles of food, pronounced decidedly in favor of taking the percentage of pot- ash in them as the measure of their antiscorbutic properties, and, as we mentioned on page 134, chose particularly the remarkably high figure of the carbonate of potassa in the potato as the point of departure in his theoretical speculations. In the second place, a deficiency of organic potassa may arise in spite 198 IMMERMANN.—SCURVY. of an abundant and appropriate supply of potassa in the food, when derangements of the digestion exist accompanied by diar- rhoea. The food which is taken into the stomach is, under such circumstances, prevented from entering the circulating fluid in sufficient quantities. The question whether the predisposition of dysenteric patients, and of persons suffering with diarrhoeal dyspepsia, to scurvy, as well as the development of the affection after the ingestion of decomposing articles of food and of foul water, may not be due to this circumstance, must for the present be left unanswered, although it must be borne in mind as a possibility. In the third place, the taking up of the circulating potassa by the tissue-elements must also undoubtedly be in- fluenced by all those weakening agencies which lessen the trophic energy of the cells, and diminish their capacity to appro- priate the potassa from the blood. As instances of these influ- ences, we may mention deprivation of fresh air and light, idle repose of the body, and excessive heat. We have already stated that these external pernicious influences are also counted among the causes of scurvy, and, with good reason, as it seems to us, always find a place in the etiology of this disease. In defence of the explanation of their mode of action, which we have just attempted to give, we will merely refer to that fundamental cellular principle, according to which the taking up of different substances from the blood into the living cell-body is a vital action of the latter (Virchow). It is therefore possible that even the most abundant supply of potassa from without may be useless, if, in consequence of great prostration of the patient and exhaustion of the nutritive energies of the tissues, the cells no longer possess the power to extract from the stream of nutritive matter which flows by them the substances neces- sary for their own regeneration. It certainly seems right to hold up all these possibilities to the view of the opponents of the potassa theory, who might otherwise with apparent reason base their opposition on the fact that scurvy has at times occur- red among persons supplied with food containing potassa in abundance, and has even persisted under these circumstances (for instance, the epidemic of Rastatt). These possibilities pre- sent the theory in a somewhat different light, namely, under the NATURE AND PATHOGENESIS. 199 form which we have just described, and which is decided]}' more appropriate for such cases as the above. It is sufficient simply to mention the facts, that the distance which the alimentary sitbstance containing potassa has to travel in passing from the mouth to the tissue-elements is considerable, that it is readily turned aside from the direct course, and finally, that even when it has safely arrived at the cells, it is not always necessarily absorbed into them. It is evident that the amount of potassa contained in the tis- sues must depend on the quantity consumed in, as well as on the quantity taken up by, the tissue-elements. Hence whenever, in consequence of unusual activity of the organic processes, a large quantity of potassa is temporarily discharged from the tissues into the circulating fluid, whence it is eliminated through the excretory canals, the demands of the body for a more abundant supply of potassa must of course be particularly great, and a non-compliance with these demands will probably easily give rise to morbid disturbances, and in particular to scurvy. It would be exceedingly interesting, and it is even important, to know, for instance, how the expenditure of potassa during severe bodily exertion compares with that during a state of repose, and further, how the amount consumed during a long continued sojourn in a damp, cold atmosphere would compare with that consumed during a sojourn of equal length in a temperate or warm and dry climate; since hardships and damp, cold weather have been so frequently asserted to be exceedingly active acces- sory causes of scurvy. As, however, no direct investigations of these points have as yet been made, it is for the present unfor- tunately impossible to test the soundness of the potassa theory in these respects. The decision of the question, whether or not that theory suffices to meet these etiological demands, must await the results of further research. Finally, we will also men- tion that the increased excretion of potassa during fever, demon- strated by Salkowsky,1 teaches us at least one important fact, viz., that the amount of potassa consumed under definite patho- logical conditions does not by any means conform to the amount ' Virchow's Archiv. Bd. LIII. 2. 3. 1871. 200 IMMERMANN.—SCURVY. of potassa supplied, but follows solely its own laws. Whether or not there are also physiological conditions which, in regard to the waste of the potassa of the tissues, are analogous to fever, is a question that is not answered by the investigations of this observer, since these, so far as they relate to healthy subjects, have been directed only to the influence of the food—that is, of the supply of potassa—upon the excretion of this substance. Although, however, the results of Salkowsky's investigations cannot as yet be made use of to determine theoretically the varying predisposition of healthy persons to scurvy under different conditions of existence, we may at least deduce from them the conclusion that there is an increased predisposition to scorbutic symptoms on the part of fever patients and of convalescents from febrile diseases. In fact, obser- vations at our disposal seem to prove that individuals who are enfeebled by some severe disease are more rapidly attacked by scurvy than those whose powers of resistance are in the normal physiological condition. Some exquisitely marked febrile affections, for instance, particularly intermittent fever, occasion in fact an unusually intense predisposition to scurvy. Duchek is inclined to ascribe the fre- quent occurrence of scurvy as a complication of malarial fever, which he has himself observed, to the extremely rapid destruction of the red blood-corpuscles (in other words, to the extensive disorganization of a tissue peculiarly rich in potassa) in intermittent fever. This destruction does not seem to be due entirely to the fever; it is, in part at least, the effect of the specific infection itself. In what precedes we have sought to secure for Garrod's po- tassa theory of the pathogenesis of scurvy all the domain which it is able, under whatever circumstances, by virtue of its own inherent plausibility, to hold in subjection. We have, moreover, endeavored particularly to show that a number of cases and epi- demics of scurvy, in the production of which a scarcity of food rich in potassa was notoriously not an active factor, can also, to some extent, be explained by this theory ; but we nevertheless do not wish to be understood as having in the least degree prejudged the question as to the possible modes of origin of these cases. For instance, we do not by any means wish the preceding deduc- tion to be understood to mean that, in our opinion, the syndrome of scurvy must of necessity be the result of a scarcity of potassa in the tissues in all those cases in which there is a high degree of probability, or even only a remote possibility, of the existence of this pathological alteration. We do not deny that the dis- ease might possibly in some, or, indeed, in very many of these COMPLICATIONS AND SEQUELAE. 201 cases, have originated from very different morbid factors. How far the casuistical domain of that theory actually extends, and whether it really possesses any such domain, are questions for answers to which we must look to future investigations. The direction which it is desirable for these investigations to take has been described above. Meanwhile, it will certainly be well in any case to bear in mind the possibility that the scorbutic symptoms may not always take their origin in the same derange- ment of the general nutrition, but that not on\y the pathogenesis and the etiology, but also the chemico-pathological substratum, may perhaps vary in individual cases. In view of the facts here discussed, the assumption may seem plausible that a want of the needful quantity of organic potassa may influence injuriously the integrity of the tissues and with it the health, and that the special form of the derangement of the health thus occasioned is in every case the scorbutic. On the other hand, however, there is nothing in them which offers the least contradiction to the hypothesis that precisely the same combination of symptoms, namel}r, a general cachexia, accompanied by hemorrhagic inflam- matory localizations in different tissues, might at another time be produced by trophic derangements of quite a different character, such, for instance, as those occasioned by mias- matic poisoning. It must always be remembered, that the disease known in pathology as " scurvy " for the present forms only a symptomatic unity, and that the name of the disease is strictly considered not much more than the conventional, short expression for a special collection of morbid symptoms. If we bear this in mind, we shall be able to restrain ourselves and others from premature and perhaps entirety hopeless attempts at unification on an etiological, pathogenetic, and chemico-path- ological basis. Complications and Sequela?. It has been already noted in the etiology that scurvy not infrequently attacks individuals who are already suffering from disease, and then itself plays the part of a complication of the pre-existing pathological process. We have also named at the 202 IMMERMANN.—SCURVY. appropriate place those affections, such as malarial diseases, dysentery, and syphilis, which show a peculiarly marked tend- ency, where the conditions are favorable for the development of scurvy, to become complicated with this disease. At other times the secondary scorbutic affection seems to be merely an accidental complication of the pre-existing fundamental disease, since the empirical proof of a more frequent coincidence of the two cannot be adduced. In this connection it is necessary to state briefly the fact that scurvy may occur as a complication during the course of the most diverse morbid processes. The modifications which this complication occasions in the clinical character of the pre-existing disease are almost always of an unfavorable nature. The derangement of the general health then almost invariably becomes more marked, and the signs of a pronounced cachexia usually appear very rapidly; but aside from these, the hemorrhages which now occur in loco affectus, as well as in other parts of the body, have their effect in aggra- vating the condition, and may even be the direct cause of a fatal issue of the primary disease. This is apt to be the case, for instance, when scurvy supervenes as a concomitant constitu- tional anomaly, in the course of dysentery, typhus, pneumonia, phthisis, and inflammations of the serous membranes, particularly pleuritis, and finally, when it complicates suppurating and granulating wounds, fractures, and inflammatory diseases of the joints. Observers have had opportunities on many different occasions to convince themselves of the increased malignity of all sorts of severe affections, both internal and surgical, in the contingency just described. On the other hand, convalescents from scurvy, and patients who are still suffering from the disease, are liable to be attacked by other diseases. In such cases we have, of course, to deal with complications or with sequelae of the scorbutic affection itself. These secondary affections, again, may be entirely acci- dental, having no demonstrable genetic connection with the exist- ing or antecedent scurvy ; in other cases, as some observa- tions at our command prove, a connection of this sort can be traced to a certain extent. With regard to the accidental com- plications and sequelae, which may be very diverse in their nature COMPLICATIONS AND SEQUELAE. 203 and cannot here be enumerated in detail, we may make the general statement that they run a much more severe course than under ordinary circumstances. The reason of this is to be found in the fact that they are developed, not in a healthy organism, but in one that is shattered and exhausted by the cachexia, which is either still in full force, or at least has not yet been entirely overcome. Naturally, those cases are relatively most unpropitious in which the scurvy itself is not yet eradi- cated, and the supervening complication is inherently severe in its nature. The case is more propitious when less serious affec- tions occur as accidental sequelae of a scurvy that has already run its course. In the true complications, independently of the great exhaustion of the patients, the hemorrhagic-inflammatory diathesis especially exerts a disturbing and dangerous influence on the regular course of the affection, while in the sequehe it is the anaemia that has been left behind by the antecedent scurvy, and constitutes in fact a secondary constitutional affec- tion, which is the principal cause of the diminished power of resistance on the part of those attacked. We must content our- selves with this brief mention of the principal traits in the clini- cal behavior of such accidental processes, since a closer inves- tigation of their details does not seem to us to be in place here. Among the complications of scurvy which are observed with relative frequency, and which consequently have perhaps a more direct connection with the scorbutic affection, we must mention, on the part of the respiratoiy apparatus, particularly croupous pneumonia. At least, it is not very unusual to find at the autopsies of persons who have died of scurvy, the anatomical signs of a more or less recent hepatization of extensive portions of the lungs. In other cases the subjective and objective chest- sjmiptoms during the lifetime of the patients indicate the acute development of a pneumonic process. The pneumonia of scor- butic patients runs, as a rule, a very severe—for the most part, indeed, a fatal course. The immediate cause of death is appar- ently, in most cases, the extreme insufficiency of the heart's action—a direct effect of the existing scurvy, which from the very beginning impresses on the supervening pulmonary affec- tion an adynamic character. Sometimes, too, at the height of 204 IMMERMANN.—SCURVY. the disease, before the fatal issue, mortification of the tissue of the lungs sets in with the characteristic signs of pulmonary gangrene (stinking, discolored sputa). In such cases the autopsy shows, in addition to the pneumonic infiltration, gangrenous foci of greater or less extent in the midst of the hepatized tis- sue. Hemorrhagic infarction is also a frequent complication of scurvy. The infarctions are usually multiple, and the anatomi- cal changes characteristic of them are often found in the lungs at the autopsy. The mode of production of these foci is, as a rule, the same in scurvy as under other circumstances—namely, by embolism ; the emboli are derived from thrombi which form in the right auricle, and particularly in the appendix auriculae, in consequence of the enfeebled circulation. The acute, ulcerating valvular endocarditis, which is some- times, but not often, found at the autopsies of scorbutic pa- tients, should probably be regarded as a merely accidental com- plication, occasioned perhaps by septic infection originating in scorbutic ulcers of the skin or wounds. In the majority of the cases of scurvy that terminate fatally, the valves have been found perfectly intact, although blowing murmurs over the heart are very frequently heard during life. Hemorrhagic peri- carditis* like the analogous form of pleuritis, and of the less frequent peritonitis, must be classed among the localizations of scurvy, since they belong with those lesions which, although they may occur exceptionally under other circumstances, are essentially characteristic of this disease, and are very commonly found at the autopsies of severe cases. We have also already had occasion to speak of the relation which the occasionally observed diphtheritic-ulcerative enteritis bears to the scurvy. We pointed out, in particular, that this process, which is almost always attended by violent symptoms, especially by frequent discharges of blood per anum, and rapidly leads to a fatal termi- nation, must at times, like hemorrhagic pericarditis, and other hemorrhagic forms of inflammation, be regarded as merely a localization of the existing general disease, while in other cases, on the contrary, it is an actual complication due to infection with dysenteric poison. On the part of the kidneys, we must mention the existence of COMPLICATIONS AND SEQUELAE. 205 parenchymatous degeneration in a considerable number of those cases of scurvy in which albuminuria existed during life (Cejka, Krebel). We have already expressly stated, however, that in quite as many of the cases, where albumen appeared in the urine, gross alterations in the kidneys were entirely absent. Finally, of the complications of scurvy which affect the nerv- ' ous apparatus, we must mention an anomaly of sight—namely, hemeralopia. The connection of this peculiar morbid phenom- enon with scurvy has been, both in former times and quite recently, the subject of active discussion. In the first place, it is a fact that hemeralopia and scurvy have been very frequently found coexisting in the same persons; usually the scurvy is developed first, the patients subsequently becoming hemeralopic. It is also true, however, that numerous and widespread epidem- ics of scurvy, as well as a great number of smaller outbreaks, have run their course entirely without hemeralopia ; and that, finally, hemeralopia has also been repeatedly observed alone without scurvy. In our judgment, therefore, both those au- thors who simply deny any and every connection of night- blindness with scurvy (Friedel), and those who maintain that hemeralopia is, without qualification, to be set down as a phenom- enon of scurvy (Delfort, Blanc, Bumpfield, Hulme, and many others), are equally in the wrong. The most that can be con- cluded from the facts at our command is, that, among the as yet but little studied causes of hemeralopia, there are some which relatively often exist side by side with, and are perhaps, indeed, in part identical with the causes of scurvy, and that, under such circumstances, an epidemic of hemeralopia as well as one of scurvy frequently arises (Bryson, Schwarz, and others); or, per- haps, that the existing scorbutic cachexia itself develops a strong predisposition to hemeralopia (Kuettner,1 Duchek). In point of fact, it seems to us that both these possibilities must be admitted to have a part in producing the effect in question, since either one of them alone is hardly sufficient to explain it. On the one hand, the facts that in the frequent cases of coexistence of scurvy and hemeralopia in one and the same circle of men, usu- 1 Pctersburger med. Zeitschrift. Bd. VI. S. 63. 206 IM M E RM AN N. —SC U RV Y. ally only scorbutic persons were attacked by the derangement of the sight, healthy persons escaping (Schwarz, Kuettner, Duchek), and that, as repeated observations prove, the hemeralopia disap- peared under an exclusively antiscorbutic treatment either simul- taneously with or soon after the scurvy (Schwarz, Kuettner), demonstrate conclusively the existence of a genetic connection between the two diseases. On the other hand, however, the occurrence of entire epidemics of scurvy without a single case of hemeralopia, and the analogous occurrence of isolated heme- ralopia without scurvy, prove that, in addition to the usual causes of scurvy, other peculiar concomitant causes must be pres- ent to occasion de facto the derangement of vision in the patients who are already predisposed to it. At present it is unfortu- nately still impossible to describe more closely the nature of these special genetic influences, and also to say on what the predispos- ing influence of scurvy actually depends. It does not seem to us altogether correct to consider the hemeralopia as simply the effect of the prostrated condition of the general nutrition (Duchek), since anaemic marasmus does not of itself usually lead to hemeralopia in other cases. The occurrence of hemeralopia in the course of scurvy is not confined, as it was once thought, to epidemics of scurvy at sea and in the tropical regions; it has been also observed in recent times in epidemics on land, and where the disease has prevailed on shipboard in the temperate zones. Thus, it was observed in numerous cases during the epidemic in the work-house at Prague (Cejka), and during the epidemic at Rastatt (Opitz) ; it was also observed by Kuettner, in the prison at St. Petersburg (1864), in 18 out 140 of the prisoners who were suffering from scurvy, etc. It was also met with as a complication of scurvy, according to the reports of the English navy, not only at tropical fleet stations, but also at the naval stations in the Mediterranean and in the irregular service (Friedel). It was, however, much more frequent at the tropical stations. These reports, nevertheless, show that the hemeralopia is not immediately dependent on the scurvy. For, at the Australian station, where, during the period of twenty years from 1845-1865, scurvy was most prevalent in the English ships, hemeralopia was entirely absent, whereas at three other stations this disorder occurred more frequently than the scurvy. Both affections, therefore, present evident points of contact and even very remark- able coincidences, but, on the other hand, in many cases such disparity of behavior that it is as yet exceedingly difficult to determine with any accuracy their relations to each other. DIAGNOSIS. 207 Diagnosis. The diagnosis of scurvy does not in general present any great difficulties. As the disease rarely attacks isolated individuals, and usually occurs in the form of an epidemic on shipboard, in fortresses, or in camps, or as a prison or asylum pestilence, the individual case of scurvy under observation is, as a rule, only one among several or many. This cumulation of similar affec- tions, within certain limits of time and space, facilitates in no small measure the correct diagnosis of each new case. It is a very noticeable fact that those affections with which scurvy in its clinical manifestations presents the closest resemblance, and for which it might most readily be mistaken, namely, haemophilia and morbus maculosus (see the following chapter), behave in this respect in a totally different manner. The other diseases of a hemorrhagic character which might perhaps, in addition to the two just named, come into question in the differential diag- nosis, namely, leukaemia, pseudoleukaemia (anaemia splenica et lymphatica), and progressive pernicious anaemia, do not belong in the category of pestilences. The etiological conditions also are of value in aiding to establish the diagnosis. Scurvy is in the first place, as we have already frequently remarked, unlike haemophilia, neither a congenital or hereditary disease, nor an habitual anomaly of the constitution ; on the other hand, unlike the majority of the cases of morbus maculosus, its origin is not apparently spontane- ous. On the contrary, in almost every epidemic of scurvy, and also pretty constantly in the less common isolated cases of the disease, the anamnesis proves that the bodies of men or the single individuals attacked have been previously exposed for a shorter or longer period to the influence of certain anti-hygienic conditions. While speaking of the etiology, we described in detail the special nature of the pernicious influences which produce scurvy. At present, therefore, it will be suffi- cient to recall briefly to the memory of the reader the most important of these. First in importance is the want of fresh vegetable food ; in the second rank we may mention the want 208 IMMERMANN.—SCURVY. of fresh meat, the use of spoiled food, and putrid drinking-water, a long continued sojourn in close, damp, and dark quarters, or in the open air during damp, cold weather, with insufficient clothing, over-exertion of the bodily powers, depression of spirits, etc. The amount of consideration which is to be paid to these anti-hygienic conditions, in making the diagnosis, must cor- respond with the greater or less degree of importance which they possess as causes of the disease. When we have to deal with isolated cases, the diagnosis of scurvy should, as a general rule, not be definitively made unless it is justified, not only by the entire clinical picture, but also by the etiology of the existing affection. Among the local symptoms of scurvy, the peculiar affection of the gums, with its previously mentioned characteristics, must be put prominently forward as important for the diagnosis ; not only because it is by far the most frequent, and for the most part, too, the earliest of all the localizations of the general dis- ease, but also because it is almost never met with in precisely this particular form, in any other hemorrhagic disease than scurvy. It is true that simple bleeding from the gums is by no means rare in haemophilia, and even in morbus maculosus, and that it is also observed quite frequently in the course of leukaemia, pseudoleukaemia, progressive anaemia, etc. In all these morbid conditions, however, we almost invariably miss that inflammatory loosening and spongy consistency of the bleeding gums, which, together with the disposition to hemor- rhage, form such regular characteristics of the scorbutic affection of the mouth. Leukaemia forms the only exception to this rule. In it we sometimes meet with a hemorrhagic inflammatory affec- tion of the gums, the gross clinical picture of which seems, according to the description, to be similar to that of the stomati- tis gingivalis of scurvy (Ollivier). Mosler ascribes it to the irritat- ing action of the saliva, which in leukaemic patients becomes morbidly altered in its chemical constitution. This leukaemic stomatitis—in which, be it mentioned in passing, Ranvier has recently discovered by microscopic examination, in addition to interstitial extravasations of blood, a filling-up of entire capillary districts of the gums with colorless white blood-corpuscles—is, DIAGNOSIS. 209 > however, of very rare occurrence, and even when present, it can- not, if proper care be exercised, easily lead to a confounding of the existing leukaemia with scurvy. For it seems that the affection of the gums in question only occurs exceptionally in very advanced cases of leukaemia, and in these cases the con- dition of the blood, as well as of the spleen and the lymphatic glands, always presents sufficiently clear proofs of the nature of the disease to dispel immediately any doubts which the physi- cian might entertain. On the other hand, however, as we have already mentioned, the affection of the gums may be entirely wanting in scurvy. This is especially apt to be the case when the patient has lost his teeth ; the part of the mucous membrane of the mouth in question is then usually very slightly or not at all affected. This irregularity in the type of the disease will not, however, prevent a correct diagnosis, provided only the disease be in other respects, as regards etiology and symptomatology, sufficiently well marked. Next to the gums, the externed skin is unques- tionably the part in which the localizations of scurvy occur with the greatest frequency ; and since the various purpuric eruptions which make their appearance on it are also undoubtedly the most perceptible to the senses of all the symptoms of the dis- ease, it is natural that, altogether independently of their rela- tions to the scorbutic affection of the gums, great importance should be attached to them in forming the diagnosis. We can certainly maintain, without fear of error, that the presence of an abundance of the hemorrhagic eruptions, which have been described in detail in another place, adds much to the security of the diagnosis of scurvy in individual cases. An entire ab- sence of any and every purpuric eruption speaks with equal force against the existence of this disease. On the other hand, however, no pathognomonic signification can be ascribed to those forms of purpura which are most frequently observed in scorbu- tic patients, namely, to the simple hemorrhagic petechiae, ecchy- moses, and vibices, even though these more common kinds of interstitial cutaneous hemorrhages, like the inflammatory extra- vasations which will presently be mentioned, occur with especial predilection on the lower limbs, and are often limited entirely to VOL. XVII.—14 210 IMMERMANN.—SCURVY. these regions of the body. It is well known that the pathologi- cal domain, within which such suggillations of the skin of greater or less extent may and indeed often do occur, is much more extensive than that of scurvy alone. Hence, even when the simple hemorrhagic eruption is exceedingly abundant, we can only conclude from it that a hemorrhagic diathesis exists in the case under consideration ; for the exact diagnosis of the special variety of the disease, we must rely on the remaining symptoms, with what help can be derived from the etiology of the case. The case is somewhat different with the hemorrhagic inflamma- tory eruptions, particularly those which we have described in another place under the names of Pemphigus scorbuticus and Rupia scorbutica. These varieties of purpuric eruption, as is evident from the qualifying adjective we' have used, occur, so far as is known, almost exclusively in scurvy—hardly ever in other hemorrhagic diseases ; their presence, therefore, furnishes a much more certain proof of the existence of the former disease than is offered by the appearance of petechiae, ecchymoses, and vibices. The syndrome of scurvy is still more characteristic in all those severe cases in which, in addition to the gums and the skin, other parts of the body and other tissues, namely, the sub- cutaneous stratum, the muscles, the serous membranes, the peri- osteum of the bones, and the articulations, are affected in the manner we have already described. We may state explicitly that neither the peculiar, board-like infiltration of the subcu- taneous connective tissue, nor the hemorrhagic inflammatory foci in the muscles, nor the enormous effusions into the serous cavities, etc., which are so frequently met with in scurvy, com- bine with any frequency to form a united clinical picture in any other disease. It may therefore be affirmed, in regard to the local symptoms of scurvy, that the facility with which the diag- nosis is made from them alone increases with the number of tissues affected, and the distinctness of the inflammatory as well as of the hemorrhagic character of the existing local lesions. Finally, the state of the general health is also of very great importance in the diagnosis of scurvy ; in many cases, indeed, it is absolutely decisive. In contrast especially to haemophilia and morbus maculosus, two hemorrhagic diseases which are DIAGNOSIS. 211 characterized by the absence of any real cachexia, or in which, at least, a cachexia is only developed as a complication in the later stages, in consequence of the loss of blood, the great major- ity of the cases of scurvy, as we have already stated, are ush- ered in by a morbid derangement of the general health, which, in addition to a greater or less disturbance of the subjective sensa- tions and of the capacity for bodily exertion, produces an exquisitely marked cachectic change in the appearance of the patients. It is usually only after this initial stage has lasted for a time—in other words, after the cachexiei already exists, that the local symptoms of the hemorrhagic inflammatory diathesis break out in various parts of the body, especially in the gums and the skin, and, by their combination with the general de- rangement, complete the hitherto incomplete clinical picture of scurvy. It is evident, therefore, that, like the etiology and the local symptoms, the state of the general health also constitutes an important point of difference between most cases of scurvy on the one hand, and cases of haemophilia and morbus maculosus on the other, and that it can be made useful in the differential diagnosis of these different, but nevertheless symptomatic-ally related affections. It must, indeed, be admitted that in mild cases of scurvy the initial cachexia may be but little developed, or even almost entirely wanting; but nevertheless, this excep- tional behavior in single cases must not by any means be thought to diminish the general trustworthiness of the diagnos- tic rule just formulated. On the contrary, for the correct appre- ciation of such anomalous cases, it is only necessary to take sufficiently into consideration the fact, that even when the cachexia is absent, the diagnosis can invariably be made with the greatest probability, provided the case in question occurs during the prevalence of an epidemic of scurvy, and evidently under the influence of causes that are liable to produce that dis- ease ; and provided, further, the existing hemorrhagic inflamma- tory local symptoms (in the gums, the skin, the subcutaneous connective tissue, the muscles, etc) are of such a nature as to make any other diagnosis seem absurd. On the other hand, the primary cachexia, which is almost always present in scurvy, produces a certain resemblance between 212 IMMERMANN.—SCURVY. this disease, in its clinical behavior, and leukaemia, pseudo- leukaemia, and progressive pernicious anaemia, in so far as the hemorrhagic diathesis in these three morbid processes is always developed secondarily to a severe general illness. Notwithstand- ing this, however, scurvy cannot be easily mistaken for leukae- mia and pseudoleukaemia ; it is easier to conceive the possibility of its being occasionally confounded with pernicious anaemia, especially as unfavorable outward conditions of existence some- times play a certain part in the etiology of this last process. In addition, however, to the fact that progressive pernicious anae- mia has never yet broken out epidemically as a pestilence in any locality, there exist, as a rule, enough outward points of differ- ence between it and scurvy, to distinguish clinically in a satisfac- tory manner each of these two diseases from the other, and con- sequently, to serve for a differential diagnosis. We may men- tion, for instance, in this connection, that patients with perni- cious anaemia present an excessive pallor ; scorbutic patients, on the contrary, rather a cyanotic (livid) hue; that, moreover, the bleeding in pernicious anaemia is a simple hemorrhagic phenome- non, while in scurvy it is frequently the accompaniment of local inflammatory processes, etc. Finally, useful diagnostic points can also be obtained ex juvantibus, since appropriate treatment is capable of producing extraordinary results in scurvy, while up to the present time every sort of treatment that has been tried in leukaemia and pseudoleukaemia, as well as in progres- sive pernicious anaemia, has proved almost entirely useless. Duration. Terminations. Prognosis. The duration of scurvy is scarcely ever short. It is influenced very essentially, however, by the outward circumstances in which the patients exist during the course of the disease. The longer, namely, the patient, after the attack has commenced, remains exposed to those anti-hygienic influences to which the devel- opment of the disease was especially due, the more severe does it usually become, and the longer, in particular, is its duration, supposing of course that the life of the patient is pre- served, and that at some later period a favorable change takes TERMINATIONS.—PROGNOSIS. 213 place in the conditions of his existence. When this change occurs, a turn for the better usually sets in rapidly, even in very severe and apparently desperate cases. Even then, however, a consider- able time elapses in almost every case; and indeed, when the attack is very severe, many weeks, as a rule, pass by before the disease can be considered as ended and the bodily powers as fully restored. When the disease terminates fatally, its duration is, it is true, more or less shortened by the decease of the patient; still it is in general rare for death to ensue very soon after the scorbu- tic symptoms make their appearance. The rule is rather that the really dangerous accidents which bring about the dreaded catastrophe only appear after the symptoms have persisted for a considerable length of time. In recent times, since we have learned how to guard better by prophylactic means against the conditions which produce scurvy, and, moreover, how to treat the disease appropriately after it has once made its appearance, the termination has been much oftener complete or incomplete recovery than death. Experience has shown that the shorter the duration of the disease, the less fully developed its symptoms, and the sooner especially the patient comes under appropriate treatment, so much the greater is the prospect of complete restoration to health. The way in which the retrogression of the local symptoms and the restoration of the normal general condition take place in these mild cases, has been fully described in the section on the symptomatology. In a similar manner, only much more slowly, a gradual involution of all the morbid symptoms often enough takes place even in the more severe cases, and continues until all trace of the disease has disappeared, provided the requisite removal from the etiological influences has been accomplished before it was too late, and provided, moreover, nothing is neglected in the symptomatic treatment of the foci of disease. At other times, however, even under the circumstances just named, the recovery is incomplete, because local processes have been developed, while the scurvy was at its height, which are incapable of a complete resolution. Among these we may mention particularly, extensive loss of substance by ulceration of the gums, which under the most fortunate circumstances can only be replaced by a cicatricial 214 IMMERMANN.—SCURVY. formation, or abnormal development of connective tissue in the inflamed and swollen mucous membrane, inducing a lasting thickening and induration of the gums ; further, processes of a destructive nature in the skin, which leave cicatrices, or firm connective-tissue growths in the subcutaneous tissue, which often produce secondary atrophy of the muscles beneath, as well as false anchylosis of the neighboring articulations (especially the knee- and ankle-joints). Finally, among the cases of incomplete recovery belong also those which leave behind suppurative pro- cesses in the joints, or true anchylosis, or necrosis of the bones and cartilages, as well as those in which extensive adhesions form between the lungs and the pleura costalis, or the heart and the pericardium, as the results of a pleuritis or pericarditis scorbutica. Death results in scurvy, as has been already mentioned, for the most part only after the disease has lasted for a long time, and when the localizations are numerous and severe. It is there- fore usually the indirect result of an unabated persistence of the causes which give rise to the disease. The fatal result is in most cases directly due to a general functional exhaustion of all the vital organs, which is manifested by the signs of the most complete universal prostration. Less frequently the final catastrophe must be ascribed directly to some unusually severe, and at the same time, on account of their situation in vital organs, especially dangerous localizations or complications. Among the dangerous local affections should be mentioned par- ticularly : hemorrhagic exudations into the pleural and the peri- cardial sacs, and the scorbutic affection of the large intestine, as malignant complications; on the other hand, we must men- tion especially the infectious form of dysentery and croupous pneumonia. Still another mode of death in scurvy is that by acute anaemia, or by bleeding. Death from this cause may occur at any stage of the disease, and may be due immediately, just as in other forms of the hemorrhagic diathesis, to excessive bleeding from cutaneous ulcers, or to an epistaxis which cannot be checked, or to hemorrhages from the stomach or to profuse losses of blood from the urinary passages and the genital organs. Although the number of cases of scurvy which end fatally in TERMINATIONS.—PROGNOSIS. 215 this way is not very small, still this cause of death does not play so important a part in the general mortality of scurvy as it does, for instance, in that of haemophilia or of morbus mac- ulosus ; it does not, therefore, deserve to be mentioned and counted as belonging in the first rank of the various modes in which the fatal issue has been observed to take place. Finally, we must also mention that, even during the earlier stages of the disease, and when, moreover, no special anatomical lesion of serious character exists, many scurvy patients have suc- cumbed in an unexpectedly sudden manner to paralysis of the heart, with the symptoms of syncope. This has happened espe- cially when the patients were obliged to make some violent movement, to stand up suddenly, etc. Hence, neither the extent nor the intensity of the demonstrable gross lesions can serve alone in every case as the measure of the degree of danger which is actually present. This depends also to a very great extent on the intensity of the general weakness, as well as on the occurrence or non-occurrence of external accidents which might occasion paralysis of the heart. It is evident, from what has just been said, that the prognosis in scurvy is dependent upon very various circumstances. First and foremost, of course, it depends on the duration and severity of the case, the severity being estimated by the condition of the general strength of the patient, and by the site, the extent, and the intensity of the local processes; in the second place, on the possibility of procuring appropriate therapeutic aid and of plac- ing the patient under the external conditions that are necessarjr for his recovery. Finally, even in mild cases that are progress- ing favorably, and in which all the dietetic and therapeutic measures necessary for the patient's recovery are being employed, we should always bear in mind the possibility of the occurrence of the dangerous accidents alluded to above, by which life may be very suddenly and unexpectedly jeopardized. A favorable prognosis should, therefore, never be too confidently given in advance, even where the circumstances appear in general pro- pitious. The patient should .at all events never be declared entirely out of danger until unmistakable signs of far advanced convalescence are given by the force and strength of the heart's 216 IMMERMANN.--SCURVY. action, by the renewed vigor of the other organic functions, and finally by a nearly complete retrogression of all the local pro- cesses. Treatment. In speaking of the etiology of scurvy, and again in what immediately precedes, we have repeatedly referred to the great and blessed influence which wise and provident attention to cer- tain sanitary needs in unusual seasons and circumstances, to- gether with the adoption at the proper time of appropriate treat- ment, exert in limiting the development of this disease and in giving to its course a more favorable form. It ma}^ be boldly asserted, that in the whole province of special pathology there are few morbid processes in which a well directedprophytaxis and a strict compliance with the indicatio causalismre able to accom- plish so much, as in the case of scurvy. It is true that our theoretical knowledge of the mode of origin of this affection, as well as of the manner in which the measures that are recom- mended in its treatment act, is at present deficient in many points ; but fortunately this hiatus does not seriously interfere with the success of the prophylactic and therapeutic measures. It is an historical fact that scurvy has become much less frequent, and has lost much of the malignancy which formerly distin- guished it, since physicians learned to deduce, from the knowl- edge gained by experience in regard to its etiology, some evi- dent conclusions as to practical methods of preventing and com- bating the dreaded evil. The prophylaxis of scurvy includes, in the first place, like that of anaemia, a very large part of the domain of general, public, as well as private hygiene, since everything which tends to improve the outward conditions of existence of individuals, as regards their nourishment, habitations, clothing, employment, etc., and serves to elevate the physical condition of a popula- tion, not only increases in general their capital stock of health, but may be regarded at the same time as a special preventive of scurvy. Experience has abundantly proved that scurvy never was prevalent among persons whose outward conditions of exis- TREATMENT. 217 tence at the time could be called normal; this much is also cer- tain, that the liability of an attack of scurvy is not particularly great in the case of any man who is free to satisfy his more important hygienic needs, and understands how to make a fit- ting use of this freedom ! It may, indeed, be safely asserted that any man is safe from scurvy who is able to command a sufficiently abundant and at the same time varied and nutritious diet, and plenty of good, pure, drinking water; who has, more- over, the good fortune to possess a roomy, light, and dry dwell- ing, and can protect himself by proper clothing from the inclemencies of the weather, and who, finally, can preserve his mind in a quiet and cheerful frame, and is neither forced to over- exertion of the body nor yet obliged to pass his life in complete physical inactivity, and that this immunity will persist so long as he continues in the unhindered possession and enjoyment of all these essential requisites to health. And as it is the positive duty of every sanitary board to secure these hj^gienic advan- tages for as many as possible and in the most thorough manner possible, it follows that the prophylaxis of scurvy necessarily coincides in ordinary limes and under ordinary circumstances with general sanitary measures. The question of the preven- tion of scurvy assumes a more concrete form for the most part only under certain conditions of existence, which may all be considered as exceptional in their nature, and therefore, from the standpoint of strict hygiene, as anomalous. Let us there- fore, without further digression, enter at once upon the consid- eration of these somewhat less usual conditions of physical existence, which are well known to involve for certain reasons an outward predisposition to scurvy, and let us briefly discuss, as an addition to what has been previously said under the heads of the history and etiology of scurvy, the most important of the things that can be stated and recommended as of proved value, in regard to the prophylaxis of scurvy under such circum- stances. Here again our attention is naturally first called to the occur- rence of this affection on shipboard, and we must consider by what precautions its breaking out at sea can be most surely prevented. Since the great liability to contract scurvy on a voyage in former 218 IMMERMANN.—SCURVY. times was undoubtedly due to the sort of provisions with which ships were then supplied, and since, moreover, in recent times the disease has scarcely ever appeared on shipboard until after the fresh meat, the green vegetables, and finally, the store of potatoes, had been gradually exhausted, and the crew had been confined for a considerable period to the so-called " sea-food," the prophy- laxis of the disease evidently consists first of all in supplying ships, before sailing, with an abundant provision of good pota- toes, which are the most easily procured and preserved of all the antiscorbutic aliments. It is no less advisable to replenish the store of potatoes as often as necessary at intermediate stations, so as to prevent, if possible, any scarcity of this article of food in the daily ration of the sailors. The preservation of large quan- tities of green vegetables (in hermetically sealed cans, etc.) is, of course, much more difficult and especially much more expensive, and the regular distribution of this sort of food to the whole ship's company would hardly be practicable as a permanent thing, particularly on board of merchant vessels. It is hardly necessary to say that, whenever by a fortunate combination of circumstances it is possible to obtain fresh vegetables during a voyage, the opportunity should never be neglected; the crew should be encouraged to indulge freely in them at the time, and a supply should also be laid in for future use. For reasons that are easy to understand, the renewal of a ship's supplies of green vegetables becomes a matter of the greatest difficulty in the case of voyages to the barren polar regions and of lengthened sojourn there. A few moderately palatable, nutritious plants, such as the spoonwort (Cochlearia officinalis), the common sorrel (rumex acetosella), the dandelion (taraxacum oflicinale), the house-leek (sedum acre), and some other species are, however, found among the scanty vegetation of those regions, and when the voyage falls in the short polar summer, the men should be encouraged to gather these plants and to use them as vegetables or salads. We venture to doubt whether the spoonwort, so much vaunted in former times, and even yet, as a prophylactic against threatened and a specific for existing scurvy, really possesses any "very special" antiscorbutic powers, and do not believe that this power, if it exists, resides in the sulphuretted ethereal oil of this TREATMENT. 219 cruciferous plant. We are disposed rather to account for the important and gratifying role which spoonwort has unquestion- ably played in the history of the prophylaxis as^well as of the treatment of scurvy, simply by the circumstances that the re- gion of distribution of this plant extends unusually far to the north, and that mariners in the higher latitudes, when seeking for vegetable food on the barren strips of coast of the arctic regions, very frequently found this spoonwort and often nothing else. The plant is found, according to Mertens, Egede, and others, in incredible quan- tities on the coasts of the extreme north (Spitzbergen, Greenland). It thrives even in sand or on almost naked cliffs, wherever even minute quantities of the droppings of birds or the excrement of seals have fallen. Its taste is said to be in the polar regions less pungent, but more of a bitter-sweet (Krebel). The dandelion (taraxa- cum officinale), which is so common on our grass-lands, and affords a savory vege- table especially adapted for use as a salad, is also met with by the polar explorers in the very farthest north. It doubtless owes its great reputation as a prophylactic against scurvy principally to this accidental circumstance. We stated, while speaking of the etiology, that bread, dried leguminous vegetables, and rice, although all vegetable aliments, still do not possess the antiscorbutic properties of potatoes and green vegetables. Sauerkraut, however, would seem to be a good and very efficient substitute for these latter in the alimen- tation of the sailor ; of its efficacy in preventing the scurvy, Lind, Mertens, and other earlier writers were thoroughly con- vinced. Lind, in particular, stated that on board of Dutch ships, which were habitually well supplied with sauerkraut, scurvy was unusually rare, and he recommended most urgently that ships should take with them large supplies of this aliment, which, when packed in casks, can be preserved in good condition for 3rears. That this advice of Lind's was really well grounded seems evident from the fact that at the present day English and other marine surgeons always recommend an abundant supply of sauerkraut as well as of potatoes, on sea-going vessels, as one of the principal prophylactic measures to be taken for the pre- vention of the scurvy. It seems worthy of mention in a theoreti- cal point of view, that sauerkraut, as usually prepared, loses nothing of the nutritive elements of the fresh cabbage (especially 220 IMMERMANN.—SCURVY. of its nutritive salts), so that it may in fact be looked upon as a complete, though not a very easily digestible, substitute for the fresh vegetable substance. Finally, let us once more recall to memory the fact, of ethnological interest, that cer- tain peoples (Laps and Finns) dwelling in the far north are able during the long winters to protect themselves successfully from scurvy by the daily use of a substance similar to sauer- kraut—namely, common sorrel, gathered in the autumn and prepared with reindeer's milk. They consume considerable quantities of this substance with the flesh of animals killed in the chase. Other northern peoples who live exclusively on meat, —for instance, the Quaens and Normans,—suffer severely from scurvy. Of other articles of food, juicy fruit certainly approaches most nearly to vegetables in its chemical properties, and like them it is also valuable as a preventive of scurvy. As oranges and lemons are, of all kinds of juicy fruits, the easiest to pack away and to keep in good condition on shipboard, it has become a pretty general custom in recent times to lay in supplies of them on extended voyages, and to deal them out to the crew at inter- vals, in order to diminish the danger of an epidemic of sea-scurvy. The so-called lemon-juice is also employed as a prophylactic against scurvy, in the British and some other navies. It consists of the expressed juice of lemons, clarified, and for its better preservation mixed with brandy in the proportion of 10:1. On every long sea-voyage, even at the present day, each English seaman receives daily, after the first fortnight, 30 grammes (si.) of lemon-juice and 45 grammes (fiss.) of sugar as an antiscor- butic ration. As, however, the lemon-juice, even when prepared as above described, did not always remain good for sufficiently long periods, and as, moreover, in spite of its regular employ- ment, scurvy sometimes broke out on shipboard, it was subse- quently discarded in the Austrian navy, where it had been employed for a time (Duchek). It has also lost much of the favor with which it was temporarily regarded by the naval authorities of several other nations. But, in our judgment, it is not fair to conclude that a preservative is totally useless because it is not entirely sure, or does not protect in every case; and TREATMENT. 221 there is as little justification for the belief that all necessary pro- phylactic precautions have been taken against scurvy by the distribution of any one other article of diet alone. The con- tinued employment of lemon-juice on the ships of the first mari- time power of the world — namely, of England, cannot, as it seems to us personally, be ascribed to a mere conservative whim; on the contrary, it furnishes noteworthy extrinsic evidence that lemon-juice must possess certain antiscorbutic virtues, when employed in connection with a sea-regimen in other respects rational. It must not by any means be imagined, however, as Chalvet very justly observes, that the use of plain citric acid in the form of lemonade, or of lemonades prepared with other vegetable acids, can in any way take the place, as pro- phylactics, of lemon-juice or of the juice of other acid fruits ; or that, for instance, in order to prevent scurvy on sea-voyages, it is only necessary to carry a large supply of crystallized citric acid, which is very easily preserved. According to the state- ments made in another place, it is in the highest degree improb- able that the pure vegetable acids possess any efficacy whatever as direct antiscorbutic agents ; on the contrary, there is good reason to believe that it is only when in the form of their unstable combinations with potassa (precisely the form in which they are chiefly contained in fruits and in many vegetables) that they pos- sess these antiscorbutic qualities. Hence, the fact that vege- table acids, given alone, are worthless both as prophylactic and as therapeutic agents in scurvy (Beckler, Duchek, and others), does not prove anything whatever against the efficacy of the expressed juices of fruits. Of animal food, apart from fresh meat, which should be procured as often as possible when opportunity offers, and the fresh milk of stalled animals (cows), supposing that such live tenants can be accommodated on shipboard, canned meats and condensed milk are to be recommended above all other articles as prophylactics against sea-scurvy. As further substitutes for fresh meat, which at all events are far preferable for sea-diet to the justly decried salt junk, the following might be mentioned : the so-called meat-biscuit, meat-powder, meat preserved in honey casks, or enveloped in sugar, and also meat which has been suit- 222 IMMERMANN.—SCURVY. ably prepared for preservation by immersion for a short time in creosote water. We refer the reader to Krebel1 for further information as to the modes of preserving and cooking these various preparations of meat, all of which, though not in an equal degree, deserve to be recommended as supplies for a sea- voyage. Liebig's Extract of Meat is also to be highly recom- mended. This preparation, although entirely lacking in albu- men, contains otherwise in the greatest abundance and in con- densed form precisely those substances (salts of potassa) which the meat loses most during the process of pickling, and to the want of which modern writers are disposed, not without good reason, to ascribe the frequent occurrence of scurvy after long- continued and exclusive use of salted meat. The history of this disease furnishes numerous examples from former times which seem to support this theory. In the hygienic administration of a ship, the most careful attention must be paid to the condition of the food used, as well as to the choice of the diet, if it is desired to render the protection against scurvy as certain as possible. Spoiled articles of food, whether they be meat, biscuit, or anything else, not only prove decidedly injurious to health by provoking more or less serious derangements of the digestion, but it would also seem that the development of many epidemics of scurvy must be ascribed to the use of such articles in the sea-diet. It is the duty, therefore, of those charged with the supervision of the daily rations of the crew, not only to see that the food used is sufficient in quantity and properly prepared, but also that it is in a good state of pres- ervation ; whatever is suspicious in this latter respect should be promptly discarded, and, if any intermediate stations are made, the deteriorated articles should be replaced by a new supply in the best possible condition. Good drinking-water is also a very important preservative against scurvy at sea. Supplies of drinking-water on shipboard can with a little care be kept from spoiling for a long time ; they should be contained in large, tightly closed, iron tanks, placed in the coolest possible part of the ship. There are, moreover, 1 1. c. S. 232-237. TREATMENT. 223 various methods of more or less value by which foul drinking- water can be purified, either by filtration, or by precipitation of the dirty slime that has formed in it, as well as methods by which drinking-water can be obtained by the distillation of sea- water. The necessary information on these points will be found in Krebel's1 work. Finally, as often as a fitting opportunity presents itself, the store of drinking-water should be renewed, a freshly drawn supply of good spring-water being taken in. This is a duty which must be fulfilled with as much care as the replenishing of the supply of provisions. As other beverages to which we are entitled, by abundant experience, to ascribe a protective efficacy against scurvy, and the daily use of which on protracted voyages is, therefore, desir- able, we may mention especially tea, good beer, particularly the spmtce beer (Sprossenbier), prepared by adding turiones pini s. abietis to the fermenting mash, or essence of spruce to the fer- mented drink ; and finally, wine, or, in place of it, cider. The value of all these beverages, as prophylactic agents against scurvy, may be considered as thoroughly proved by the decrease in the frequency of this disease at sea since they have been generally introduced into the diet lists of ships ; and it is a very striking fact, that, like the antiscorbutic aliments (green vegetables, fruits, etc.), they all are remarkable for the large amount of potassa which they contain in combination with carbonic acid and vegetable acids. This circumstance furnishes still another argument in favor of Garrod's theory, that the occurrence of scurvy is due to an insufficient supply of potassa to the organism. However, the etiology of scurvy does not exclusively or in all cases consist in a faulty supply of food and drink ; and as numerous observations prove that epidemics of the disease can occur on shipboard even when the supply of food and drink is most perfect, it is evident that they must be referred to other injurious causes. Hence, the prophylactic measures to be taken against scurvy at sea should not be limited merely to an appropriate regulation and supervision of the alimentation. It 11. c. p. 240-245. 224 IMMERMANN.—SCURVY. is also essential that strict attention should be paid to all those other injurious influences by which a prolonged confinement on shipboard may be rendered dangerous in this respect. Some of these influences are merely auxiliary, but others are perhaps of cardinal importance. Among them we must mention, in particu- lar, defective ventilation and uncleanliness of the ship, frequent exposure to wet and cold, with the consequent drenching and chilling of the body, excessive hardships, and depression of spirits. Every effort must, therefore, be made to secure under all circumstances the greatest possible cleanliness, so far as this is practicable on board of a ship on a long voyage. Special attention must also be paid to the proper ventilation of the covered spaces in the ship, since a stagnation of air vitiated by all sorts of gaseous emanations in these spaces, seems plainly to have had a direct causative connection with the outbreak of many epidemics of scurvy on shipboard. For this reason alone, apart from the other advantages of good, pure air, it is especially advisable, whenever the temperature of the air and the state of the sea will permit, to open daily the ports of the ship and the cabin windows, so as to secure a free exchange of air. It is of course a very great advantage to have the air in the interior of the ship renewed also during stormy, cold, and damp weather, and for this end various ventilating apparatuses have been pro- posed and employed, by means of which, without opening the windows of the ship, the air can be changed as often as neces- sary.1 The first apparatuses of this sort were introduced by Baskoweh and Ventura. The clothing of the crew is another matter which deserves attention. It should be appropriate for the climate, but in particular should be of such a kind as to protect the body as far as possible from chill and wet. A sufficient supply of woollen shirts and drawers should be in the possession of each man, especially on voyages in the northern seas; in addition, thick outer garments. In regulating the often very exhausting duties of the ship's service, the attempt should be made to distribute by regular reliefs the burden of the general work in such a 1 Krebel, 1. c. p. 227. TREATMENT. 225 way that it may bear as equally as possible upon the shoul- ders of all, and that rest and exertion may succeed each other at suitable intervals. At the same time, however, the indi- vidual's capabilities should be kept in mind as far as possible, and the tasks allotted to the weaker and more delicate members of the crew should not, when it can be avoided, be as severe as those allotted to the stronger and more robust. It must, moreover, always be borne in mind, that notwithstanding a fair distribution of the burden of duty, in which the weaker individuals are favored in some degree, the amount of bodily exertion unconditionally demanded from each one varies very greatly under different circumstances (for instance, it is much greater when the weather is stormy and the sea high than in calm weather), and that the supply of food, as well as of exhil- arating drinks, should be in proportion to the greatness of the exertions called for. Nothing can in fact be more detrimental to the physical well-being of a crew, and more favorable to the development of an outbreak of scurvy among them, than a too rigid adherence to formal regulations which prescribe a uniform and almost unvarying sea-diet, both as regards food and drink, without reference either to the different needs of differently con- stituted men, or to the great variations in the severity of the bodily exertions demanded. There is no other situation in which a certain fluctuation in the amount of the day's rations, gauged on an intelligent knowledge of physiological principles, is as de- sirable, and in a prophylactic point of view as advantageous, as it is on shipboard. Finally, it is also without doubt the duty of those in command, in the trying times and precarious situations which are so often met with on long voyages, to exert to the utmost their moral energy, and to bring into play their intellec- tual endowments, in order to maintain or reawaken courage, endurance, good humor, and a hopeful state of mind in those under their control. The very beneficial influence of these psy- ch iced factors on the health of the crew has been repeatedly and with good reason insisted upon, and from the earliest times they have been considered as specially efficacious in warding off the attacks of scurvy. The preceding remarks can only be looked upon as a very general and incomplete outline of the precautions VOL. XVII.—15 220 IMMERMANN. —SCURVY. that must be taken by the officers charged with the superinten- dence of the ship's hygiene, in order to guard as far as possible against an outbreak of scurvy—that formerly so dangerous and even at the present time so threatening enemy of the sailor. For further details in regard to prophylactic measures, we must refer to the works which treat specially of this subject, in particu- lar to Krebel's monograph. We shall only add, in addition to what has already been stated, that in many cases unexpected occurrences will make it necessaiy to abandon for a time some one or more of the elements of the prophylaxis, but that natu- rally the possibility—indeed, the probability of an outbreak of scurvy then increases in a corresj)onding measure, and eventu- ally perhaps the disease actually makes its appearance. Hence, sea-scurvy, as a topological variety of the disease, does not as yet belong entirely in the domain of history. In addition to the question of its prevention, that of its treatment will in all probability long continue to occupy the attention of naval au- thorities and ships' surgeons. The prophylaxis of the so-called laud-scurvy, or, more cor- rectly speaking, of this disease when occurring on land, for in its nature it is entirely identical with sea-scurvy, falls princi- pally in the domain of military hygiene. The reason for this is, that this variety of the disease, as history proves, has occurred both in ancient and recent times with special frequency and de- structiveness in besieged cities, as well as during long marches and military operations performed under circumstances of un- usual difficulty—in short, as a result of the incidents of war. The measures to be adopted for the prevention of scurvy in time of war should be dictated, in the first place, by a prudent fore- sight in regard to the possibility of towns being besieged. With this possibility in view, these measures should consist principally in provisioning as abundantly as possible all fortified places, particularly with sufficient supplies of those easily preserved aliments and drinks—for instance, potatoes, sauerkraut, con- densed milk, and wine—which possess unusual antiscorbutic efficacy; secondly, in securing a sufficient number of cattle and horses, with the necessary quantity of dry fodder (oats, hay, etc.), in order that the besieged garrison and the civil population may TREATMENT. 227 have fresh meat to eat as long as possible ; thirdly, in a strict examination and repeated inspection of all springs and perma- nent sources of water-supply in the fortified place, in order to prevent contamination of the drinking-water by filth or effluvia; finally, when the place is really besieged, in a regulated distribu- tion of food and drink to the troops, comprising the garrison and the inhabitants, in relieving at proper intervals the troops who are charged more specially with the duty of defence, and last, but not least, in the employment of the moral influence of the commanding officers for the encouragement of the defenders and of the citizens as soon as any abatement is noticed of the heroism manifested at the beginning. It cannot, however, be denied that, even with the help of all the material as well as mental and moral forces, it is not always possible to prevent permanently the outbreak of scurvy in a besieged town, and that the prophylaxis of the disease, iu this field of its special predi- lection, will constantly encounter difficulties, if possible, still greater than in the field of maritime expeditions. It neverthe less forms a most important part of the duty of all prudent strategists to meet this powerful ally of the enemy by the most energetic employment of all available forces, and by the most intelligent foresight in the directions that have been pointed out. We need not insist on the necessity of supplying troops operat- ing in the field, more particularly during a winter campaign, with sufficient stores, which should be supplemented by additional supplies of food, wine, warm clothing, etc., sent to the soldiers from their homes. The great facilities of communication in modern times render the proper maintenance of troops, at least- while operating in civilized countries, much more feasible at the present day than formerly. It is probable that to this external circumstance is due in no slight degree the fact that scurvy has been so much less frequent during the great wars of the latest times, during which, apart from its occasional prevalence in besieged fortresses, it has only showed itself in very rare instances among bodies of troops operating in the open field. In order to guard against the possible occurrence of scurvy as a pest Hence in prisons, or as a local epidemic in alms-houses, foundling asylums, barracks, etc., it is of the first importance 228 IMMERM A N V. — SCURVY. that the food provided for the inmates should be sufficiently abundant and not too monotonous, and particularly that ir should not too exclusively consist of bread and dried legumi- nous vegetables; a constant and abundant supply of good, clear drinking-water should also be furnished. In the next place, we must recommend, as of hardly less importance than a proper supply of food and drink, a careful attention to clean- liness, and particularly to the proper ventilation of the cells and inhabited rooms. Finally, a certain, not too limited amount of exercise in the open air, is of the utmost advantage, especially in the case of prisoners who would otherwise be forced to pass the whole day in sedentary occupations in their place of confine- ment. Without this exercise the body is liable to become pre- maturely infirm, and thus more predisposed to attacks of scurvy. When, on the other hand, prisoners are required to perform, for any length of time, work demanding much greater exertion of bodily strength than they are accustomed to—for instance, in erecting buildings, agricultural labors, etc., the hours of labor should not be excessive ; and in proportion to the labor required, the ration should be improved by the addition of meat, green vegetables and potatoes, as well as milk and beer or wine. Experience has sufficiently proved that the neglect of these measures, under such circumstances, has relatively often been followed by outbreaks of scurvy among prisoners. Finally, we would further observe that, whenever it is necessary to build a prison, hospital, alms-house, barrack, or any other building destined to serve as a place of more or less compulsory abode for large numbers of human beings, the very greatest possible attention should, as a matter of course, be paid to the dryness and roominess of the localities to be occupied by the future in- mates. Care should also be taken to secure a good location for the proposed establishment, both as regards the nature of the subsoil and the facilities offered for the free admittance of light and air—in short, everything should be attended to in the ex- ecution of the plan, which can in any way tend to increase the salubrity of the institution. Lastly, the prophylaxis of scurvy demands also that, in years in which, owing to bad crops, especially of potatoes, a pandemic TREATMENT. 229 spread of scurvy among the poorer classes of any country is threatened, public charity and even direct government help should come forward and make up for the failure of the crops by procuring the necessary supplies of vegetable food from other countries ; also that private and public assistance must do their utmost to alleviate any other material misery, whatever it may be, that threatens at any time to undermine the general health of the people. For, although all kinds of external privations may not lead with equal readiness to the development of an epidemic of scurvy, still all do, indirectly at least, contribute to its pro- duction, since they all lessen the power of the organism to resist disease, and thus, by preparing the ground, enable the real causes of scurvy to exert their noxious influence more potently. The medical experience of the present century has taught, at times in the most distinct manner, that a comprehensive and at the same time energetic administration of the hygienic princi- ples which have just been described, raises an exceedingly strong barrier against the development of scurvy, both at sea and on land. In the first place, epidemics of scurvy of such intensity and extent as were formerly of frequent occurrence, have been very rare of late years. Moreover, whenever, either from sim- ple neglect or from necessity, one or other of the more impor- tant of the precautions mentioned has been left unattended to, and, in consequence of the omission, an epidemic of scurvy has broken out, the subsequent elimination at the earliest possible moment of the offence against sanitary laws has almost always proved to be a sure and unfailing means of preventing the fur- ther extension of the pestilence. It has also been proved by numerous observations, that these hygienic measures exert not only a prophylactic, but also a very important directly cura- tive action, since they constitute, when carried out with great strictness and properly adapted to the etiology of each indi- vidual case, the groundwork of the causal treatment. We have already repeatedly stated that, in addition, a rational prophy- laxis, a strict compliance with the inelicatio causalis, of which we shall presently speak, has proved itself to be not merely in some degree, but indeed in the highest degree, effective. It is, therefore, sufficient for the present to call to mind once more, 2H0 IMMERMANN.—SCURVY. that a rapid change for the better takes place invariably in mild cases, and with striking frequency even in the severest cases of this disease, as soon as the treatment succeeds in doing away with the exciting causes of the disease. But the thorough fulfilment of the indicatio causalis presup- poses in the first place an actual knowleelge of the causes of the disease, in concreto ; a mere theoretical acquaintance with the injurious influences, which may in general give rise to scurvy, is not sufficient. Hence, an accurate etiological investigation is essential for a rational and successful treatment in individual cases as well as in individual epidemics of scurvy. This exami- nation must determine the special causative factors that have been active in each case, and make them serve as a basis for the plan of treatment to be adopted. It will not do to enter upon the causal treatment of scurvy with any preconceived ideas as to the exclusive agency of some one or other exciting cause, nor to base the treatment, wherever an epidemic of scurvy prevails, always on the same etiological plan ; on the contrary, it must be constantly borne in mind that not even the pathogenesis, much less the etiology of scurvy, can be said to be uniform. Even though, for instance, one particular peccant circumstance— namely, the deprivation of fresh vegetable food, seems to have played with common frequency the part of the exciting cause, and although the very numerous cases and epidemics of scurvy thus produced can be cured more rapidly and surely by imme- diately supplying the aliments of which the patients have been deprived, than by any other means ; still, it would be very absurd to regard salad, green vegetables, and potatoes on this account as a uni versed remedy for scurvy. On the contrary, the history of the disease contains many examples which prove that epidemics may also at times arise, spread, and attain great proportions even when the supply of fresh vegetables is perfectly sufficient, and that, as we may at once add here, the curative efficacy of the articles of food mentioned, although undoubted in very many, is by no means evident in all epidemics and isolated cases. Wherever the scurvy is to be attributed in concreto to the influence of other causes, the fulfilment of the indicatio cau- salis demands, a priori, other therapeutic measures, and experi- TREATMENT. 231 ence has shown, moreover, that such other modes of treatment are often much more efficacious than an increase in the sup- ply of juicy vegetables. This is particularly true, in regard to the treatment to be employed in all those epidemics, the etiology of which points to unhealthy conditions of the habitations occu- pied by those attacked rather than to defects on the part of the alimentation. In such cases it has been many times demon- strated, that a transfer of the patients to more healthy (lighter and dryer) habitations proves a means of cure as much to be relied upon as the change to a correct diet in those, much more numerous, cases, in which the disease is due to improper or insufficient food. A very instructive instance of this is to be found in the rapid improvement and recovery of all the scurvy patients of the low-lying and damp military hos- pital at Givet (1847), as soon as they were transferred to a neighboring height, although no other treatment was adopted. We cannot spare time here to enter again into the details of the measures required to carry out the indicatio causalis in each particular case. We must refer to the full statements given under the head of Etiology, for an account of the prejudicial influences, the elimination of which may be desirable in the indi- vidual cases, and to those given under the head of Prophylaxis, for an account of the measures to be adopted. It seems to us very doubtful whether there is or ever can be any essential mode of treatment for scurvy apart from the causal treatment, the success of which, however, when properly indi- vidualized and sufficiently energetic, is exceedingly gratifying. It is true, that the search after such a mode of treatment has seriously occupied the attention of physicians, especially in former times, and that many different remedies and methods of treatment have at various times, some even quite recently, been claimed to possess specific antiscorbutic efficacy. If, however, we admit that neither the etiology nor the pathogenesis of scurvy is the same in every case, and in our opinion this view is the only one that accords with the present state of medical knowledge— or if, to express it in other words, we feel ourselves forced to admit that the collective symptoms of scurvy, identical in a clin- ical point of view, may in different instances be engendered by 232 IMMERMANN.—SCURVY. different external influences and in different ways, we must naturally define and limit more closely the conception of an ikessential" mode of treatment for the disease. The remedy namely, which is to fulfil the indicatio morbi, must be able to exert a decidedly favorable and curative action on the peculiar general cachexia, and the hemorrhagic-inflammatory local symp- toms in all the etiologically different forms of the disease; in other words, independently of the particular mode of develop- ment of the individual case or epidemic. Such an "antiscorbuticum," the radical, therapeutic action of which on scurvy should be about analogous to the action of iron in the treatment of anaemia due to different causes, is, how- ever, as yet wanting in our treasury of remedies, and is, there- fore, still to be found. Instead of it we find mentioned in the history of the treatment of scurvy, apart from the noted very efficacious dietetic directions already described, which serve both for the general proplrvlaxis of the disease, and the special fulfil- ment of the indicatio causalis in the individual cases and epide- mics, only such remedies as either 1), really belong, or at least appear to belong, to a more comprehensive causal treatment, or 2), merely comply with the indicatio sympiomedica. To the first category belongs, for instance, the often recommended, and also often successful, employment of the fresh juices expressed from the leaves, roots, and fruit of different plants, such as the differ- ent varieties of the brassica and nasturtium, the taraxacum, cochlearia, sedum acre and sedum telephium, chelidonium, bec- cabunga, oxalis, and different varieties of rumex—also beets, turnips, carrots, radishes and horse-radish, cherries, currants, lemons, barberries, whortleberries, the fruit of the cornel tree, etc. The administration of these juices, however, is plainly nothing more than the administration of the alimentary sub- stances themselves in a more medicinal form, and the same results will be attained in as certain and thorough a manner by the use of fresh vegetables, salad, and fruit, as articles of diet. The treatment by the juices, moreover, in its nature and its effects is principally a mere compliance with the indicatio causalis in the far greater majority of cases of scurvy. If it is desired to make a therapeutic use of these juices, in severe cases TREATMENT. 233 of the disease, in order to increase the effect of a correspond- ing diet, they should be given in quantities of from 60,0-120,0 grammes (3 ij.-jv.) daily, or, if the case requires it, in still larger quantities. On the theoretical presupposition that it is the organic acids contained in many of the plants mentioned which constitute their curative principle, these acids themselves were recommended as antiscorbutic "remedies." Experiments in the treatment of scurvy patients were accordingly made with tartaric acid, citric acid, and at times with other organic acids; the result of which, however, was on the whole so completely negative that the theory on which they were based was soon demolished. In regard to the presumably active principle of these vegetable substances, namely, the potassa, it is to be regretted that no sufficiently extended and exact series of experiments have as yet been made to determine the therapeutic action of the pure vegetable salts of potassa (bitartrate, citrate, and acetate of potassa). However, Brouardel, on the ground of his own experi- ence during the last Paris epidemic, at all events commends the abundant use of boiled wine, which in the process of boiling has lost part of its alcohol and water, and for this very reason con- tains the bitartrate of potassa in more concentrated form. He also recommends, as do likewise Bucquoy and others, the ad- ministration of the tartrate of iron and potassa. Certain inor- ganic combinations of potassa, in particular nitrate of potassa, dissolved in vinegar (Cameron) or in water (Henderson), and given in doses of from 8,0-15,0 grammes (3 j.-ij.) daily, have also been strongly advocated in former times, as well as quite recently (Pechey). But even if future experience should establish still more firmly and surely the truth of the maxim, that, as a want of potassa in the food is a frequent cause of scurvy, so the salts of potassa, especially those which are most easily disintegrated and assimilated, possess a decided therapeutic action on the dis- ease, we shall still be compelled to ascribe this favorable action to a compliance with the indicatio causalis, and not with the indicatio morbi. In other words, the employment of them as medicaments compensates for the previous deprivation of food, rich in potassa, and eventually arrests the morbid process occasioned by this deprivation. Finally, in the class of remedial 234 IMMERMANN.—SCURVY. agents which probably owe their efficacy to the potassa they contain, we may also count the barm of beer, which has been so largely and at times so successfully employed in the treatment of scurvy. The credit of first introducing this substance as a remedy belongs to Neumann,1 who found yeast wonderfully effective in the treatment of this disease in all its stages, and recommended its administration internally, in doses of from 180,0-300,0 grammes ( 3 vjss.-jxss.) daily. Neumann s favorable opinion has been shared by a great number of physicians and authors (among others Of. S. v. Himmelstiern, Windisch, Fink, F. v. Niemeyer, and more recently Doering), while others again, among whom are Krebel, and particularly Duchek, although they do not deny entirely the usefulness of this substance, rate it, however, in general much lower than Neumann does. If we keep in mind the fact that barm, being a vegetable organism in a state of very active proliferation, is, like all rapidly growing parts of plants, very rich in potassa,- we must admit that its so highly lauded antiscorbutic efficacy appears to be a significant illustration of Garrod's theory; at the same time this richness in potassa, when considered in connection with the favorable results obtained by the use of fresh vegetable food in so many cases of scurvy, explains, to some extent, the efficacy of barm. Finally, it ought not to be a matter of surprise that a remedy usually so valuable should have proved on the whole of so little efficacy in cases of scurvy, which were notoriously not due to any want of food containing potassa in sufficient abundance (potatoes). The cases observed and treated by Duchek were precisely of this character. Let us now turn to those other therapeutic substances which, in our opinion at least, possess only a symptomatic value. Among these we must mention in the first rank the various preparations of quinine, the pure bitters (gentiana), the aromatic bitters (calamus, cortex aurant.) and the aromatics (rad. angeli- cas, rhiz. zingiberis, cortex cinnamomii). It does not seem to us possible that these substances, the beneficial influence of which, on the condition of patients, we are by no means disposed to 1 Hufeland's Journal. Februar 1832. TREATMENT. 235 deny, can exert in cases of scurvy any other than the ordinary tonic and digestive action which they are wont to display in so many other cachectic conditions, and wherever in general there is prostration of the digestive powers. The same is, in our opinion, also true of the tonics, in the more limited sense of the word, namely, of the preparations of iron, which are said to be very useful, especially in severe cases, or when convales- cence is retarded. If we bear in mind that the scorbutic cachexia in its more developed forms leads to pronounced anasmia, and especially oligocythemia, or, to put it in other words, is very usually complicated with this latter anomaly, it will be evident that the favorable effect of iron in some cases is a proof, not that the remedy possesses any actual anti- scorbutic propertj^, but simply that it has been indicated by the symptoms in the concrete cases. About the same may be said, too, in regard to the actual or pretended cures said to have been obtained by the use of the mineral acids (Cooper, and others), particularly sulphuric and nitric acids, or of the ergot of rye (Canuto Canuti, Henoch, Bauer, and others), and of the chloriele of iron (Bouchet, Bourdon). All these medicaments, on account of their more or less proved powers as hazmostedics, were em- ployed tentatively in the milder as well as the more severe cases, against the hemorrhagic diathesis; they were prescribed as in other diseases with a specific object. It is a notable fact, however, that most of the medicaments in question were, on the whole, of no great service in combating the hemorrhagic accidents in scorbutics, at least when given internally. Further than this they did not usually exert any essential influence on the scorbutic cachexia, the eradication of which is of primary necessit}T, since it constitutes the basis on which the hemorrhagic processes, as symptovis of the general disorder, are developed. In any case, therefore, these medica- ments, according to their action must, like the tonics and diges- tives, be classed simply as sjmiptomatic remedies. Finally, it still remains for us to discuss very briefly those measures which are to be adopted in the symptomatic treatment of scurvy, and which are directed particularly against the more serious individual symptoms. Of all the symptoms of 236 IMMERMANN.—SCURVY. the disease, the functional weakness of the muscular appara- tus, and particularly of the heart, which is so intense in the severe cases, is by far the most dangerous, and hence demands the greatest amount of attention in the treatment, The treat- ment of this symptom must be both negative and positive. On the one hand, the greatest pains must be taken to avoid what- ever might still further enfeeble the patient in his already pros- trated condition, while, on the other hand, everything possible must be done to raise him up from this state. In the first place, all directly enfeebling treatment and medication must be avoided, particularly any unnecessary limiting of the supply of food, or the eulministration of the more powerful drastics when consti- pation happens to exist, or tlie employment of an active mer- curial treatment -to combat inflammatory localizations or com- plications (pleuritis, pericarditis, enteritis scorbutica, etc.), or more especially local and general blood-letting. With regard to the use of purgatives, we must mention explicitly that the more active among them (senna, jalap, aloes, colocynth, etc.), not only exert an enfeebling and prostrating action, but in scorbutics readily excite violent hemorrhages from the bowels, which can- not be checked. Hence, whenever in such patients constipation renders the employment of some therapeutic means desirable, an endeavor should be made to evacuate the bowels by the use of clysters, or at most only by the administration of very mild laxa- tives (castor oil, tamarind pulp, bitartrate of potassa). The employment of mercurials is also forbidden, even when in the concrete case they might seem specially indicated for some other reason, for experience has shown that these preparations, in addition to their injurious action upon the general nutrition, almost always exert, after a short interval, an exceedingly unfav- orable influence on the scorbutic affection of the gums, and more- over, usually aggravate the hemorrhagic diathesis. Finally, the direct abstraction of blood by leeches or by the lancet, although it has been occasionally recommended as a means of combating the scorbutic dyscrasia (Opitz), is still in general, and very justly, too, looked upon as absolutely counterindicated in this disease, because of the prostration which it produces. At the utmost it might be allowable as an occasional expedient in those very pe- TREATMENT. 237 culiar and unusual cases where there is a marked disproportion between the quantity of the blood—that is, the burden to be set in motion by the heart, and the momentary capability of the heart muscle to perform this task—or, to state the case more precisely, when extreme and dangerous cyanosis occurs in the course of a still recent attack of scurvy in a previously strong and full-blooded individual. Under these exceptional circum- stances, the abstraction of a moderate quantity of blood by the lancet, or the application of a number of leeches over the left border of the sternum near the heart, may perhaps, sometimes, actually save life, since by a partial depletion of the venous sys- tem the physiological task of the heart will be temporarily diminished. Under all other circumstances, however, the physi- cian must carefully shun these measures which would only aggravate the scorbutic disturbance by the addition of anaemia as a complication; on the contrary, every pains must be taken to preserve the stock of blood as intact as possible. There is still another condition in which the treatment of the weakness of the heart in scorbutics must be rather of a negative or prohibitive character. Whenever, namely, the disease is far advanced and the feebleness extreme, the patient must be pre- vented, as far as possible, from making any movement of the body, and should constantly be obliged to retain a nearly hori- zontal posture in bed. The reasonableness of these precautions must be plain to all. The latter, in fact, is indicated not only in the functional adynamia occurring in the course of scurvy, but in all other adynamic conditions as well, and perhaps i lie only reason why it requires special mention in the symptomatic treat- ment of scurvy is, that in this disease a relatively large number of sudden deaths have been observed, which were due to the imprudence of the patients in sitting up, or standing up and walking about too soon. Finally, the positive measures which must be employed to counteract the feebleness of the heart and the general functional adynamia, do not differ from those which are usually adopted in analogous cases. The use of nourishing food, which must be, however, easily digestible, and appropriate to the weakened digestive powers, is especially to be recom- mended, as well as the diligent administration of analeptics, 238 IMMERMANN.—SCURVY. especially of strong wine, cognac, or, if this be unattainable, of other alcoholic stimulants, and finally also of camphor and other direct stimulants, whenever paralysis of the heart is threatened. The administration of the preparations of iron and quinine, of which we have already spoken, is also generally very useful in the later stages of the disease. Lastly, a trip to the country, and the use of cold baths and similar invigorating measures are to be recommended during reconvalescence, to eradicate the last traces of weakness. Among the local symptoms of scurvy, the evffection of the gums in particular frequently calls for special local treatment. In combating this symptom, in addition to cleanliness and fre- quent rinsing out of the mouth with cold water or with water and vinegar, the local employment of astringents is to be recom- mended. In many cases great benefit has been derived from paint- ing the loosened, suffused, and inflamed gums with a solution of nitrate of silver, alum or tannin, with the tincture of catechu or ratanhia, or with a decoction of Peruvian oak or willow bark ; also from frequently touching the easily bleeding, super- ficial losses of substance, as well as the deeper ulcerations, with a solid stick of lunar caustic. Tincture of myrrh, spirits of cochlearia, borax, and chlorate of potassa have also not infre- quently been employed, locally, with good results in scorbutic stomatitis, and may therefore be briefly enumerated here in con- nection with the remedies just mentioned, as well as finally the mineral acids, in a sufficiently diluted form ; for instance, hydro- chloric acid (Cejka) in the form of an ointment, etc. It should also be recalled to memory here, that in many cases even the more intense forms of the scorbutic affection of the mouth have disappeared in a very short space of time, without any direct local treatment, but simply under the favorable influence of an appropriate treatment of the main disorder. This circumstance must not, however, lead us to neglect local treatment entirely. The attempt must be made to check, according to the ordi- nary rules, partly by local applications, partly by internal reme- dies, the hemorrhages which occur in various parts of the body during the course of the disease. In epistaxis, in order to pre- vent as much as possible the exhaustion of the patient, an early TREATMENT. 239 use of the tampon and the application of cold are advisable ; in hemorrhages from the stomach etnd bowels, the swallowing of pieces of ice or alum-whey, and the application of large bags of ice to the abdomen ; in hemorrhages from the urinary passages, the internal use of tannin which acts locally on these parts ; in bleeding from cutaneous ulcers, compression or ligature of the eroded vessels, as well as the application of the solution of the chloride of iron to the bleeding surfaces, and, if required, the actual cautery, etc. The acetate of lead and the ergot of rye given internally in large doses, deserve special mention, as rem- edies which, as a rule, possess great value without reference to the particular site of the hemorrhage. Of the affections of the skin in scurvy the simple interstitial hemorrhages and the petechia?, ecchymoses and vibices arising from them, and also the slighter forms of dermatitis, require no special treatment. The scorbutic ulcers were in former times very often treated locally with the same fresh vegetable reme- dies which are used with so much success internally in com- bating the general disease. In many cases it was claimed that local improvement (comp. the observations of Lind and Krebel touching this subject) resulted from the application of slices of lemon, carrot poultices, crushed herbs (cochlearia, sedum acre, etc.), or brewers' yeast to the ulcerated surfaces. In no one case, however, was satisfactory evidence adduced to show that the improved appearance of the ulcerated surface was due exclu- sively to these local applications, and not at all to the simulta- neous internal use of the same remedies. In recent times, apart from the energetic employment of the dietetic and medicinal measures directed against the general disorder, which constitute, at the same time, by far the most effectual treatment for all the localizations of the disease, the cutaneous ulcers receive only the usual surgical treatment of atonic ulcerations. This, as is well known, in addition to cleanliness and careful local disinfection, consists principally in the application of astringent or aromatic water dressings. The hemorrhagic inflammatory affections of the subcutaneous connective tissue, the periosteum, the bones, cartilage and articulations, which are met with in severe cases of scurvy must, like the cutaneous ulcers, be treated according 240 IMMERMANN.—SCURVY. to general surgical rules, since we do not as yet possess and probably never shall discover any effective local treatment spe- cially directed against the scorbutic nature of the troubles. At all events, the lotions and fomentations with water, diluted vinegar, spirits of camphor, and other aromatic and spirituous fluids, which have been recommended with this view, although they may have proved very beneficial in many cases, cannot be counted in the category of the special antiscorbutic local remedies. In the hemorrhagic infleimmedions of the serous membranes, especially of the pericardium and the pleura, if the exudation should become so extensive that life is directly endangered through the mechanical interference with the respiration and cir- culation, the removal by operation of the hemorrhagic fluid would certainly be indicated (of course with strict observance of the usual and necessary precautions). In consequence, however, of the very dangerous character of the operation of paracentesis, when performed on the pericardium, it should only be resorted to in cases of the most urgent necessity. In this respect scorbutic pericarditis presents the same indications as inflammation of the serous sac arising from other causes. The case is different in regard to the removal of pleuritic exudations. Here, on account of the trifling nature of the procedure, and the freedom from danger of the aspiration method, which has lately come into general use, the operation may very properly be resorted to as freely and as often as in the treatment of ordinaiy pleuritis. For the rest the same rule, which we have repeatedly mentioned as possessing a general application to the localizations of scurvy, applies with special force to the inflammations of the serous membranes, /. e., without appropriate treatment of the constitu- tional disorder in which they take their root, they do not show the slightest tendency to recovery, while, on the contrary, under a properly conducted general treatment, they often vanish as it were spontaneously and with astonishing rapidity, simulta- neously with the disappearance of the scorbutic cachexia. Hence, in the treatment of these inflammatory processes the greatest weight must, at all events, be laid upon the measures directed against the cachexia, and, if necessary, recourse may be TREATMENT. 241 had, with more or less hope of success, to special treatment, according to the ordinary principles of therapeutics. The same may be said of the treatment of the scorbutic affec- tions of the eye, for a detailed account of which we refer the reader to the text-books and the more extended works on oph- thalmology. With regard to the hemeralopia, which is quite frequently met with as a complication or sequel of scurvy, we have already mentioned in the section on complications, that it usually disappears simultaneously with the scurvy, when the dietetic treatment indicated for the latter is employed. We also stated that this peculiar behavior proves that there exists a pretty close, although not yet accurately definable, genetic con- nection between it and the scurvy. In regard to the treatment of other complications of scurvy we must refer in general to the appropriate chapters of this Cyclopaedia (see in particular Mala- rial Diseases, Dysentery, Syphilis). Before concluding, however, we must mention expressly that the existence of scurvy, with its pregnant symptoms of weakness and its hemorrhagic inflam- matory diathesis, necessitates the greatest prudence and care in the selection of the methods of treatment, and that this gen- eral disorder must often be overcome before the correct treat- ment of the complications can be entered upon with sufficient confidence. VOL. XVII.—16 Morbus maculosus Werlhofii. Syn.: Purpura hemorrhagica. P. G. Werlhofii opera 6mnia collegit et auxit J. E. Wichmann (Hanover, 1775). pp. 425, 540 et 748.— Ilarless, Hufeland's Journal. 1800. p. l.—J. E. Gauthier Bellafonds, Essai sur la maladie tachetee hemorrhagique de Werlhof, etc. Paris, 1811.—Rudolph, De morbo maculoso hsemorrhagico Werlhofii. Ber. 1811.— Wentzke, Do morbo maculoso Werlhofii. Diss, inaug. Ber. 1820.—Ilergt, Ueber Wcrlhof's Blutneckenkrankheiten. Leipzig, 1829.— Rayer, Hautkrankheiten tibersetzt von Stannius. 2. Aufl. (1839). Bd. III. S. Wi.—Krhonlein, Spec. Pa- thologic und Therapie (herausgegeben von seinen Zuhorern). Bd. II. S. 41 (1841).—Simeons, Heidelberger Annalen. Bd. II. 2. S. 979.— Wxuderlieh, Hand- buch der Pathologie und Therapie (1856). Bd. IV. S. 584.—Cooler, Deutsche Klinik (1862). 8. 9.—Chambers, Lancet T. 1.10. March, 1864.—Nysscus, Presse medicale. 1864. No. 4.—Reder (Hebra), in R. Virchow's Handbuch der spec. Pathologic und Therapie. Bd. III. 4. S. 719 ff. (1865).—Lcderer, Wiener med. Presse (1868). Bd. IX. S. 29.—Henoch, Berl. klinische Wochenschr. Bd. V. (1868) No. 50.—Halbermann, Beitrag zur Erkcnntniss der Purpura. Inaug. Diss. Bonn, 1869.— Dahlerup, Bibl. for Lager. 5 R. XX. p. 174.—Molliere, Recherche clinique sur la nosographie du purpura hemorrhagica, etc. Lyons, 1874.— Henoch, Berl. klin. Wochenschrift. Bd. XI. (1H71). Nr. rA.—^rheby- Buch, Deutsch. Arch. f. klin. Med. Bd. XIV. S. 466.—H. Bohlfs, Memorabilien. Bd. XX. S. 433. General Nature of the Disease. The names Purpura hannorrhagica and Morbus maculosus Werlhofii have, since the time of Werlhof, been applied to those very peculiar and rare cases of acquired and transitory hemor- rhagic diathesis, which, on account of their sporadic occurrence and their relatively brief duration, and moreovei- also on account of the obscurity of their etiology and the evpparent spontaneity of their development, cannot be classed under Hevme>philia, 244 IMMERMANN.—MORBUS MACULOSUS. Scurvy, or the ordinary symptomatic tendency to bleeding. With regard to the last it must be remembered, that the hemor- rhagic diathesis is frequently observed as a consecutive or accom- panying symptom of certain severe acute or chronic diseases, such as variola, typhus exanthematieus, phosphorus-poisoning, leukamiia, progressive pernicious anamiia, protracted icterus, etc. In such cases, however, since it has developed on the foundation furnished by another well-defined primary disease, it must be regarded and classed as purely symptomatic, so far as its clinical nature is concerned. Strictly speaking, the same is true also of the hemorrhagic diathesis of scurvy, for in that disease the tendency to hemorrhage is usually not observed until after the scorbutic general disturbance has set in, and, furthermore, the hemorrhages when they occur have in all probability a direct causal connection with the pre-existing cachexia. The cases designated as ''Morbus maculosus" differ from those of scurvy and from those of the ordinary symptomatic hemorrhagic diathe- sis in this, that the affection possesses more or less distinctly the character of an essential disease, that is to say, the tendency to hemorrhage, although sometimes very marked, cannot be sufficiently explained either by the anamnestic data or by the somatic conditions of the patients, and cannot be made more intelligible by analogy with other similar observations. As prototypes of the disease in question, we can therefore take only those cases in which the hemorrhagic diathesis is developed suddenly and unexpectedly at any period of life in individuals previously healthy, and in which it cannot be considered, as can many anomalous cases of haemophilia, as the result of an inher- ited predisposition. Less typical, and therefore in their clinical bearings the subject of much controversy, are : first, certain cases which differ in many cardinal points from the clinical pic- ture of scurvy, but, nevertheless, on account of the external conditions under which they develop, present a certain, although usually only an apparent etiological similarity with the latter disease; secondly, cases which occur in individuals still suffer- ing or recently recovered from some other disease, and which, although the connection is merely external and accidental, remind us of the symptomatic hemorrhagic diathesis from the DEFINITION OF THE DISEASE. 245 fact that the affected persons were not previously in perfect health; thirdly and lastly, those cases in which the hemorrhagic phenomena are decidedly the most prominent symptoms, but in which other pathologiced phenomena are also observed which cannot be regarded as directly and immediately dependent upon the hemorrhagic diathesis, or upon the hemorrhages that have taken place. We will presently discuss in detail the nature of the most frequent of the concomitant phenomena alluded to in this third category, and also the appropriateness, to these com- plicated cases, of the name given to the disease. It is necessary first to consider briefly the hemorrhagic diathesis, since it pre- sents itself in the individual cases of morbus maculosus under different forms and in varying degrees of intensity. These vari- ations are not, it is true, of essential importance, but they have led pathologists to constitute subdivisions of the disease with different names. Hebra, Reder, and other authors, denominate as "Purpura simplex" that simplest form of the disease which consists exclu- sively in the development of minute petechia, while throughout the whole course of the affection no extensive interstitial cuta- neous extravasations and no hemorrhages into other parts take place. If, on the contrary, in addition to these minute petechise, larger spots and even extensive ecchymoses and vibices appear upon the general surface, and if further, in addition to the skin, internal parts, such as the mucous and serous membranes, are attacked by the hemorrhagic diathesis, the same authors deno- minate the disease as "Purpura hemorrhagica." In many text-books the milder form of morbus maculosus, the purpura simplex, on account of the insignificance of its clinical and ana- tomical characters, is classed, not among the general hemor- rhagic diseases, but among the local affections of the skin. Experience teaches, however, that morbus maculosus very fre- quently begins as a so-called purpura simplex, which later develops into a purpura hemorrhagica, in consequence of the supervention of extensive cutaneous extravasations and internal hemorrhages. Hence, since it is impossible in any given case of purpura simplex to predict with certainty that it will run its whole course strictly as such, the systematic subdivision of the 24G IMMERMANN.—MORRIS MACULOSUS. disease into these two varieties must be regarded as purely con- ventional and artificial. We therefore prefer to treat of purpura simplex also among the general disturbances of nutrition. Like purpura haMiiorrliagica, it is in our opinion one of the forms in which AVerlhof s disease shows itself. It maybe defined as a mild and very rudimentary form of this pathological species, which may either remain in this embryonic stage until recovery sets in, or may at any moment be transformed into the severer form of the disease. In point of severity and development, purpura simplex and purpura hemorrhagica, therefore, are simply different grades of the same essential hemorrhagic disease. It must be well under- stood, however, that for the development of this disease, it is essential that there should be no other primary disturbances in the given cases. That, on the other hand, the secondary symp- toms, especially such as characterize general anemia, will not be wanting after the occurrence of profuse hemorrhages, is too self- evident a fact to require explanation, or consideration here. We must, however, investigate at this point the question whether we should or should not include under the head of morbus macu- losus, those cases of spontaneous hemorrhagic diathesis which present a somewhat more complicated clinical history. In this connection we must mention first, that, while many cases both of purpura simplex and purpura hemorrhagica run their course unaccompanied- by fever [purpura non febrilis), others, on the contrary, exhibit febrile movements {purpura febrilis) without there being any special reason, any apparent anatomical cause, for the elevation of temperature. The fever in these cases may occur only at the height of the disease, or at least not for a considerable time after the first extravasation of blood takes place, or it may actually precede and usher in the hemorrhagic symptoms. The cases belonging to the first variety can uncon- ditionally and unhesitatingly, for reasons yet to be given, be classed as morbus maculosus, but there is some reason to doubt the clinical connection of the cases which present a febrile pro- dromal stage, with ordinary purpura, and we do not believe that satisfactory proof of the identity of the two can be adduced. Notwithstanding this fact, however, we are compelled to con- DEFINITION OF THE DISEASE. 247 sider here also this second form of purpura febrilis, because it is scarcely possible to place it in any other part of the patholo- gical system, and because, moreover, not a few of these cases correspond, in every respect, with the exception of the fever, with those of purpura non febrilis. A somewhat greater varia- tion from the typical form of the latter affection is presented by certain cases in which either with or without a prodromal fever other more local disturbances precede for a short time the hemor- rhages, and frequently also persist as long as the latter. These local disturbances are often of a rheumatic character; they consist especially in pains or painful swellings of one or several joints. The question at once suggests itself, whether these cases of so-called p urpur a rheumatica are also to be classed as morbus maculosus or not'( On the authority of Schoenlein, who intro- duced it into pathology as a separate and special disease, the much spoken of peliosis rheumatica was for a long time believed to be a peculiar rheumatic-hemorrhagic affection entirely dis- tinct from the morbus maculosus Werlhofii. Under that name Schoenlein, as well as Fuchs, Canstatt, and others, understood a hemorrhagic disease, characterized by extravasations into the cutaneous layers alone without any internal hemorrhages; these extravasations are in the form of small petechie, but the affection is distinguished from purpura simplex by the fact that the bleeding is preceded by pain in the joints and frequently by fever. Although, as before remarked, the clinical picture thus produced has been generally regarded as a distinct and typical disease, or a pathological species sui generis, Scheby-Buch' has lately proved, by direct observations, the existence of transition cases between the so-called peliosis rheumatica and purpura hemorrhagica. He observed namely cases which began like peliosis, with fever, pain in the joints, and consecutive petechial exanthem, but subsequently exhibited, as in purpura hemor- rhagica, extensive extravasations into the skin and internal hemorrhages. It need scarcely be remarked that the occur- rence of these cases makes the existence of peliosis rheumatica, as an independent disease, very questionable. It appears to us, 1 Deutsches Archiv fiir klinische Medicin. Bd. XIV. S. 466. 248 IMMERMANN.—MORBUS MACULOSUS. therefore, advisable to discard peliosis rheumatica as a distinct disease from our nosology, and to employ for all the forms of essential hemorrhagic diatheses which commence or are accom- panied by rheumatic symptoms, the more general and less objectionable name of purpura rheumatica. We must, however, —and here we are in perfect accord with Scheby-Buch * and Sena- tors—insist explicitly on the non-identity of these cases with those rather infrequent cases of acute articular rheumatism, in which, in consequence of the development of an endocarditis ulcerosa, and the resulting embolism, multiple extravasations are produced. It is, at all events, very noteworthy that purpura rheumatica never develops into severe articular rheumatism ; that, further, the profuse sweats so constantly present in the latter are entirely wanting in the former disease; and finally, that it has no tendency to be complicated with endocarditis. It is evident from these facts that purpura rheumatica is not a special form of acute rheumatism, and hence it cannot correctly be designated by such names as Rheumatismus petechialis, Rheumatismus hemorrhagicus, etc. On the contrary, it is probably more correct to assume, with Scheby-Buch, that the rheumatoid articular affections in the cases in question are dependent upon the hemorrhagic diathesis, with which they possess some close causal relation. Upon this assumption, which cannot, however, as yet be positively proved, we regard purpura rheumatica as a sub-variety of morbus maculosus. In what follows we will, therefore, study it in connection with the ordi- nary, non-rheumatic form of the disease. Finally we will have to call attention, when considering the symptoms of morbus maculosus, to the occurrence, in certain cases, of severe gastric disturbances which complicate still further the clinical history of the disease (Henoch, Scheby-Buch). In our opinion, however, it is not difficult to furnish good evidence to prove that such cases do not form an independent pathological class, but that they belong properly in the general family of the essential hemorrhagic diathesis (morbus maculosus). 11. c. S. 528. * Vol. XVI. of this Cyclopasdia. ETIOLOGY. 249 Etiology. Cases of hemorrhagic diathesis which, in accordance with their clinical history, must be classed as morbus maculosus Werlhofii, occur at all periods of life, in both sexes and in every possible form of physiological constitution. Still, it would appear from the literature of the subject (H. Marsh, Churchill, Stokes, Hunt, Law, Rilliet and Barthez, and others), that the predisposition to the affection is relatively greatest during the period of adolescence, namely, from the fifteenth to the twentieth year of life. According to Curran, the female sex is in general somewhat more disposed to it than the male. Strong and ple- thoric individuals cannot by any means be said to possess an immunity from the disease, since in quite a number of the cases that have been observed, the patients were previously perfectly healthy and robust in every respect. Still, the majority of the cases have occurred in subjects of a weak and anemic constitu- tion ; it must be distinctly stated, however, that, at the time of the outbreak of the hemorrhagic diathesis, none of the cases reported by us and others were suffering from the extreme forms of progressive pernicious anemia. (AVith reference to this subject see Vol. XVI.) No inherited predisposition to the diathesis can be demonstrated in any way ; on the contrary, the sporadic character in respect of both time and place, as well as the transitory nature of the disturbances, is highly characteristic of morbus maculosus. Observations have been recorded, however, which prove that the disease can occur in the same individuals at longer or shorter intervals, and hence demonstrate the exist- ence in certain persons of an evident individual predisposition to the disease. We are still entirely ignorant of the nature of this predisposition, but it probably depends upon congenital peculi- arities. It would not be justifiable to classify such cases at once as hemophilia, since not only the facts that the affection has not been inherited from the parents, and can not be transmitted to the offspring, but also the fact that during the intervals the patients enjoy entire immunity from the hemorrhagic tendencies, prove that we have to deal with a very different affection. 2oO IMMKRMANN.—MORBUS MACULOSUS. Finally, in connection with the individual predisposition to morbus maculosus we must also mention here the occurrence of the affection in convalescents from all sorts of severe diseases, for instance, typhoid fever, and other exhausting processes. Here the persons affected can by no means be said to be healthy, in the ordinary sense of tin? word, but still less can they be said to be actually sick, and hence the developing hemorrhagic diathesis cannot be properly regarded as symptomatic. Person- ally we have been led by a number of observations made by ourselves, to believe that the predisposition of convalescents to morbus maculosus is greatest exactly at that period of the pro- gressing recovery when the pallor and weakness are fast disap- pearing, when they make their first attempts to walk, and when the returning appetite demands an increased supply of food ; at a time, consequently, when they cannot longer be said to be "•sick" in the usually accepted sense of the word. We intend, when considering the essential character and the pathogenesis of the disease, to return again to these cases of morbus maculosus, and we will then state more definitely our views respecting their possible mode of occurrence. Very little is known concerning the determining causes of morbus maculosus. In very many of the cases the disease is developed, to all appearances, spontaneously, and affects persons whose bodily health and hygienic surroundings have previously been excellent. In other cases, it is true, the patients had pre- viously been in needy circumstances, lived in unhealthy houses or on insufficient food, etc., but still, it would be improper to lay too much stress, in the etiology of the disease, upon these points, since countless individuals are constantly sub- jected to such influences, while the disease in question is essentially rare. In other words, we cannot subscribe to the hypothesis which makes morbus maculosus actually nothing more than a mild form of scurvy. The non-identity of the two processes is demonstrated not only by important differences in the manner in which they begin, and the course which they run, and by not less striking differences in the symptomatology, but more clearly still by the simple fact, that a cumulative out- break of that form of the hemorrhagic diathesis, which, by rea- GENERAL FEATURES OF THE DISEASE. 251 son of its clinical characters, must be designated not as scurvy, but as morbus mxteulosus, has never yet been observed in communities where all are living under the same hygienic sur- roundings. On the contrary, morbus maculosus always occurs sporadically, while scurvy generally prevails as an epidemic. A peculiar nomenclature, which is entirely incorrect and inde- fensible, has been based on the supposed identity of the two morbid processes ; according to it, morbus maculosus figures in many text-books as " Land-scurvy;' just as if the severe form of scurvy, in its more restricted sense, could occur only at sea, and has not appeared sufficiently often on land. It is evident, from the foregoing, that the etiology of morbus maculosus, both as regards the nature of the individual predis- position, and the determining causes, is still involved in almost complete obscurity. We may even assert, and this is a point which may prove of diagnostic importance, that the less we can discover and'positively affirm concerning the etiology of a case of transitory hemorrhagic diathesis, the greater is the probability that it belongs in the category of morbus maculosus. Pathology. • General Feed arcs of the Disease. Morbus maculosus often begins acutely and at the same time in a very characteristic manner. In such cases there are no pro- dromal warnings, such as local disturbances or a general state of ill-health, the first indication of the existence of the hemorrhagic diathesis being the appearance of petechie upon the skin or the occurrence of some other hemorrhagic symptom, ex. gr., epis- taxis. Besides these specially pure and typical forms of the dis- ease, there occur others in which the hemorrhagic symptoms are preceded for several days by mild prodromal symptoms of an undecided character, such as slight languor, headache, loss of appetite, and sometimes even moderate fever. These prodromi usually last only one or two days, rarely longer than a week. .1 ■marked initial cachexia, like that which so generally precedes 252 IMMERMANN.—MORBUS MACULOSUS. scurvy, is never observed. Finally, some cases begin with rheu- matic symptoms, and to such the names Purpura rheumatica or Peliosis rheumatica have been applied. Painful sensations are experienced in certain joints, particularlj- in those of the lower extremities (the knees and ankles). These pains may, or may not, be accompanied by slight fever. They continue several days, and are sometimes attended by slight swelling of the joints. The exanthem then appears, and simultaneously with its devel- opment the articular affection, as a rule, abates. The development and extension of the cutaneous hemorrheiges are always painless, and are not preceded by any hyperemic redness of the skin. The extravasations often cover the entire body. It has been said that the skin of the face is not at all, or at least very rarely, affected in morbus maculosus. We cannot agree with this statement, since in several cases we have seen not only petechie, but even extensive ecchymoses, which were unquestionably not of traumatic origin, upon the face, and especially on the upper eyelids and the margins of the orbits. The hemorrhagic exanthem, however, is usually most abundant on the lower extremities, and next to them on the trunk. On the latter, in the severer forms of the affection, the number of purpura spots may amount to many hundreds. In some, but not in all of the cases designated as peliosis rheumatica, it has been observed that the petechie appeared first in the neighborhood of the painful joints, and spread gradually from them to more dis- tant parts of the body. The individual spots vary greatly in size, ranging generally from that of a large pin-head to that of a lentil, a pea, or a bean. The larger ecchymoses and vibices (compare the preced- ing chapters on Hemophilia and Scurvy) are much less fre- quent than the smaller spots, but they occur here and there upon the surface in nearly every decided case of purpura hemor- rhagica. In shape the smaller spots are often, and perhaps gene- rally, round, but star-shaped and irregular spots are not at all rare among them. The larger ecchymoses assume every possible form. The hemorrhages are not so exclusively confined to the regions of the capillary network of the hair follicles as is the case in the other petechial exanthemata. We find, it is true, GENERAL FEATURES OF THE DISEASE. 253 numerous petechie which are pierced through the centre by a hair, but we usually find many spots, both small and large, which do not present this peculiarity. Finally, in morbus maculosus, as well as in scurvy, we find, in addition to the macula, more or less numerous vesicles, which are evidently produced by circumscribed hemorrhages into the rete Malpighi from the capillary loops of the papille of the skin. The color of the fresh spots is the same as in other hemor- rhagic efflorescences—namely, a dark bluish-red. It does not alter on pressure, but as time passes on it changes successively to greenish-blue, brown, and yellow (compare the descriptions of Scurvy and Hemophilia). It is exceedingly common for fresh, crops of the petechial eruption to appear at varying inter- vals during the course of the disease. When several such relapses have occurred, the body of the patient presents a very odd appearance, since the spots, which vary greatly not only in size and shape, but also, owing to their different ages, in« color, are scattered about in a most irregular manner. With regard to these relapses we must also mention that, like the first outbreak of the exanthema, they are frequently ushered in by slight fever and pains in the joints. Sometimes the process described above is repeated several times, with great exactitude, each fresh outbreak of the eruption being attended by a modifi- cation of the premonitory symptoms. In other cases, on the contrary, there is no concurrence in point of time between the intercurrent development of fresh elevations of temperature and articular pains on the one hand, and of fresh cutaneous hemor- rhages on the other, the relations of these different symptoms to one another being very irregular. The occurrence of the majority of these relapses of the hemor- rhagic exanthema does not, by any means, seem to be depen- dent upon special external causes ; like the hemorrhagic dia- thesis in general, they are apparently perfectly spontaneous. Still, in many cases they are dependent upon some mechanical injury, or upon some change in the functional activity of the heart, etc. Just as in scurvy, we find that suggilations appear at points where the skin has been subjected perhaps accident- ally to unusual pressure or to some other slight injury, or a 2.")4 IMMERMANN.—MORBUS MACULOSUS. relapse of the purpura eruption occurs, and a fresh crop of spots appears particularly on the lower extremities, when the patient makes some active movement—for instance, when after having been confined to bed for some time, he makes his first attempt to get up and walk about. In many, but by no means in the majority of the cases, the hemorrhagic diathesis manifests itself clinically only by the eruptions on the external surface (purpura simplex). It is far more frequently attended also by hemorrhages in other parts (purpura hemorrhagica proprie sic dicta). These may happen at any time during the course of the disease, even at its very beginning. There is also a class of intermediate cases in which the visible mucous membranes, viz., those of the mouth, pharynx, and eyes, exhibit more or less extensive interstitial extravasa- tions, without any free hemorrhage from their surface. Generally, however, the symptoms of the hemorrhagic dia- thesis are not so limited, the interstitial extravasations being accompanied, as a rule, by more or less copious, superficial hemorrhages. Profuse and exhausting hemorrhages from the superficial and deep mucous membranes, namely, from the nose, stomach, intestines, urinary passages, genitals in women, and bronchi, are much more common in morbus maculosus than even in severe cetses of scurvy. Hemorrhages from the mucous lining of the mouth, and particularly the gums, also occur, but the bluish-red discoloration, the softening, swelling and spongy char- acter of the gums, as well as the excessive sensitiveness of these parts which is very generally present in even the mildest cases of scurvy, are entirely wanting. If we examine the gums after removing the coagulated blood, which frequently covers them, we will find them,even in cases where no teeth have been lost, either perfectly normal in color and consistency, or oftener still somewhat pale and bloodless, but never bluish-red or swelled. In morbus maculosus consequently all the signs of a hemorrhagic inflammation of the gums are wanting. This fact will be found to possess considerable diagnostic importance. In Werlhof s disease hemorrhages also occasionally occur within the serous cavities, viz., the pleura, the pericardium, and the peritoneum, and also in the meninges and, in the substetuce GENERAL FEATURES OF THE DISEASE. 255 of the brain} They take the usual course of such accidents, generally ending fatally. These complications are, however, decidedly exceptional, as is also the formation of extensive he- matomata in the subcutaneous connective tissue. A participa- tion of the muscles in the hemorrhagic accidents has occasionally been observed, but it is by no means common. The hemorrhagic symptoms on the part of the skin and mucous membranes constitute consequently the most important and essential part of the clinical picture of morbus maculosus. We may in this place expressly state it as a fact that in many cases of the disease there are absolutely no other symptoms, either local or general, of illness. When, for instance, the dis- ease affects persons previously strong and healthy, and is not accompanied by fever or rheumatic affections of the joints, and when, further, the surface hemorrhages from the mucous mem- branes are not too frequent or abundant, the general health of the patients may be almost unaffected throughout the entire course of the disease. This state of subjective good health then presents a striking contrast to the objective appearances. When, on the contrary, the hemorrhages are often repeated and copious, and especially if the patients were previously anemic, we can- not wonder at the consecutive appearance of symptoms showing an alarming degree of anemia: for instance, pallor, dropsical swellings, extreme weakness, fainting fits, etc. Nor is it sur- prising that in many of these cases death should occur under the symptoms of acute oligemia. Still, although the condition of the patients is often alarming, a fatal termination is in general not very frequent. The sickness ends by far more frequently in recovery after the expiration of one or two weeks. In other cases the disease is more protracted because of the repeated recurrence of the hemorrhages now in one form, now in an- other ; it is only when they have finally ceased that improve- ment sets in, and the pale and exhausted patients gradually re- gain strength and health. Certain authors, particularly Henoch,2 have reported cases 1 Tardieu, L'Union. 1870. No. 48. 2 Berl. klin. Wochenschr. 1K5S. Nr. 50: ferner, 1S74. Nr. 51. 2.36 IMMERMANN.—MORBUS MACULOSUS. which differed somewhat in their course from those above de- scribed. These cases presented a peculiar, more or less idio- pathic diathesis of a transitory character, but in addition to the fever and purpura, and also to marked articular affections, which, however, were not present in all of them, they exhibited severe gastric and intestinal symptoms. These consisted chiefly in vomiting of bilious matters, meteorismus and tenderness of the abdomen, and severe colicky pains ; they recurred several times during the course of the disease. Although the recurrence of these symptoms is not mentioned in other treatises on the dis- ease, we cannot understand why Henoch should be inclined to regard such cases as constituting a special form of disease, entirely distinct from morbus maculosus. We believe, with Scheby-Buch,' that the explanation of such cases lies in the as- sumption that the digestive apparatus is involved in the hemor- rhagic process, that we have to deal probably with hemorrhages in the serous coat of the stomach and intestines. Post-JIortem Appearances. When death occurs in the course of morbus maculosus it is almost invariably, as far as we yet know, the result of too fre- quent and copious hemorrhages. The dead body is exceedingly pale in consequence of the loss of blood ; it is frequently some- what cedematous, and is usually covered with numerous pete- chial spots, both old and recent, large and small. The condition of the general nutrition depends upon the duration of the disease; in the cases which prove rapidly fatal it is in general unaltered, but in those which have run a protracted course it is somewhat impaired. All the internal parts, like the skin, present an ane- mic appearance, on account of the diminution in the quantity of blood contained in them. The mucous membrane of the lips, tongue, gums, hard and soft palate and pharynx is usually covered with blackish, half-dried blood crusts. Upon removing these the membrane sometimes appears pale but otherwise nor- mal, sometimes presents superficial erosions, and, finally, is some- 11. c. S. 490. POST-MORTEM APPEARANCES. 257 times more or less thickly covered with small ecchymoses. Similar erosions and ecchymoses are also met with, often in immense numbers and spread over a very large space, on the mucous membranes of the stomach, intestines, the pelvis of; the kidneys, the ureters, the bladder, the female genitals, etc. They are less frequent upon the mucous surfaces of the air-pas- sages. The contents of the stomach and intestines are often mixed with large quantities of loosely coagulated or still fluid blood. The bronchi contain bloody mucus and sometimes freshly exuded blood in considerable quantities. Occasionally, but not often, blood is found in the pericardial, pleural, and peritoneal cavities. Multiple interstitial extravasations in the tissue of the serose, and small collections of blood in the subserous connective tissue, are much more common. In other respects the tissues of the pericardium, pleura, and peritoneum in such cases are approximately normal or merely somewhat hyperemic. The extensive, fibrinous exudations on the surface and the other macroscopic inflammatory changes, which are so common in the fatal cases of scurvy in which these membranes have been in- volved, are wanting in morbus maculosus. Very little is known of any other constant anatomical changes. We have no exact data respecting the appearances of the articular cavities and ligaments in the cases which were com- plicated during life by rheumatic symptoms. On this subject there exists only a single publication which emanates from Traube's clinic. The case was one of "peliosis rheumatica," in which, post-mortem, the synovial membranes of the affected joints were found somewhat injected, and the quantity of the slightly clouded synovial fluid somewhat increased (Leutholdt1). Of the condition of the walls of the vessels, particularly of the capil- laries, we are also almost entirely ignorant.2 It is very probable, however, that in these cases, just as in other fatal cases of ane- mia due to excessive loss of blood, a fatty degeneration of the vascular tissues and of the muscles of the heart has taken place. 1 Berl. klin. Wochenschrift. 1865. No. 40. 2 In one case Vi'ilmn discovered amyloid degeneration of some of the capillaries in the immediate neighborhood of a few of the petechia. Brit, and Foreign Med. and Chirurg. Review. 1850. Oct. p. 480. VOL. XVII.—17 258 IMMERMANN.—MORBUS MACULOSUS. In a majority of the autopsies the heart has been found relaxed and its muscular substance pale. The valves, as far as is known, were perfectly normal, apart from some unimportant changes, and the cavities of the organ, in correspondence with the general anemic condition, contained very small quantities of loosely coagulated blood. Very few reports of the condition of the blood during life have been published, and even they are in many points at vari- ance with one another. Its color is said to be usually rather dark in recent cases ; in older cases, on the contraiy, especi- ally when copious hemorrhages have occurred, it is bright. A genuine oligocythemia, therefore, does not appear to exist pri- marily in morbus maculosus ; when it occurs it is developed at a later period, and is due to the hemorrhages (for an example of the reverse see Progressive Pernicious Anemia). In a case recently observed by us in the clinic at Basel, which was very severe, but nevertheless terminated in complete recovery, the relative proportions of the red and white blood-corpuscles to one another was perfectly normal during the first days of the disease, but subsequently the white corpuscles slightly exceeded the red in number. This condition, however, could be regarded only as an instance of that form of moderate leucocytosis which is known to be a regular result of copious hemorrhages. In the case referred to, the color of the blood corresponded with its microscopic appearances ; it was at first perfectly normal, but afterwards became somewhat paler. Its coagulability was not affected. Albers' experience in this last respect agrees with ours : he states that the blood of persons suffering from purpura hemorrhagica does not lose its capacity for coagulation. Other observers, however, particularly Legrand, Rayer, Biett, and Bec- querel, state that they have found the blood very little or even not at all coagulable. Of the quantitative relations of the solid constituents of the plasma to one another, nothing is at present definitely known, nor do we know whether or not any abnormal substances are present in the blood. The spleen and lymph glands present no constant changes. The first-named organ, however, has repeatedly been found enlarged, and its pulp was then of a pasty consistency (Bill- ANALYSIS OF THE SYMPTOMS. 259 roth,1 and others). In a case examined by Ponfick,2 the medulla of the bones in various parts of the skeleton was found to contain numerous large and small hemorrhages. Special Symptomatology. Analysis of the Pathological Symptoms and of the Anatomical Appearances. The pathological symptoms of morbus maculosus which we have described above, may be divided according to their nature into four classes. It must be admitted, however, that they are not present with equal completeness, or in the same grouping and combination in all cases. The first, and under all circum- stances the most important of these classes, is constituted by the hemorrhagic symptoms, which are characteristic of the affection, and without which the existence of the disease is un- imaginable. The second class includes the febrile symptoms, which either precede the hemorrhages or are developed inter-cur- rently. They are, however, not unfrequently entirely wanting. Still less uniformly present, either as precursors or attendants of the hemorrhages, are the symptoms included in the third class, viz., the rheumatic pains and swellings of the joints, which are observed in the cases described as purpura (peliosis) rheu- matica. We have seen that these symrjtoms sometimes do and sometimes do not possess a definite connection with the fever, and also that they may accompany the hemorrhagic accidents even when fever is entirely wanting. Finally, the fourth class comprises those severe gastric and intestinal symptoms which are met with in a few cases, and of which we spoke at the close of the section on general symptomatology. The cutaneous hemorrhages as well as those of interned. parts in morbus maculosus are in general simp>le extravasations, that is, they are not dependent on any intense local hyperemia or inflammation. That the cutaneous and other hemorrhages are not due to inflammation is evident both from the fact that 1 Virchow's Archiv. Bd. XXIII. S. 405. 2 Ibidem. Bd. LVI. 4. S. odi (1873). 260 IMMERMANN.—MORBUS MACULOSUS. the cutaneous petechie and ecchymoses are not preceded by any roseolar or erythematous rash, and from the anatomical lesions in the internal viscera which were the seat of hemorrhages intra vitam. In morbus maculosus, therefore, one may properly speak of the existence of a hemorrhagic, but not, as in scurvy, of a concomitant inflammatory diathesis. In the development of the overwhelming majority of the individual hemorrhagic foci and free hemorrhages which occur in morbus maculosus, neither external mechanical injuries nor increased force of the heart's action can be said to have a causative influence. On the contrary, their origin is apparently spontaneous. Hence, it is necessary to seek for the immediate cause of these foci and free hemor- rhages, in some diseased condition of the walls of the capillaries, in consequence of which they are more easily ruptured, or at least become more permeable to their fluid and solid contents. These supposed structural changes in the capillary walls, how- ever, must be of the most delicate and imperceptible kind, since pathological anatomists are as yet entirely unable to give us a description of them. Some further remarks upon this subject will be found in the section on the "Nature and Pathogenesis of the Disease." The analysis of the febrile symptoms in morbus maculosas' furnishes support for the opinion that the fever, when present, is not always due to the same cause, and has not always the same clinical significance. The genesis of the fever is naturally most inexplicable in those cases in which the abnormal elevation of temperature precedes the hemorrhages, and is not accompa- nied by any other abnormal phenomena, such as the articular symptoms. Here there are no anatomical changes which could account for the occurrence of the fever, and hence we must, for the present, relinquish all hope of explaining it. The case is not much better with regard to that fever, which in connection with articular pains not unfrequently ushers in the cases of so-called purpura (or peliosis) rheumatica, since, to us at least, it does not seem by any means certain or even probable that this fever is directly dependent upon and symptomatic of the affection of the joints. These cases may be contrasted, on the one hand, with others in which the same articular pains and swellings ANALYSIS OF THE SYMPTOMS. 261 without fever initiate the disease, and on the other hand, clinical experience has taught us that an initial fever may exist without articular symptoms. It is easier to explain the occurrence of fever during the course of the disease, at a time consequently when numerous hemorrhages have already taken place, and collections of extravasated blood have formed at various places throughout the body. In these cases, just as in analogous cases in other diseases, there is reason to suppose that many of the febrile movements are of a resorptive nature, being symptomatic of the process of involution which is taking place in the collec- tions of effused blood; furthermore, that the blood, which has been extravasated into the interstices of the tissues, may some- times act as an inflammatory irritant on the surrounding parts. and thus cause slight fever. Finally, however, there is another possible and very different mode, in which the feVer may arise in some cases, namely, the one which we have chosen as the most probable one for the fever of progressive pernicious anemia (comp. Vol. XVI.). It will be remembered that, in the place referred to, we expressed our belief in the opinion that there exists a special "anemic fever," or that a predisposition to febrile movements accompanies the more intense grades of ane- mia, and is the immediate result of the excessive poverty of the blood. To save repetition, we will refer the reader to that article for the proofs that have been adduced in support of this hypothesis. Here we must point out, however, that the excessive losses of blood in severe cases of morbus maculosus may produce in a short time as extreme degrees of anemia as are met with in the latter stages of progressive pernicious anemia; and that con- sequently a fever which appears during the course of the former disease, at a time when the poverty of the blood is greatest, and which decreases and disappears coincidently with the anemia, may with perfect propriety be called an "anemic fever" in the sense in which we have used that phrase. That there are cases of febrile morbus maculosus in which the elevations of tempera- ture actually present a remarkable parallelism with the grade of the existing anemia, is clearty demonstrated by the case already referred to, which we ourselves observed in the clinic at Basel. 262 IMMERMANN.—MORBUS MACULOSUS. The following notes of the history of this case are taken from the clinical journal. A. S., sixteen and a half years old, photographer, born in Schleswig-Holstein. His father died recently of phthisis pulmonum et laryngis, and he has lived since with his mother and five brothers and sisters in needy circumstances; states, how- ever, that he was perfectly well until the day before his admission. An inherited or individual predisposition to hemorrhage does not exist. None of the other members of the family have at any time been subject to bleeding, and he states that they are all perfectly healthy. He himself never before suffered from hemor- rhagic accidents, and his present sickness came on suddenly and without warning. On the 12th of March, without any apparent cause, and when he Avas feeling in every respect entirely well, a hemorrhage from his tongue took place. On the following morning the patient noticed several bluish-red spots on his lips, and by noon his entire body was covered with numerous blood-spots of various sizes. Meanwhile his appetite was entirely unaffected, and he had no headache, no pains in the limbs or joints, and in short no subjective disturbances whatever. He was received into the medical clinic on March 14, 1876. Status prmsens: Moderately strong individual, of rather pale complexion. Petechise scattered over the face; on the upper and inner margin of the orbit on the left side, a large violet-blue ecchymosis. Exceedingly abundant petechial exanthem on the body and also on all the extremities. The lips and gums covered with blood-crusts. Upon removing them the gums appeared superficially excoriated in many places, but otherwise normal, except that they were somewhat pale. On the lips a few bluish-red spots about as large as a lentil, and on the dorsum of the tongue three bullae about 0.5 centimetre in diameter, filled with blood. The nos- trils on both sides obstructed with dried blood. No abnormities of the heart, lungs, liver, or spleen. Pulse moderately strong and regular, 74. Eighteen respi- rations per minute. March 14. Temperature: Morning, 98.6' F. Evening, 98.2° F. Further course: March 15. Temperature: Morning, 98.6° F. Evening, 100.4° F. During the day new petechia), epistaxis. The ophthalmoscopic examination of both eyes revealed no hemorrhages in the retina. The microscopic examination of the normally colored blood showed no increase in the relative number of the white blood-corpuscles. March 16. Temperature: Morning, 98.2° F. Evening, 100° F. Small ecchymoses in the conjunctiva. Upon the body, besides new petechise, several large, irregularly shaped ecchymoses. Gums not spongy, pale. Very dark, bloody urine was passed several times during the day. General health wholly unaffected. Appetite good. Countenance rather pale. March 17. Temperature: Morning, 98.7° F. Evening, 98.° F. Urine continues bloody. Two bloody stools. The older petechise already greenish ANALYSIS OF THE SYMPTOMS. 263 and brownish in color. New petechise. Towards evening, epistaxis, which was repeated in the night. March 18. Temperature: Morning, 98.7° F. Evening, 102° F. Recurring epistaxis so severe as to render plugging of the anterior and posterior nares on both sides necessary. Persistent hematuria and several bloody stools during the day. The patient feels languid, and is very pale. Pulse small, somewhat tense, 84. Respiration regular, and not accelerated. Spleen not enlarged. From this time, the temperature in the axilla was taken every two hcurs. Evening, 7 o'clock, 102° F.; 9 o'clock, 100.5° F.; 11 o'clock, 100.4° F. March 19. 1a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 11a.m. T. 100.4° 100.4° 100.5° 99.° 100.4° 100.7° 1p.m. 3 p.m. 5 p.m. 7 p.m. 8 p.m. 9 p.m. 11p.m. T. 101.6° 101.1° 102.6° 102.2° Soda? sal.1 gr. 56 99.5° 98.7° During the day the blood trickled from the nostrils through the tampon. Bloody urine and stool. Great weakness and pallor. March 20. 1a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 11a.m. T. 97.7° 99.5° 99.7° 102.2° 102.6° 101.8° 1p.m. 3 p.m. 5 p.m. 7 p.m. 8 p.m. 9 p.m. 11p.m. T. 101.1° 103.1° 103.1° 103.3° Sod. sal. gr. 84. 101.1° 96.8° Delirium. Spleen not enlarged. Urine no longer bloody. No stool. Extreme pallor. March 21. 1 a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 11 a.m. T. 100.4° 97.3° 96.6° 98.2° 98.2° 99.5° 1 p.m. 3 p.m. 5 p.m. 7 p.m. 8 p.m. 9 p.m. 11p.m. T. 100.4° 100.7° 103.5° 102.6° Sod. sal. gr. 84 101.3° 99.5° Tampon removed. No new cutaneous hemorrhages. Urine free from blood. No stool. March 22. 1a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 11a.m. T. 99.5° 100.° 99.5° 100.4° 101.3° 100.9° 1 p.m. 3 p.m. 5 p.m. 6 p.m. 7 p.m. 9 p.m. 11p.m. T. 100.9° 102.7° 103.1° Bath. 99.5° 102.2° 101.3° Urine and stool free from blood. Delirium. Prostration. March 23. 1a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 10 a.m. 11a.m. T. 102.2° 101.5° 101.3° 103.1° 103.1° Sod. sal. gr. 84 101.6° 1 p.m. 3 p.m. 5 p.m. 7 p.m. 9 p.m. 11p.m. T. 101.3° Bath. 99.5° 100.9 102.6° Bath. 103.6° Bath. 101-8° No new hemorrhages. Condition unchanged. March 24. 1 a.m. 3 a.m. 5 a.m. 7 a.m. 9 a.m. 11a.m. T. 101.3° 97.7° 100° 100.4° 100.4° 101.6° 1pm. 3 p.m. 5 p.m. 7 p.m. 9 p.m. 11p.m. T. 102.2° Sod. sal. gr. 84. 100.7° 100.4° 100.4° 99.5° 100.4° Sensorium not yet quite free. Great pallor. 1 Salicylate of soda. 264 IMMERMANN.—MORBUS MACULOSUS. March 25. 1 a.m. T. 99.9° 3 a.m. 97.7° 5 A.M. 99.3° 7 A.M. 100.° 9 A.M. 100.7° 11 A.M. 100.7° 1 P.M. 3 P.M. 5 P.M. 7 P.M. 9 P. M. 11 P.M. T. 101.6° Sod. sal. gr. 84. 101.3° 100.4° 98.7° 96.8° 99.2° March 26. 1a.m. T. 99.5° 3 A.M. 99.2° 5 A.M. 100.4° 7 A.M. 100.4° 9 A.M. 100.7° 11 A.M. 100.7° 1 P.M. 3 P.M. 5 P.M. 7 P.M. 9 P.M. 11 P.M. T. 101.5° Sod. sal. gr. 84. 100.4° 99.5° 98.7° 98.7° 98.7° Petechise faded. No hemorrhages. Spleen not enlarged. March 27. 1 a.m. T. 99.° 3 A.M. 98.4° 5 A.M. 99.2° 7 A.M. 103° 9 A.M. 101.1 11 A.M. 101.5° 1 P.M. 3 P.M. 5 P.M. 7 P.M. 9 P. M. 11 P.M. T. 102.6C 102.9° 103.1° 101.6° 101.6° 100.7° March 28. 1 a.m. T. 99.5° 3 a.m. 99.5° 5 A.M. 99.° 7 A.M. 99.° 9 A.M. 99.3° 11 A.M. 99.3° 1 P.M. 3 P.M. 5 P.M. 7 P.M. 9 P.M. 11 P.M. T. 99.9 100° 100.7° 100.7° 100.4° 98.7° From this on time there was no fever. The appearance of the patient improved. Sensorium became absolutely clear. So long as the hemorrhages persisted, the treatment consisted in the subcutaneous injection of ergotin, and the internal use of acetate of lead and ice. Appropriate dietetic rules were enjoined, viz., rest, the horizontal position, and for nourishment nothing but cold milk. The use of the preparations of iron was begun on the 29th of May. Rapid improvement in strength and appearance. He was discharged cured on the 4th of April. The rheumatic symptoms in the joints, which distinguish the cases of so-called Purpura rheumatica from other cases of morbus maculosus, form, in respect both to their genesis and to their anatomical nature, an exceedingly obscure chapter in the symptomatology of the disease. In no cases are there any gross nutritive changes in the joints which can give rise to them, and it is doubtful even whether these disturbances can properly be called inflammatory. Bohn l and others think they are due to collateral hyperemia and oedema, caused by embolism of small vessels in the neighborhood of the affected joints. We do not agree with them, since as yet neither the source of the emboli nor the emboli themselves have been demonstrated, and in the majority of the cases belonging in this category it would cer- tainly be impossible to demonstrate either. It is more probable that the same structural changes in the walls of the vessels ' Journal fiir Kinderheilkunde. N. F. Bd. I. S. 391. NATURE AND PATHOGENESIS. 265 which are at the bottom of the disease, and which at a later period facilitate the escape of the red blood-corpuscles, and thus produce the hemorrhagic accidents, are favorable at an earlier period to the percolation of large quantities of liquor sanguinis, through the capillary walls of the most various vascular prov- inces in the body, and that in this way transudations take place into the cavities of the joints. When these transudations are but small in quantity, they manifest themselves only by pains, but when they are more abundant they also cause swelling. Finally, we have already stated that purpura rheumatica cannot be regarded as a hemorrhagic form of ordinary articular rheuma- tism, and have briefly detailed the reasons which militate against such a supposition. With respect to the gastro-intestinal symptoms that are observed in many cases, we may repeat that we agree perfectly with Scheby-Buch, who regards the bilious vomiting, the meteor- ismus and tenderness of the abdomen, and also the severe colicky pains, as in all probability the direct consequences of the peri- toneal irritation caused by hemorrhages into the serous coat of the stomach and intestines. These symptoms might also possibly be in part due to extensive hemorrhagic infiltrations in the mu- cous coat of the digestive tract. Infiltrations of smaller extent have relatively often been found in this membrane at the autop- sies of purpura patients. Nature and Pathogenesis of the Disease. The analysis of the etiological and clinico-anatomical data shows that in morbus maculosus or purpura hemorrhagica (in- cluding the various symptomatological sub-varieties of purpura which we have here treated collectively), there exists a tretnsitory hemorrhagic diathesis, which possesses, much more than other intercurrent dispositions to hemorrhage, the character of an independent, or, as we have already expressed it, of an essential disease. For, although, as we have shown, the tendency to extravasation is sometimes exceedingly decided and general, it is at the same time in the majority of the cases so independent of all other pathological complications, and so isolated in a 266 IMMERMANN.—MORBUS MACULOSUS. manner as a temporary abnormity of the affected individuals, that in contrast with it all other forms of the transitory hem- orrhagic diathesis, and particularly the scorbutic, must be re- garded as relatively very imperfect examples of this pathological species. It is evident, a priori, that the primary cause of this transitory, and at the same time so independent morbid disposi- tion to extravasations from the vessels, can lie only in a disturb- ance of the physiological relations existing between the blood and the walls of the blood-vessels. Or, in other words, there is in morbus maculosus a primary disease, either of the blood or of the walls of the blood-vessels, or of both together. In con- sequence of the negative results furnished by the examinations of the blood in genuine cases of the disease that have hitherto been undertaken, and of the absence of all macroscopic changes in the walls of the bloodvessels, and finally, of the obscurity and confusion of the etiological conditions under which the hemorrhagic diathesis not infrequently develops in concreto al- most instantaneously, to disappear again completely after a more or less prolonged existence — it is at present absolutely impos- sible to determine whether the mode of development in cases symptomatically identical is really always the same. Hence, simple as is the mere clinical fact of the existence in morbus maculosus of a transitory and essential hemorrhagic diathesis, and easy, as it consequently is, to define briefly and concisely the nature of the disease, it is in an equal degree difficult, and even for the present impossible, to answer the question as to its pathogenesis. On account particularly of this lack of a precise etiology and of a satisfactory histological and chemical founda- tion, we must always bear in mind the possibility that these cases, which resemble one another so closely in their clinical his- tories, may have had entirely different developmental histories. The genesis of the disease appears to us relatively most com- prehensible in those not infrequent cases where it occurs as an actual sequel to other severe and prostrating pathological pro- cesses, that is, when it is developed not during the existence nor immediately after the termination of the latter, but at a some- what more advanced period of the convalescence. It is certainly possible that the intercurrent appearance of the hemorrhagic NATURE AND PATHOGENESIS. 237 diathesis in such cases has some connection with the very pecu- liar and exceptional relations which frequently exist at that very time, between the volume of the blood on the one hand and the resisting power of the vascular apparatus on the other. For reasons which were given in detail, when speaking of anamic marasmus (comp. Vol. XVI.), it must be admitted, as proba- ble at least, that the general nutrition and functional power of all the tissues suffer, during the course of severe diseases, in direct proportion to the impairment in the composition of the blood, and that the walls of the blood-vessels, and particularly those of the capillaries, are involved in this nutritive and func- tional decadence. As a result, the capillary walls become more brittle and more permeable. This condition, in itself and at first, merely predisposes to hemorrhages ; but when it has reached higher grades of development, and especially when auxiliary exciting causes are present, it may lead to hemorrhages even dur- ing the course of the severe primary affection. Two questions now present themselves, viz. : why this hemorrhagic diathesis does not manifest itself more frequently as a symptomatic affection during the course of the primary diseases which beget it i and why, on the other hand, it should occur relatively as often during convalescence in a more independent manner and as a sequel ? In our opinion the correct answer to the former question is, that the great diminution in the force of the heart's action and the marked decrease in the volume of the blood, which occur so com- monly in the course of severe pathological processes, present an obstacle to the actual outbreak of the hemorrhagic diathesis which is sufficient to keep it perfectly latent in very many cases. In the same way in the normal course of convalescence, the recovery of the cardiac power and the increase in the volumes of the general nutritive fluids produced by the assimilation of new albuminous material, go hand in hand with the restitution of the functional and nutritive integrity of the capillary walls, so that at no phase of this process is there any marked disproportion between the increasing cardiac energy and the increasing mass of the blood on the one hand, and the increasing resistance of the capillary walls on the other. If, however, during the course of convales- cence from a severe disease, the restitution of the walls of the 268 IMMERMANN.—MORBUS MACULOSUS. vessels does not keep pace toith the regeneration of the blood- mass and the increase in the energy of the heart s action, it is evident that we must regard this want of harmony between the usually synchronous processes of recovery as a predisposing cause of the development of a transitory hemorrhagic diathesis. We believe in fact that the not infrequent appearance of morbus maculosus, during convalescence from typhoid fever and other severe diseases, is to be accounted for in this way. This opinion is supported by the fact that in such cases the outbreak of the hemorrhagic diathesis frequently appears immediately after some unusual movement, etc., which causes temporary excitement of the heart's action: as an instance Ave may mention the first attempt to stand up and walk about. This explanation, however, is applicable only to those cases in which the purpura hemorrhagica is developed during conva- lescence from some severe disease. Such cases, however, consti- tute only a small minority of the whole. We must here again call attention to the fact that the disease often attacks without any apparent cause individuals who were previously in perfect health. In such cases we cannot, of course, speak of a prece- dent diminution in the volume of the blood, nor of an alteration in the walls of the blood-vessels dependent upon anemia, nor of a want of harmony in the regenerative processes. Here the pathogenesis is evidently different, and we may add at once that it is as yet entirely inexplicable. The examination of the blood has shown that there is no gross, palpable anomaly of that fluid which can be regarded as the cause of the supposed alteration in the walls of the vessels. Hence, in the search after an a priori explanation, we are driven either to assume the existence of imperceptible changes in the blood, ex. gr., the importation of a deleterious, miasmatic principle, or to recognize as the basis of the hemorrhagic diathesis a peculiar disease of the blood-vessels more or less independent of the condition of the blood. Opposed to the theor}^ of the miasmatic origin of morbus maculosus is the fact that the disease is neither epidemic nor endemic, but that the overwhelming majority of the cases are perfectly iso- lated. A microscopically demonstrable primary disease of the walls of the blood-vessels, at least in the rapidly fatal cases, does COMPLICATIONS AND SEQUELAE. 269 not appear to exist (comp. Complications and Sequelae). It can- not therefore be assumed in explanation of the phenomena. The theory of a neurotic disease of the vessels has been suggested by some recent experiments performed by Nothnagell on animals, which prove that multiple hemorrhages occur in the lungs after slight lesions of certain points in the cortex of the brain. This theory is perhaps more tenable than the others. We will refrain, however, from further speculations regarding the pathogenesis of the apparently spontaneous cases of morbus maculosus. Since we cannot explain them satisfactorily, Ave prefer to Avait till further investigations and anatomical observations shall have thrown more light upon this very obscure subject. Complications anel Sequela. A particularly important and very frequent complication of morbus maculosus is the acute ancemia which is developed in severe cases as a result of the hemorrhages, and which, provided the disease does not end fatally, persists for a time after the hemorrhagic diathesis has disappeared. Of very slight prog- nostic importance, but still interesting, is the development of cutaneous A\meals or urticaria which has been observed by some authors. This complication appears to occur chiefly in those cases Avhich present severe gastric symptoms (Henoch2 and Scheby-Buch s). Starting from the fact that urticaria usually occurs in connection Avith disturbances of the digestive appara- tus, Scheby-Buch has suggested that in these cases it may be more directly dependent on the gastric disturbances than on the hemorrhagic diathesis. A fortunately very rare complication and sequel of severe cases of purpura is the mortification and ulceration of the mucous coat of the intestines, sometimes pro- duced by widespread and multiple hemorrhagic infiltrations. This has been observed and described by Reuniont, Herard, O. Weber, E. Wagner, and others. The intestinal ulcers produced in this manner shoAved no tendency to healing, and induced 1 Centralblatt fiir die med. Wissensch. 1874. Nr. 14. 21. c. p. 403. 3 1. c. p. 490 sqq. 270 IMMERMANN.—MORBUS MACULOSUS. profuse diarrhoea, which subsequently in all the cases proved fatal through exhaustion. Zimmerman ' reports a case of mor- bus maculosus Werlhofii of long standing, in which death was due to perforative peritonitis, the result of multiple eschars in the intestinal walls, which penetrated as far as the serous coat. The Avails of the smallest arteries in the neighborhood of the necrotic places in this case were found on microscopic examina- tion to be thickened in a peculiar manner. The increase in thickness affected particularly the adventitia, which was filled with countless rounded cells and nuclei. Zimmermann, after describing these appearances, refers to the peculiar cases of "Periarteritis nodosa'' reported by Kussmaul and Mayer,2 and calls attention to the resemblances as well as the great discrepan- cies existing between their cases and his. We readily admit that the differences in the clinical histories and the post-mortem ap- pearances are too great to warrant us in employing the peri- arteritis nodosa discovered by Kussmaul and Mayer as a basis on which to build up a theory of the hemorrhagic diathesis present in morbus maculosus Werlhofii. Diagnosis. Since the morbus maculosus Werlhofii, as a clinically dis- tinct disease, possesses a marked hemorrhagic character, it can be confounded only with such other processes and conditions as possess likewise a hemorrhagic habitus. For instance, it may be, and in fact often has been, confounded with scurvy; also, but less frequently, Avith the congenital and habitual pre- disposition to hemorrhages which characterizes haemophilia. The differential diagnosis from leukaemia and pseudo-leukaemia, and from progressive pernicious ancemia, may also present diffi- culties. Finally, Ave must also mention the possibility of con- founding it with the symptomatic hemorrhagic diathesis Avhich sometimes accompanies or complicates various severe morbid processes. 1 Archiv der Heilkunde. Bd. XV. (1874). S. 167. 2 Deutsches Archiv fiir klin. Med. Bd. I. (1866). S. 484. DIAGNOSIS. 271 The diagnostic points between morbus maculosus and scurvy are derived both from the etiology and the symptomatology of the two affections. This duplication of the differential points makes the recognition of typical cases of one or the other dis- ease perfectly easy and certain; it is, moreover, invaluable in the more doubtful cases, since either the etiological or the symp- tomatic differences are separately sufficient for the differential diagnosis. Scurvy is a hemorrhagic affection Avhich is almost without exception developed only under the influence of long and severe privation, and which, moreover, as a rule, prevails as an endemic or epidemic disease. Its development is almost never an "apparently spontaneous one," and isolated cases of the disease are relatively very rare. Morbus maculosus, on the other hand, as a rule, occurs sporadically, and in very many of the cases the disease is " apparently spontaneous." In those other cases where the anamnesis shows that the hygienic condi- tions Avith regard to habitation, food, etc., have not been good, the fact that the disease has attacked only one individual will weigh heavy in the balance against scurvy, provided it can be shown that man}' persons were exposed to the same unhealthf ul surroundings as the patient, without being similarly affected. These etiological differences are supplemented by not less important symptomatic differences, which prove of very great value in the diagnosis of doubtful cases. In the first place, the majority of cases of scurvy are preceded by a distinct and protracted stadium prodromorum. During this time usually no hemorrhages occur, but a marked general cachexia with peculiar characteristics is developed. The hemorrhagic dia- thesis of morbus maculosus, on the contrary, generally appears suddenly and without warning, or at most, after a very short prodromal indisposition. In none of the cases, at least in the beginning, is there anj^thing like the scorbutic cachexia with its signs of an intense primary depravation of the general nutri- tion, which is for the most part independent of any hemorrhagic attacks. It is true that great impairment of the general health and of the bodily powers may be developed in the course of severe cases of morbus maculosus, but it is then entirely of a secondary and ancemic character, and its degree is dependent 272 IMMERMANN.—MORBUS MACULOSUS. upon the frequency and copiousness of the hemorrhages. Finally, there are also some striking differences in the character of the hemorrhagic symptoms in the two diseases. In the first place, the hemorrhagic inflammation of the gums, which is so charac- teristic of scurvy, is wanting in morbus maculosus, although in the latter, simple non-inflammatory hemorrhages from the gums are not infrequent. Moreover, the local symptoms in general of scurvy possess not only a hemorrhagic, but also an inflammatory character, which in morbus maculosus is either entirely wanting, or present only to a very limited extent. Further, these inflammations in scurvy sIioav a great tendency to end in ulceration and mortification of the tissues affected. Even after all that has here been said, it might still with some appearance of reason be asserted, that between scurvy and morbus maculosus there exists only a quantitative distinction ; that the former is merely a more severe, and the latter a milder form of one and the same general disease, and that consequently it is superfluous to speak of a differential diagnosis between the two. Opposed to this view, however, is the interesting fact that certain severe hemorrhagic accidents, particularly the exhausting and often fatal bleeding from the nose, stomach, intestines, uri- naiy passages, and female genital apparatus, are much more frequent in morbus maculosus than in scurvy, Avhile, on the contrary, the equally dangerous hemorrhages into the pleura and pericardium are more frequent in the latter. Hence, it is not so easy, on account of this very difference in the topographi- cal distribution of the most frequent varieties of the hemorrhage, to discuss the differences in the intensity of the two processes. We must, on the contrary, admit, whether Ave Avish to or not, that they differ in quality with regard to the symptoms as well. Well-marked cases of morbus maculosus cannot easily be mistaken for hamophiliei, since Ave include in the former disease only those cases in \vhich the hemorrhagic diathesis does not depend on an inherited predisposition, and does not constitute an habitual pathological condition, but in which, on the con- trary, it is developed in an isolated manner, and is, as a rule, of a transitory nature. The following additional points of difference betAAreen the tAvo affections may also be mentioned: the somewhat DIAGNOSIS. 273 greater frequency of morbus maculosus in the female is con- trasted with the decided predilection of hemophilia for the male sex ; the usually trivial results of slight injuries in morbus maculosus as compared with the great danger attending even the very smallest wounds in hemophilia; finally, the absence in purpura hemorrhagica of all those symptoms of an habitual fluxionary diathesis and plethora, which seem to be rarely wanting in hemophilia and are particularly marked just before the occurrence of the spontaneous hemorrhages. In general, therefore, it is not difficult to determine whether a given case of the hemorrhagic diathesis belongs in the category of morbus maculosus or of hemophilia. It must not be forgotten, hoAvever, that there are also rudimentary forms of hemophilia which remain latent during the greater part of life, and only manifest themselves transitorily, perhaps only once, perhaps oftener. Such cases, on account of this anomalous behavior, simulate morbus maculosus pretty closely. The most important diag- nostic point in all such cases of hemophilia is furnished by the fact that the hemorrhagic diathesis in question, although it appears in concreto to be only a transitory affection, occurs within the consanguineous circle of a bleeder family, other members of which have suffered from the more developed forms of hemophilia. Where this criterion is wanting, Ave may con- fidently exclude hemophilia, and diagnosticate a simple tran- sitory hemorrhagic diathesis (morbus maculosus Werlhofii). On the other hand, morbus maculosus has been known in many cases to recur frequently throughout the entire life of an individ- ual (Rohlfs).1 Behavior like this indicates a special and prob- ably congenital tendency to hemorrhagic accidents, and is very suggestive of genuine hemophilia. But even under such circum- stances no man would henceforth be excusable in making a diagnosis of true bleeder disease, unless the proof of the heredi- tary nature of the disease, particularly its indirect transmission from the side of the mother, can be adduced. To make the diagnosis certain, the patient should be of the male sex, and finally, it must be shown that during his free intervals, any acci- 1 Memorabilien. Bd. XX. S. 433 (1875). VOL. XVII.—18 274 IMMERMANN.—MORBUS MACULOSUS. dental traumatic hemorrhages prove exceptionally intractable. If these signs are not present, and there is no question of the possible existence of other processes, the case in question must be considered one of morbus maculosus, and not of hemophilia. Morbus maculosus may be distinguished from the hemor- rhagic diathesis of leukcemia and pseudo-leukemia by an exami- nation of the spleen and lymphatic glands, and (in leukemia) also of the blood. More difficult, and in fact only possible with the help of the microscopic analysis of the blood during life and of the examination of the medulla of the bones after death, is the differential diagnosis between simple morbus macu- losus and myelogenic leukamia, in those cases of the latter affection in which the spleen and lymphatic glands do not par- ticipate to any marked extent in the hyperplasia of the medulla of the bones. As an example of this Ave may refer to a case from the clinic at Basel, the history of which was, for diagnostic reasons, briefly detailed in the chapter on Progressive Pernici- ous Anemia. This case was admitted with a diagnosis of mor- bus maculosus Werlhofii, and was at first regarded by us as progressive pernicious anemia, but it was afterwards shown to be neither the one nor the other, but a subacute myelogenic leukemia. This was positively proved, even during the lifetime of the patient, by the examination of the blood. Similar cases have probably often occurred, and been wrongly diagnosed as cases merely of severe morbus maculosus with fatal termination. The diagnostic separation of progressive pernicious ancemia from morbus maculosus, is in our opinion of special importance, because we are convinced that the casuistic literature of the latter disease includes many cases which should properly be classed as progressive pernicious anemia, and not as Werlhof s disease. An important and actually cardinal differential point in this case is that in progressive ancemia the hemorrhagic diathesis is always developed on the basis of a pre-existing, plainly evident, and very marked poverty of blood, and is con- sequently secondary; Avhile, on the contraiy, in morbus macu- losus the hemorrhagic diathesis is primary, and the anemia which subsequently appears in the severer forms of the disease is secondary to it. When in a given case, which presents a TERMINATIONS AND PROGNOSIS. 275 marked degree of oligemia in addition to petechie and other hemorrhagic symptoms, we have by exclusion narrowed the question of diagnosis down to progressive anemia and Werl- hof s disease, it is in our opinion only necessary, in order to decide the question, to ascertain the chronological order in which the principal symptoms presented themselves, or, in other words, to determine accurately from the anamnesis whether the hemorrhagic diathesis or the extreme anemia Avas the first to appear. The confounding of morbus maculosus with symptomatic predispositions to hemorrhage of other kinds than the above is neither theoretically excusable, nor indeed likely to occur often in practice; for the existence of some severe primary disease in connection with the latter can almost always be established without much difficulty by the demonstration of the local and general symptoms produced by it. When the examination of the patient has been conducted with proper care, and sufficient attention has been paid to the etiological conditions, it is almost invariably possible to decide, without hesitation, whether the hemorrhagic diathesis in question is only symptomatic, or con- stitutes an essential disease which can properly be called mor- bus maculos Duration, Terminations, and Prognosis. Even if we except the fatal cases, which sometimes run a very rapid course, the duration of morbus maculosus is, as a rule, short. In the majority of the cases it lasts only from two to four weeks. This includes also the duration of the consecu- tive anemia, when it is not very extreme. The duration of the hemorrhagic diathesis itself is often much shorter, say from five to fourteen days. In many cases, however, the disease is more protracted, in consequence of repeated relapses of the petechial eruptions and the internal hemorrhages, or on account of the intense grade and slow disappearance of the consecutive ane- mia. Many weeks and even months may then pass by before the patient is completely restored to health and the last traces of the disease have disappeared. In the majority of the cases 276 IMMERMANN.—MORBUS MACULOSUS. the disease terminates more or less rapidly in recovery. In some very rare cases it is followed by-sequela, and finally not a few of the cases end fatally. Death is due to acute anemia, and generally at the acme of the disease. The danger of its occurrence increases in direct proportion to the profusion and number of the hemorrhages, and to the individual intolerance of the patient to loss of blood. The prognosis depends upon the grade of the disease and the bodily constitution of the patient. It is in general rather favor- able than otherwise. It must not be forgotten, however, that cases which were at first very mild and apparently harmless, sometimes very rapidly change their character and become ma- lignant. This happens when the hemorrhages, which have pre- viously been slight, suddenly and usually Avithout any known cause become dangerously copious and at the same time begin to affect different parts of the body. The character of the dis- ease thus becomes suddenly severe and immediately threatening. It is therefore never possible in the commencement of a case of morbus maculosus to make a positive, favorable prognosis. On the other hand, a fatal result cannot be certainly predicted, even in those severe cases where the patients are exhausted by loss of blood, and lie in a condition of the deepest prostration. For experience has taught us that even a very intensely developed hemorrhagic diathesis in this disease may disappear quickly and completely, and that the patients under such circumstances, though perhaps with the greatest difficulty, finally recover from the condition of dangerous prostration into which they had fallen. It is evident, lastly, that the prognosis in the individual cases of morbus maculosus will depend greatly on the treatment em- ployed. By the employment of appropriate measures any imme- diate and threatening danger may often be greatly diminished, while a neglect of the proper precautions may directly hasten a fatal termination. Treatment. A rational prophylaxis against morbus maculosus Werlhofii is for the present impossible, because the causes of the disease TREATMENT. 277 are as yet absolutely unknown. For the same reason we cannot with any propriety speak of the fulfilment of the indicatio cau- salis, in the strict sense of the term. It is, nevertheless, advis- able in all cases of the disease to improve the hygienic surround- ings of the patients, wherever they are found to be deficient or bad. Among the lower classes, who are in general badly housed, badly clothed, and badly nourished, this is best accomplished by promptly placing the patients in well-regulated hospitals. AVhen, on the contrary—and this is just as often the case in this disease—the surroundings of the patients are all that can be desired, the efforts of the physician, aside from the maintenance of this favorable state of affairs, must necessarily be confined to fulfilling the indicatio morbi, to the symptomatic treatment of the case. The indicatio morbi calls for measures directed against the existing hemorrhagic disposition. Upon this point clearer and more reliable therapeutical rules could be laid down if more were known concerning the nature of those anatomical and func- tional anomalies in the vascular apparatus or the blood, which are the cause of the hemorrhages in each individual case. Since Ave are so much in the dark in these particulars, the measures Avhich are usually adopted in the essential treatment of the dis- ease must be regarded as empirical rather than rational in their nature. Above all, it appears to us dangerous to prescribe for all cases the same dietetic and medicinal regimen, based upon some positive, preconceived opinion. It is, in fact, dangerous to give others any positive directions about the treatment to be fol- lowed. This applies particularly to the practice of venesection and local blood-letting, which was formerly, and has been to some extent even recently recommended, especially by English and Italian physicians, on the ground that morbus maculosus depends upon a fluxionary diathesis. Clinical experience has convinced us that this, if true at all, can be so only exception- all}'-. In the great majority of cases, the entire behavior of the patients at the time of the outbreak of the diathesis speaks against such a supposition. The patients are liable to be called on during the course of the disease to stand the loss of a great deal of blood, and, moreover, are frequently of a habitus that 278 IMMERMANN.—MORBUS MACULOSUS. does not bear bloodletting; hence, it is certainly inadvisable to resort with undue zeal to venesection, leeches, etc., which would reduce them at once to an anemic condition. Less dangerous, but still of doubtful therapeutic value, is the internal adminis- tration of the mineral acids, and particularly of sulphuric acid, in the form of the elixir acidum Halleri, which, since it was first recommended by Werlhof, has enjoyed a certain, but probably wholly undeserved reputation in the treatment of morbus mac- ulosus. The mineral acids, with sulphuric acid at their head, are said to prove useful when administered internally, not only as hemostatics against actually existing hemorrhages, but also against the tendency to hemorrhage; or, in other words, against the presumptive disease of the blood and the blood-ves- sels. For ourselves, we must say that in the hemorrhagic diathe- sis in general, and in morbus maculosus in particular, we have never seen any noticeable results from the administration of sul- phuric or of any other of the mineral acids (nitric, phosphoric, muriatic) in their usual forms and doses. We cannot, conse- quently, join in the praises which others lavish on them. The vegetable acids (acidum aceticum, tartaricum, citricum) seem to be even less efficacious. They have been repeatedly tried in morbus maculosus, but with the same negative results as in scurvy. It is an interesting fact that the use of afresh vegetable diet, which is usually so beneficial in the treatment of scurvy, has been proved to be utterly ineffective against morbus macu- losus (Curran and others). This is another argument against the identity of the two diseases. Mignot, Argaing, and Loufflet state they have obtained good results from the internal administration of the solution of chloride of iron in doses of one to five drops every two hours, in a mucilaginous vehicle. Other authors recommend ergot, and others still acetate of lead in half-grain doses, several times a day. Our own personal observations, how- ever, have convinced us that none of the above-named reme- dies, except perhaps the last, exerts any influence worthy of mention on the hemorrhagic diathesis in cases of morbus macu- losus. Even the efficacy of lead seems to us as yet rather prob- lematical. Respecting the value of oil of turpentine, former!y recommended by Neligan, Sewruch, Curran, and others, Ave have TREATMENT. 279 no recent observations. Since, therefore, there is no special medication which can be recommended as reliable, the occur- rence of the hemorrhages must be guarded against as far as pos- sible by a strict enforcement of dietetic treatment. Here careful attention on the part of the physician is often very useful, for many hemorrhages are undoubtedly directly provoked by the non-observance on the part of the patient of a proper regimen. In the first place, every direct mechanical injury of the body must be guarded against, since a push, a blow, a jar, or strong pressure on any part, may cause a hemor- rhage. Secondly, and particularly in the early stages of the dis- ease, everything which is liable to excite the heart's action, and thus increase the internal pressure in the vessels, must be avoided. Mental and bodily rest must be strictly enjoined. The patients must not only remain in bed, but they must avoid all active movements in the bed. The sick-room should be kept cool, and the patient must not be too warmly covered. The food must be nutritious, but bland, must be taken cold, and should consist chiefly of milk. Of other drinks, except when counter- indicated for some reason, iced water and lemonade are the most suitable ; they may be given in small quantities as often as the thirst may demand. On the other hand, the ingestion of large quantities, even of the above-named kinds, must be prohibited decidedly, since the entrance of large quantities of fluid into the blood may induce a transitory condition of plethora ad, vasa, which may result in hemorrhage. Hot or even Avarm drinks must not be given ; the same may be said in general of alcoholic spirits, although certain symptomatic indications may at times demand them. It is very desirable that the bowels should be moved regularly, since the accumulation of feces in the intestinal canal is well known to lead to collateral fluxions in the upper part of the body — a condition favorable to the occurrence of hemorrhages. Existing constipation should be treated princi- pally by clysmata, or at all events, by very mild cathartics {e.g., oleum ricini). Drastics are positively interdicted, as they directly provoke intestinal hemorrhages, and, aside from that, often lead to a premature prostration of the strength. The indicatio symptomatica demands first of all a direct 280 IMMERMANN.—MORBUS MACULOSUS. treatment of the existing hemorrhages. For the measures to be adopted against the attacks of epistaxis, hematemesis, hematu- ria, etc., we refer the reader to the chapters on Hemophilia and Scurvy. We think it unnecessary in this place to add anything to the directions there laid down, except perhaps that they must be carried out with proper energy. The articular pains and the swelling of the joints in the so-called "purpura rheumatica " require narcotic liniments, or, if the pain be very severe, mor- phine internally or subcutaneously. A special treatment of these symptoms is, however, often unnecessary, as they disap- pear spontaneously after a short time. It is of great importance that, during the height of the disease in severe cases, due attention should be paid to the symptoms of the complicating acute ancemia, which is liable to be devel- oped sooner or later in consequence of loss of blood, and is often fraught with immediate danger to life. Moreover, after the cessa- tion of the hemorrhages and the final disappearance of the hemorrhagic diathesis, ancemia, which usually remains behind, requires appropriate treatment. In regard to the first point, Ave refer the reader to the directions given elsewhere, and particu- larly to those given in connection with the treatment of hemo- philia. We will only add here that the indications for the use of stimulants, such as wine, champagne, cognac, and camphor, are often enough present during the course of morbus maculo- sus, viz., whenever the weakness is increasing, and the action of the heart threatens to cease. It is well, however, to confine the extensive use of these excitants to the occasions of actual neces- sity. The operation of transfusion does not promise much in morbus maculosus, since it cannot lessen the danger of new hemorrhages. The results of the operation, whenever it has been practised in cases of Werlhof s disease (Juergensen, Th. Smith, and others) were invariably unfavorable. The eifter-treat- ment of morbus maculosus, or the removal of the residual ana- mia, requires the use of nutritious etnd easily digested food, fresh air, and other dietetic roborantia, and especially the admin- istration of preparations of quinine and of iron, in increasing doses. It must be laid down as an absolute rule, however, that the administration of the preparations of iron should not be be- TREATMENT. 281 gun till after the hemorrhagic diathesis has completely disap- peared, and not until the patient has for several days been en- tirely free from even the slightest signs of its existence, such for instance as a fresh outbreak of petechie on the legs after the convalescent has been walking about for some time. The too early use of iron has in many cases evidently led to relapses of the disease. Hence, although we believe that a bold adminis- tration of iron is of the very greatest value during convales- cence, we are also convinced that experience has proved it to be unadvisable, and even absolutely counterindicated, during the actual persistence of the disease. I'll POISONS, y BOEHM. FIRST PART. Poisoning by Metalloids; Acids ; Alkalies, Earths, and their Salts. FIRST DIVISION. Poisoning by Metalloids. CHAPTER I. POISONING BY CHLORINE. Notwithstanding its manifold applications in the arts as a bleaching and disinfecting agent, chlorine does not belong among the especially important substances of practical toxicology. In most instances we have to deal with cases of poisoning by the action of free gaseous chlorine on the organs of respiration, and more rarely with cases of internal poisoning by the aqueous solution, as chlorine water or solutions of bleaching salts (alka- line hypochlorites, javelle water, Labarraque's solution), which, as well as the so-called chlorinated lime, readily afford appreci- able quantities of chlorine gas. Still, in poisoning by the last- named substances, the caustic action of the alkali must also be taken into consideration.1 Chlorine gas is distinguished by a characteristic unpleasant smell, and by its property of strongly irritating the mucous membranes; it is of a greenish color and readily soluble in water. The peculiar chlorine odor also pertains to chlorinated lime and the hypochlorites. The hostile relation which chlorine bears to the animal organ- ism apparently arises from the strong affinity of this element for 1 Cf. Chapter on poisoning by lyes. 286 BOEIIM.—POISONS. hydrogen, with which it forms hydrochloric acid. According to the researches of Bryk' in regard to the action of chlorine on animal tissues, the ammonia formed by the decomposition of the protein substances unites with the chlorine to form ammoni- um chloride. Dilutions of blood and albumen are coagulated by chlorine, the former being changed into a dark brown greasy mass,—hydro- chloric acid, according to Eulenberg,2 being formed at the same time. The question whether the action of chlorine is to be regarded essentially only as a local irritant and caustic, a view which has been entertained by Hermann,3 or Avhether, besides the local irri- tation, a more constitutional action must be assumed, cannot yet be settled with certainty. The possibility of the existence of free chlorine in the blood has been very properly rejected by Hermann, and we can now only question whether the hydrochloric acid or other combina- tions, as yet unknown, which the chlorine forms in the blood or before entering into it, exercise a constitutional action. The paralysis of the heart, observed in animals in consequence of the action of chlorine, is brought up by F. Falk * as a positive indi- cation that the chlorine is changed to hydrochloric acid, since it is well knoAvn that the acids paralyze the hearts of frogs. The disturbances of nutrition, observed among workmen who have been exposed for some time to the influence of chlorine fumes, might also perhaps be considered by some as confirming the above idea of a constitutional effect produced by chlorine. In all this, however, we are still confined to the domain of pure hypothesis so long as the change from chlorine to hydrochloric acid in the blood during circulation, or the absorption of .hydro- chloric acid, Avhich has been formed from chlorine in the stomach and intestinal canal, has not yet been shown. Accurate exami- nations of the urine Avould soon settle this point, since evidently such an appreciable addition of hydrochloric acid would dimin- 1 Virchow's Archiv. 2 Die schadlichen und giftigen Gase. S. 216. 3 Experimentelle Toxicologic. S. 143. 4 Vierteljahrschr. f. gerichtl. Med. v. Eulenberg. 1872. N. F. XVI. METALLOIDS.—CHLORINE. 287 ish the alkalies, and would, moreover, cause an increased elimi- nation of chlorides. Eulenberg thinks that the blood-corpuscles, under the action of chlorine, lose their capacity for respiratory changes by the decomposition of the coloring matter which they contain. This might happen if the two should come directly into contact with each other. Falk, who was able to produce the same effects upon frogs which had been bled (through the action of salt) as upon those in a normal state, by means of chlorine, concludes from this that it is superfluous to suppose an alteration in the blood-corpuscles as the effect of the action of chlorine, and regards the result of his experiment as an indication that chlo- rine in itself acts as a poison upon the heart. But we cannot see why the chlorine may not be changed into hydrochloric acid in its action on these frogs which have been bled. The fact that a decided odor of chlorine has been noticed in the brain and organs of respiration by Cameron,' on post-mortem examination of a person who had died from poisoning by chlo- rine, does not seem to us a sufficient ground for assuming that free chlorine circulated in the fluids and blood during life. The primary effects of the poison when inhaled are, firstly, irritation of the nerves in the mucous membrane of the organs of respiration, and, secondly, certain reflex actions caused by that irritation. To the latter belongs the spasmodic closing of the glottis which in former times was generally regarded as the cause of death in chlorine poisoning. Von Hasselt and Mulder,5 however, observed that rabbits placed by them in an atmosphere of chlorine gas did not perish from spasm of the glottis, but breathed the gas for some time. Recently F. Falk confirmed this observation, and further noted that the closing of the glot- tis on inhalation of chlorine lasted but a very short time, and the animal before succumbing dreAv several deep breaths with the glottis open. He further found that the spasm of the glottis is a reflex action brought into play by sensible irritation of the nerves of the larynx itself, or of that portion of the air-passages which is situated above it, for it does not take place if the 1 Dubl. Quart. Journ. 1870. Cf. Hirt, Krankheiten der Arbeiter. I. 8 von Hasselt-Henkel's Toxicology. II. 288 BOEHM.—POISONS. animal is made to inhale the gas through a tracheal fistula below the larynx. The disorders resulting from the introduction of solutions containing chlorine into the digestive tract are of a gastrointes- tinal nature. Besides chemists and apothecaries, who occasionally, through lack of skill or by mischance, poison themselves with chlorine fumes, workmen in certain chemical works (as chlorinated lime works and bleacheries) are especially exposed to the prolonged influence of larger or smaller amounts of the gas. But all authors agree in this, that the evil effect on the health thereby caused, aside from some chronic affections to be described farther on, is not very decided, and that the workmen may live to an advanced age. It is only in rare instances that chlorine-poisoning has taken place in any other way than those already mentioned, and these cases were almost all brought about through accident. In the literature of the subject we have found a single instance com- municated by Barbet,1 in which a man committed suicide by taking javelle water (sodic hypochlorite).1 Injudicious disinfection of sick-rooms by chlorinated lime may under some circumstances also cause poisoning. Halforts has reported cases of illness caused in this way, and also remarks that during a cholera epidemic some of the post-office officials, whose duty it was to disinfect the letters, contracted phthisis in the performance of this duty. Up to the present time eleven cases of acute poisoning by chlorine have been recorded in the literature, five of which were observed by von Hasselt, two by Dieudonne, and one each by Mulder, Henkel,4 Simonson,6 and Cameron (1. c.); the case recorded by Simonson Avas the only one ending in recovery, the others being fatal. Under the head of Poisoning by Lyes, we have considered the 1 Journ. de med. de Bordeaux. 1843. ' Javelle water is potassic hypochlorite. The sodic salt is known as Labarraque's solution. —Translator. 3 Krankheiten der Arbeiter und Gewerbtreibenden. Berlin, 1845. 4 von Hasselt-Henkel. Toxicologic II. s Casper, Wochenschr. 1837. METALLOIDS.—CHLORINE. 2S3 cases which Tardieu' has reported of poisoning caused by bleach- ing fluids. As regards the amount of chlorine necessary to cause poison- ing, the fatal dose, etc., as may be readily understood, no specific data can be given. The more concentrated the atmosphere of chlorine, the more powerful the action. The fact, however, should be noted that the organism appears to accustom itself to the effects of moderate amounts of chlorine. Workmen in the above-mentioned establishments can live without discomfort in an atmosphere which causes severe irritation in those unaccus- tomed to it. The symptoms of acute chlorine-poisoning in human subjects consist at first in severe reflex phenomena: violent coughing, sneezing, flow of tears, sharp pains in the thorax, and dyspnoea. Moreover, after leaving the poisonous atmosphere these phenom- ena persist for some hours with varying intensity. If the poison acts for a longer time, more serious affections of the organs of respiration ensue, consisting in spitting of blood, difficult respiration, temporary spasms of the glottis, and a pneumonia which usually ends speedily in death. Vomiting- has been noted in several cases. What particular phenomena precede death in very acute poi- soning have not been clinically established. The statement, that workmen exposed for some time to chlorine fumes are predisposed to phthisis, has been absolutely denied by all recent authors. But almost all the persons affected lose flesh perceptibly, though they are not incapacitated for work thereby ; the face shows an unhealthy color, and they suffer from mild catarrh of the stomach and chronic bronchitis. In almost all cases the acuteness of the sense of smell is also diminished (Hirt). Moreover, the frequently proclaimed immu- nity of the workmen in question from cholera and other epidemic diseases,' is, according to Hirt, not an invariable rule. Regarding the lesions found after death in cases of chlorine- poisoning, we possess but little information. Cameron observed 1 fitude medico-legal sur l'empoisonnement. 2. Edit. Paris, 1875. 2 Christison, Treat;se on Poisons. VOL. XVII.—10 290 BOEHM. —POISONS. congested lungs, the bronchi filled with a bloody fluid, and inflammation of the trachea. As antidotes to chlorine-poisoning most hand-books recom- mend inhalations of hydrosulphuric acid or ammonia. In the first case hydrochloric acid and water [? Trans.] are formed, in the latter ammonium chloride. These agents under the most favorable circumstances can evidently only render the chlorine still in the air-passages harm- less, while they would only increase the irritation at the time of inspiration, but never remove it. But since the first result may be attained by simple removal from the agent which causes the difficulty, Ave would not recommend these antidotes to any one. Breathing hot vapor of water is apparently much better. For the distressing spasmodic coughing, Hirt recommends inhala- tions of chloroform. The deleterious effects of chlorine fumes, as Bolley * recently stated, may be quickly removed by inhaling small amounts of aniline. But whether this agent is suitable for the treatment of more serious cases of chlorine-poisoning, has not yet been determined. However, in most cases the most important thing is a judi- cious treatment of the symptoms, and we scarcely need make any further statement than that detailed rules cannot be laid down. CHAPTER II. POISONING BY IODINE (TINCTURE OF IODINE AND POTASSIUM IODIDE.) IODISM. Iodine and potassium iodide, as well as the corresponding bromine preparations, first assumed importance in practical toxicology Avhen they were introduced into the pharmacopoeia, and in their action on the animal organism the iodine prepara- tions present numerous analogies with those of bromine. But, while during the last few years numerous treatises have ap- peared on the action of bromine, researches on the pharmaceu- 1 Zeitschr. f. Hygiene. I. 1. METALLOIDS.— IODINE. 291 tical and toxicological action of iodine, aside from its relations to absorption and elimination, are surprisingly few in number. Iodine, though volatile like bromine and chlorine, is far less active when in the gaseous state than they. Since its boiling- point is very high (180° C), its violet vapors are liberated very sparingly at ordinary temperatures, and consequently exert a far less intense irritation upon animal organisms. The ordinary forms in which this substance acts poisonously are the alcoholic solution of iodine (tincture of iodine) and potassium iodide. Although these two preparations are chemically very different from one another, inasmuch as the one affords an element endowed with strong affinities, while the other is an entirely indifferent salt, yet they so far agree in their action, that the potassium iodide in the organism undoubtedly may have the specific effect of iodine. Their action on animal organisms only differs to this extent, in that the potassium iodide has not the active local action which gives the iodine tincture a place in the category of corrosive poisons. The alcoholic solution of iodine, as well as the aqueous solution of potassium iodide, is readily taken up by the fluids of the body, when applied to a mucous surface, to the subcutaneous cellular tissue, or to a serous surface. Tincture of iodine and potassium iodide (the latter in the form of iodine ointment) readily pass into the blood from the external skin, while aque- ous solutions of potassium iodide, like solutions of salts in gene- ral, under ordinary conditions are not absorbed. Roussin,1 who has made a careful study of this point, found that absorption took place through the cutis, when he allowed the solution to dry on the skin, when the body was sprinkled with pulverized potassium iodide, or when a shirt impregnated with the powder was worn. From this it appears as if the secretions of the skin, under these circumstances, favored the process of absorption, while in the presence of water their semi-fatty nature interposed an obstacle to the penetra- tion of solutions of salts into the sebaceous and sudoriferous glands. Numerous observations have been made on the mode and the form * in which the iodine preparations are eliminated. Accord- 1 Rec. de memoires de med., etc. milit. 3. Ser. XVIII. p 184. 2 Claude Bernard, Arch, gener. 1853. I. ; Lelimann, Physiol. Chemie; Strauch, Inaug.-Diss. Dorpat, 1852; Heubel, Inaug.-Diss. Dorpat, 1865; Lehwald, Abhandlun- 292 BOEHM. —POISONS. ing to these, they first appear in die saliva, combined with an alkali (as a rule, sodium), in from one and a half to ten minutes after they have been taken ; then, after some hours, in the urine, in the gastric juice, in the bile, and in the milk. Much the largest proportion of the iodine leaves the organism within twen- ty-four hours by way of the urine; a small amount, however, remains in the body for some time (even for several weeks), and appears, according to the researches of CI. Bernard and Heubel, to go through a sort of cycle, inasmuch as the salt eliminated in the saliva and stomach is reabsorbed in the intestinal canal, and the substance is only gradually eliminated in small quantities at a time by the kidneys. Iodine was also detected for several days in the milk of women who were suckling infants several days after it had disappeared from the urine.1 In a case reported by Rose,1 in which large quantities of tincture of iodine were injected into a large ovarian cyst after emptying it, the major part of the iodine was eliminated by the mucous membrane of the stomach, which Rose consequently considers as the especial organ for the elimination of iodine. In this case, which unfortunately stands alone, the woman was in other respects healthy. It is, moreover, especially striking that free iodine should make its appearance on the mucous membrane of the stomach, as was shown by Rose in the following manner: the stomach, on being laid bare at the autopsy, presented a brown color, which soon disappeared after it had been exposed to the air. The question as to how iodine and potassium iodide act in the organism has been much discussed. The fact that free iodine is never found in the urine or any other secretion (with the exception of the single case quoted above from Rose), but always some salt of hydriodic acid, leads to the inference that the free iodine in the tincture always exerts its affinity for hydrogen in the organism, and must combine with an alkali. Whether it enters first by substitution into the tissues, perhaps by circulating in the blood as iodine albuminate, and is then converted into an alkaline salt, or Avhether it simultaneously gen der schles. Gesellsch. f. vaterliind. Cultur. Abtheil. f. Naturw. und Medicin. 1861. III.; Roussin, 1. c. ; Melsens (cit. Husemann), Mor. Rosenthal (Wien. med. Halle, 1862), and others. 1 Virchow's Archiv. XXXV. 1866. METALLOIDS.—IODINE. 293 forms both compounds when brought into contact Avith the mu- cous coats, are still open questions. In any case the affinity of iodine for hydrogen sufficiently accounts for its corrosive action, which differs in no respect from that of other corrosive substances. The possibility of the exist- ence of free iodine in the blood of living animals for any length of time, is generally discredited. But if the specific action of tincture of iodine is explained on the hypothesis that the iodine albuminate is the vehicle of action, so much greater becomes the difficulty of explaining the analo- gous action of potassium iodide. An entire decomposition of this salt in the stomach is not readily conceivable. When it comes in contact with the common salt there present, the two must unquestionably be changed into potassium chloride and sodium iodide, but in this latter form it would become diffused in the blood, and would finally leave the body by way of the kidneys. But since we cannot expect any action of iodine from the indif- ferent sodium iodide, there remain to us but two ways out of the difficulty, viz., either to deny that potassium iodide possesses any specific action of iodine—as in fact many authors have done —or to assume that the conditions are such in the body that iodine is liberated from its alkaline salts. Several observations tend to favor this last view. While, on the one hand, Sartisson,1 avIio worked under Buch- 1161111's direction, has already in 1866 indicated the possibility that iodine may be set free from alkaline iodides by contact Avith certain animal secretions (saliva, nasal mucus), owing to the presence of nitrous and carbonic acids in them, quite recent- ly Kaemmerer' and Binz3 have brought forward new points of view, which tend to substantiate the assumption of a decompo- sition of potassium iodide in the body. Kaemmerer thinks that abundant opportunities are offered for it in the blood. In the first place, he supposes that through the agency of the carbonic acid, which is present in the blood in large quantities, hydriodic 1 Inaug.-Diss. Dorpat, 1866. a Virch. Arch. Bd. LIX. 1874. 3 Ibid. Bd. LXII. 1874. 294 BOEHM. —POISONS. acid is set free1 from the potassium iodide, with simultaneous formation of sodic bicarbonate. This acid, however, is at once decomposed by the oxygen of the blood, and iodine is set free. Binz has established experimentally the fact that iodine may be separated from potassium iodide in aqueous solutions in the presence of carbonic acid and protoplasm. Since these very conditions are everywhere afforded in the tissues of animal organisms, Binz concludes that in those tissues an analogous decomposition of potassium iodide takes place. He therefore locates the place of this change not in the blood, as Kaemmerer does, but in the tissues (lymph-glands, muscles), and makes the point against the last-named author, that the oxygen of the blood, which is stored up in the blood-corpuscles during life, and is intended for other functions, does not possess the requisite power of oxidation to effect the dissociation of the potassium iodide. All other processes of combustion during life most probably do not take place in the blood while circulating, but in the tissues. In the observations and discussions quoted there is an unmis- takable advance, and though the question regarding the locality Avhere the decomposition of the potassium iodide takes place, and regarding the exact mode of this decomposition in the organ- ism, cannot as yet be definitely settled, yet the fact itself can no longer be doubted, for nobody surely will again with Boinet2 attribute the action of potassium iodide to the potassium. Of the general action of iodine we are but imperfectly in- formed. The ingenious explanations to Avhich Kaemmerer resorts in his hypothesis regarding the separation of iodine in the blood are not founded on facts, and they take us no farther than do the theories which were current before his time, and which attribute to the iodine an influence in retarding and modifying the changes in the tissues. Yon Boeck,s with whose treatise Kaemmerer does not appear to be acquainted, has deter- mined by accurate quantitative estimation of the tissue-changes 1 That this is possible in very dilute aqueous solutions, has been shown by Struve. 2 Gaz. hebdom. 1864. 14. 3 Zeitschr. f. Biologie. V. 1869. METALLOIDS.—IODINE. 20,1 in the human subject, that the elimination of urea, durino* a course of treatment Avith iodine, suffers no change, and, there- fore, that we have no right to say that iodine has any effect on the tissue-changes in the animal economy. If Kaemmerer s explanation were true, that by the separation of iodine in the blood and by the formation of the correspondingly powerful oxidizing agent, potassium peroxide, an "increased activity in the tissue-changes and a more complete consumption of the con- stituents of the blood" must take place, we Avould infallibly be able to detect the result of this increased action in the substances eliminated by the excretions. But this, as has been stated, is not in the least degree the case. Moreover, the argument used by Kaemmerer in support of his theory, viz., that persons who are under treatment by iodine frequently lose flesh and become anaemic, can and must, as Ave shall see below, receive medically quite a different interpretation. At the same time the results obtained by Yon Boeck's obser- vations are also in direct conflict with the statements of Rabu- teau1 and Milanesi,3 both of whom, depending on researches made on human subjects, found, not an increase—as one should expect from Kaemmerer's theory, but a very perceptible diminu- tion in the amount of urea eliminated.3 Since, up to the present time, Yon Boeck, Avhose researches were made in Yoit's insti- tute, is the only experimenter who has taken every possible precaution to avoid those numerous sources of error which are inseparable from determinations of this kind (we refer especially to the control of the diet) ; and since, furthermore, the state- ments of the other two authors show a suspicious discrepancy in one particular, viz., that, notwithstanding the enormous dimi- nution in the amount of urea excreted, they were unable to establish any increase in the weight of the body—we must, for the present at least, attach greater value to the results obtained by the first-mentioned author. The disorders of nutrition which sometimes occur in cases of 1 Gaz. mod. de Paris. 1869. 3 Husemann, in Virch. u. Hirsch's Jahresber. 1873. 3 According to Rabuteau, this diminution was 40 per cent. (!) ; according to Mila- nesi, only from 4 to 19 per cent. 296 BOEHM.—POISONS. prolonged treatment with iodine, viz., the general loss of flesh and the complex of symptoms included under the designation of iodine cachexia, are not quite incomprehensible, even if Ave can- not prove experimentally some alteration in the tissue-changes. It is well known that in such cases of protracted treatment with drugs, as a rule, after some time the organs of digestion suffer more or less. Rose found in a case of iodine-poisoning, not only during life frequently repeated vomiting, but also after death, at the autopsy, extensive degeneration of the peptic glands, through which apparently a portion of the iodine had been eliminated from the organism. Although these important results were obtained in a case of acute poisoning, and are there- fore not to be forthwith utilized in explaining the more chronic disorders of nutrition which characterize iodism, yet facts are not wanting to show that also in protracted iodine-poisoning similar disorders in the functions of the stomach occur. In the by no means rare cases where, in spite of the accomplishment of the desired therapeutical effects of iodine, disorders of digestion are lacking, we usually find no loss of flesh or other cachectic phe- nomena. But where disorders of digestion are present at the time when the iodine treatment is begun, or develop in the course of it, they must, should the treatment last for any time, of neces- sity affect the general nutrition of the body, and so lead to loss of flesh. But then, without going out of our way to seek for an explanation in some mere hypothesis, we would naturally attri- bute this loss of flesh to the diminished amount of food taken and assimilated. The assumption of the existence of an "iodine fever" has also strengthened very much the obscure ideas that are held by some in regard to the influence of iodine on the tissue-changes, and in regard to a febrile consumption of the vital forces by that element. But it is impossible to find in the literature of this subject reliable data for the belief in the existence of such a spe- cific fever, unless we regard the general statements, respecting a feverish state and the like, as indicating the existence of such a fever. In cases in which the most marked symptoms of iodism were present, and in which all the indications of fever (such as flushed face, quickened pulse, etc.) were observed, Rose failed METALLOIDS.—IODINE. 297 to find the only true criterion of fever, viz., the rise in the tem- perature of the body. From this we are tempted to draw the inference that earlier authors were misled by the above-men- tioned symptoms into believing that there was such a thing as an iodine fever. From the general phenomena of iodine-poisoning, therefore, no information is to be gathered regarding the nature of this state. For further information regarding the other phenomena of iodism in man, the reader is referred to the Symptomatology. Meanwhile, we must here briefly consider the remaining experi- XflShtaHabors in regard to the action of iodine. Experimenters have not been lacking who have conducted long series of researches on themselves, on other men, and on animals, with the different preparations of iodine. Joerg1 and his pupils, Orfila2 and Magendie, devoted themselves specially to researches of this kind, but they established very little of importance besides the local and corrosive action of the poison. Magendie injected a drachm of the tincture of iodine into a vein of a dog, without thereby producing any effect. A feAv years ago M. Benedikt' also made a series of experiments on frogs, by which, however, our knowledge of the remote action of iodine was not essentially advanced. Iodine, like many other poisons, paralyzes the power of voluntary motion in frogs, and produces this effect apparently by affecting the spinal cord. Finally, Sartisson (loc. cit.) furnished evidence that the absorp- tion of iodine by the salivary glands is determined by nerve- influence, and not by the chemical affinity of the poison for the substances of which the gland is composed. For convenience of reference we may distinguish three cate- gories of etiological importance in iodine-poisoning: 1. The occupation (as an ordinary workman) of preparing iodine in chemical works ; 2. Accidental or intended poisoning with large amounts of tincture of iodine or Lugol's solution ; and 3. The therapeutic use of iodine, which alone leads to iodism in the restricted sense of the term. 1 Materialien zu einer kiinftigen Heilmittellehr. I. Leipzig, 1825. s Toxicolog. gen. I. 70. 3 Wien. med. Zeitschr. 1862. 298 BOEHM.—POISONS. The pernicious effects of iodine on workmen in iodine manu- factories are limited, according to a communication of Cheval- lier's,1 to the moment Avhen the iodine obtained by sublimation must be removed from the receiver. In this operation, which involves an exposure not merely to the fumes of iodine, but also to those of chlorine, the workmen, as a rule, experience a copious floAV of tears, and sometimes even slight fits of coughing ; serious inconvenience and illness never occur. Severe cases of acute poisoning arise either by the introduc- tion of iodine preparations into the stomach, or, as has recently often happened, by the injection of large quantities of tincture of' iodine orLugol's solution into serous cavities or sacs—especially into ovarian tumors. The number of cases on record arising from the first-mentioned mode is not large. We have already referred to the two cases reported by von Hasselt and Husemann, where suicide Avas committed by talking tincture of iodine internally; to these a third must be added, where (quite recently) two ounces of the tincture was taken internally.2 If Ave add to these the earlier cases mentioned by Taylor (poisoning of a woman by one ounce of the tincture), Gairdner (fatal poisoning of a child by one scruple of the tincture), and Gillespie (quoted by Husemann), the number of all the recorded fatal cases of poisoning by the internal administration of iodine amounts to six. The number of fatal cases from the injection of solutions of iodine into ovarian cysts is much larger. Yelpeau records twenty, Legrand three, which came under their personal observation. Here belong also the communications of Rose, who reports one fatal case, and one folloAved by recovery, in his own practice, and also mentions two other fatal cases of which he accidentally heard. The entire number of those fatally poisoned is, therefore, twenty-seven—a frightfully high figure, if we consider that they are exclusively cases Avhich have occurred as the results of medi- cal treatment. Finally, in this category belongs also the case recorded by M. Benedikt, where fatal poisoning followed the injection of tincture of iodine into the sac of a spina bifida. 1 Annales d'hygidne pub. 1842. s Reported by Hermann, of St. Petersburg, hi the Petersburg med. Zeitschr. XV. METALLOIDS. —IODINE. 299 The more chronic form of what might be termed therapeutic iodism occurs chiefly after the prolonged administration of small doses of iodine or of potassium iodide ; old strumous cases, and individuals who are very much run down through syphilitic cachexia, are especially predisposed to it. Aroneet1 has collected data from the literature on the frequency of the occurrence of iodism after the use of different preparations of iodine. In the case of tincture of iodine, he found only 20 cases AA-here the use Avas folloAved by serious effects; in 213 cases no mention was made of any injurious effects; Avhile in 303 it was expressly stated that the drug produced no detrimental effects. The use of Lugol' s solution of iodine Avith potassium iodide caused indi- cations of poisoning six times, and no hurtful action in 24.1 cases ; while from the use of potassium iodide alone Aroneet found that iodism had been produced in 40 cases. Although these different observations evidently Avarrant no safe conclusions, they perhaps convey a fairly correct impression of the frequency of iodism. ]S"o statistical communications on this point have been very recently made, but from the increased number of cases of iodine exanthemata observed, it may be surmised that, owing to the exclusive use of potassium iodide—for instance, in syphi- lis—iodism has rather increased than decreased. It is not possible to give exact data regarding the doses of iodine which may be considered as fatally poisonous. Our knowledge on this point is comprised in the communications which Ave have made above. Even small amounts, if admin- istered throughout a considerable period of time, suffice to produce iodism. In the fatal case reported by Rose, he injected into the ovarian cyst a drachm of potassium iodide, and five ounces of tincture of iodine—the amount ordinarily used in the operation—and then, after the lapse of a few minutes, removed from the cyst what remained of the fluid injected. If in washing out the cyst, however, in cases of this kind, Ave should neglect to do it thoroughly, very appreciable amounts of iodine may remain behind and become absorbed. Poisoning by large quantities of tincture of iodine taken 1 Inaug.-Dissert. Dorpat. 300 BOEHM.—POISONS. internally affords especially the phenomena of a severe affec- tion of the stomach and bowels. Yiolent burning pains are felt in the fauces, pharynx, and along the oesophagus, as well as in the stomach and abdomen. Generally vomiting follows, though sometimes only retching and nausea. The matter vomited is more or less blue (iodine reaction), if starchy substances were present in the stomach, and possesses the characteristic odor of iodine. The stools, which are usually profuse, are also colored with iodine ; at first they are of a pappy consistence, and later on bloody and slimy. At the same time there is almost always complete anuria. The general symptoms here described are identical with those observed in cases of poisoning by injection of solutions of iodine into ovarian cysts. To avoid repetition, we will here omit them. Death from internal poisoning by tincture of iodine may ensue within thirty-six hours, though of course much depends upon the amount of iodine contained in the dose. Poisoning after the injection of large quantities of iodine into ovarian cysts affords us an opportunity of observing the consti- tutional symptoms which are produced by large doses of this substance, without the disturbing influence of local symptoms ; for experience shows that the phenomena of peritonitis occur but seldom under these circumstances. The injection itself is sometimes accompanied or immediately followed by violent pains, which in sensitive persons may con- stitute so prominent a symptom as to overshadow all others, and under some circumstances may cause swooning. Next, in the course of a few hours after the operation, a state of excessive weakness and apathy, with increasing paleness of the face, cyanosis of the visible mucous membranes, and coldness in the extremities, is developed. The pulse, which grows steadily weaker and soon disappears entirely at the wrist, becomes ex- ceedingly rapid (170 beats per minute, and more); when the effects of the poison are at their height, it is only perceptible in the arteries near the heart, although the heart-sounds are forci- ble, and even increased in intensity. Within the first twenty- four hours these symptoms reach their maximum. Severe nervous symptoms are observed neither in the cases of poisoning by the stomach, nor in those of poisoning by injection; but there METALLOIDS.—IODINE. 301 is frequently repeated and painless vomiting of a copious waiery fluid, which appears on the scene pretty early. This vomiting is provoked by every attempt to take nourishment, but the very intense thirst can be more easily assuaged without such con- sequences. The stools are sometimes diarrhoeic. The secretion of urine is usually also entirely suppressed. * If the patient survive this stage, the paleness of the skin gives place on the second or third day to a deep flush, which is quite as striking in appearance. The temperature rises to the normal level, without overstepping it, and the pulse gradually diminishes in rapidity, and becomes again perceptible at the extremities. The vomiting persists, but the kidneys now begin to excrete a slightly albuminous urine. In the course of the next few days the characteristic exanthem, the angina, and the coryza show themselves. In the single case published by Rose, which, together with the case reported by Hermann, constitutes the sole basis for the present description, death ensued suddenly and without the least warning, on the tenth day—probably from paralysis of the heart. It is evident that the very limited casuistical basis for this clinical description can permit only a very cautious generaliza- tion. Still, Rose's observation is the more worthy of attention, since in its essential symptoms it presents a striking coincidence with the case of internal poisoning described by Hermann. In the latter, too, the characteristic disturbances of the circulation were very marked, and although the vomiting must perhaps be ascribed more to the local irritation of the stomach caused by the tincture, the complete absence of nervous symptoms Avas as noticeable as in Rose's case. The suppression of the urine Avas also the same in both cases. Rose, on the ground of his oavh observations, assumes the pathognomonic effect of poisoning by iodine to be a prolonged arterial spasm which produces the suppression of urine as well as the symptoms of paleness, weakness of the pulse, and cold- ness. Naturally such a universal contraction of the arterial sys- tem presents an obstacle to the circulation of the blood which forces the heart to excessive exertion—hence the exceedingly quick pulse (by irritation of the accelerating fibres 1). In Rose's 302 BOEHM. —POISONS. oavii case it finally led to paralysis of that organ. The cessation of this spasm is followed by excessive reddening of the skin and the relative rise in temperature, phenomena which probably led to the erroneous assumption of an iodine fever. The vomiting, which persists throughout the entire course of the symptoms, and is accompanied by pretty intense sensitive- ness to pressure over the region of the stomach, is ascribed by Rose to the material alterations in the mucous membrane of the stomach, which are excited, as has been already stated, by the elimination of the iodine through the peptic glands. Before entering upon the description of those cases of poison- ing which are due to the internal use of the preparations of iodine in small quantities, we must mention the fact, that some- times individuals, after taking a single moderate dose, suffer from symptoms of poisoning (vomiting, diarrhoea, etc.), Avhich are quite out of proportion to the amount taken. We meet still more frequently in practice Avith cases in Avhich the first doses of potassium iodide produce moderately severe nervous symp- toms, such as dizziness, palpitation of the heart, headache, and slight convulsive movements. It was probably cases like these which gave rise to the not very appropriate term "ivresse iodique," which is employed in France. The morbid phenomena which arise from a prolonged use of small doses of iodine or of potassium iodide, and are ordinarily comprised under the term iodism, consist of several groups of symptoms, which sometimes occur all together, and sometimes separately. That these symptoms do not exclusively belong to chronic iodism is sufficiently shown by Rose's case. We find them also in acute cases, where a single large dose of iodine has been taken into the organism, provided death does not ensue during the first violent attack of the poisoning. They are: 1. Nervous disturbances. 2. Derangements of digestion. 3. Affections of the mucous coats of the eye, nose, and throat, with anomalies of secretion. 4. Affections of the skin. 5. Atrophy of certain glandular organs. METALLOIDS.—IODINE. 303 The pathogenesis of the digestive derangements and of the impairment of the nutrition of the entire body dependent on them has been already discussed. The nervous derangements Avhich characterize iodism are exceedingly variable in form and intensity. By many authors their occurrence is positively denied. Frequently they are limited to the trifling symptoms of ivresse iodique referred to above. It is evident, however, from the communications of Wallace and Rodet,1 that they may at times attain dangerous proportions, since those observers have repeat- edly observed severe motor and mental disturbances of the character of general paralysis. A very frequent nervous symp- tom of iodism, according to both Ricord2 and Wallace, is neural- gic pains in the lower and anterior part of the left epigastrium. Wallace designates this symptom as pleurodynia; Ricord re- gards it as a neuralgic affection of the fundus ventriculi. Of the affections of the mucous membranes, the conjunctivi- tis, Avhich consists in reddening of the conjunctiva and marked increase in the secretion of tears, is often developed, according to Ricord, on the second or third day after the beginning of the iodine treatment. Paul Bernard 3 frequently saw it develop dur- ing the second or third month of the treatment. The affections of the mucous membranes of the nose and throat — the coryza and angina of iodism — are more common. Some authors state that salivation is a rare symptom of iodism, Avhile others have never met Avith it in this connection. It is said that it can be distinguished Avith certainty from mercurial salivation by the salty taste, and by the absence of fcetor ex ore, stomatitis and swelling of the glands. That the last symptom is not invariably wanting, is proved by Rose's case, in which the extreme salivation was accompanied by a mumps-like swelling of the glands. The iodine coryza is characterized by a copious secretion of watery mucus, moderate redness, and slight swelling of the nasal mucous membrane. In the angina the patients complain of intense itching in the throat, and not so much of difficulty in 1 Gaz. med. de Lyon. 1860. ? Gaz. med. de Paris. 1869. s These. Strasburg. 1863. 304 BOEHM.—POISONS. swallowing ; the posterior wall of the pharynx is deeply red- dened, and somewhat intumescent. The coryza is, as a rule, combined with a tolerably intense frontal headache. Sartisson (loc. cit.) has attempted to explain the pathogenesis of the affections of the mucous membranes in iodism. He suggests it as possible that potassium iodide, which is elimi- nated in the saliva and nasal mucus, may be decomposed by the carbonic acid and the chlorides in these secretions; the iodine which is thus set free could then act as a direct local irri- tant on the adjacent mucous membranes, and produce the coryza, the conjunctivitis, and the angina. The recent observations of Binz tend to support the theory of the occurrence of such decom- positions ; but still we cannot at once and unconditionally exclude the other possibility, that the disorders in question may originate in anomalies in the innervation of the blood-vessels and glands of those mucous membranes. The peculiar impair- ment of sensation in the mucous membranes in bromism is suf- ficiently analogous to render such a pathogenesis conceivable. Definite knowledge on this point can, however, only be attained by new researches and observations. The iodine exanthemata are variable in form, and appear in various localities. The form that is most commonly met with is an eruption of acne-like nodules on the skin of the face (fore- head, temples), neck, and the upper half of the thorax ; more rarely this extends also over the abdomen and extremities. Bazin' assumes three different forms of iodine exanthem. The mildest form is the erythematous, Avhich appears in the shape of more or less universal urticaria-like knobs. Out of this form the second, more common papular form is developed. The larger papules are surrounded by areolae, which are often confluent, and present a deep red color, vanishing for a moment on pressure. Finally, a pustular exanthema is sometimes devel- oped from the papular form ; it occurs in scattered spots on the face, thorax, and extremities. Occasionally a few of the pus- tules develop into small dermal abscesses. We'must, finally, make room here for the statement made by Mercier,' that Kuess, 1 L'Union med. 1866. 2 L'Union mad. I860, METALLOIDS.—IODINE. 30.3 in Strassburg, has not unfrequently met with oedema of the eye- lids, the skin of the abdomen and the forearms, in connection with iodism. Iodine exanthemata run their course without fever, and, like all the symptoms so far mentioned, vanish spontaneously when the remedy is discontinued. Before speaking of the atrophy of the mammae, we must, for the sake of completeness, mention the fact that Kuess is said to have frequently observed hemorrhages from the lungs during the employment of the iodine treatment; while on the other hand, in a feAv isolated cases, metrorrhagia or habitual increase of the periodic menstrual flow, has been demonstrated. It is generally admitted that the female breast is the only organ which may undergo complete atrophy as a result of the action of iodine. Hufeland first suggested, over fifty years ago, the possibility that atrophy of the testicles might also be produced by the iodine treatment; his idea found a ready acceptance, and was quoted so often by one author after another, that it gradu- ually and imperceptibly came to be accepted as a fact. It has I teen pointed out, however, that there is an absolute lack of observations which might serve to prove the influence of iodine in causing atrophy of the testicles. A similar statement cannot be made with regard to its action on the mammae. Although all authorities, and especially Ricord, agree that it is a very rare occurrence, still cases are constantly occurring from time to time, in which the atrophy of the mammary glands is unquestionably an effect of the iodine treatment. As yet we are entirely unable to understand this fact. It is, hoAvever, not more problematical than the analogous action of iodine in goitre, which at the pres- ent day is so generally admitted that it no longer causes aston- ishment. In the pathologico-anatomical connection, the cases of Rose and Hermann constitute almost the only sources from which we can draw information. The following are the most important points which can be deduced from them. Rose found free iodine in the stomach and alimentary canal, although originally the tincture had been injected into the cysts ; the mucous membrane was colored brown by it. The kidneys VOL. XVII.—20 306 BOEHM.—POISONS. also, on section, presented a brown color, which, gradually dis- appeared on exposure to the air. In the pelves of the kidneys there were slight hemorrhages ; the other organs were all normal. Hermann (internal poisoning by tincture of iodine) found the mucous membrane of the pharynx, epiglottis, and oesophagus covered in spots with an orange-yellow pseudo-membrane ; the spots were partly isolated and partly confluent. Beneath the false membranes the mucous coat was sAvelled and suppurating. In the stomach the coloration produced by the iodine was the only thing that could be discovered. In the present rudimentary state of our knowledge regarding acute iodine-poisoning, we possess but few special points on which a rational treatment can be based. Starch, and, according to Husemann, egg albumen, which is quite as efficient on account of its affinity (!) for iodine, may be used as antidotes. Aside from them, we must for the present rest contented with the fulfilment of all the symptomatic indications, which need not be here detailed. It is a question whether something might not be accomplished by the use of agents Avhich relax the muscular coat of the arteries, ex. gr., nitrite of amyl. The phenomena of chronic iodism can, as has already been mentioned, be relieved by suspending the iodine treatment. The disturbances of nutrition, the weakness, loss of flesh, and gastric disorders, which may remain behind, require a careful and ap- propriate strengthening treatment. CHAPTER Til. POISONING BY BROMINE AND ITS COMPOUNDS, ESPECIALLY POTAS SIUM BROMIDE (BROMISM). The toxicological importance of the bromine compounds de- pends principally on the therapeutic employment of potassium bromide, which, in spite of the contradictory statements of clinical authorities as to the value of the agent, is constantly becoming more extended. The poisonousness of elementary bromine and of some of its other compounds (hydrobromic acid, METALLOIDS.—BROMINE. 307 etc.), which has frequently been demonstrated experimentally, is of but slight importance to the practising physician, so long as those preparations are as little used as at present. We will, therefore, touch but briefly on poisoning by free bromine ; but both theoretically and practically the interesting poisoning by potassium bromide demands a more searching in- vestigation. Bromine is at ordinary temperatures a deep reddish-brown, heavy liquid (sp. gr. 2.97). When exposed to the air it gives off dense orange-yellow vapors, which are taken up with tolerable readiness by water, and impart to it the characteristic bromine odor and a yellow color. In its chemical relations it resembles chlorine and iodine. In the liquid form bromine is one of the most active corrosive poisons ; in the gaseous form, one of the most poisonous, irrespir- able gases. Balard, the discoverer of this element, and Berzelius drew attention to the deleterious action of bromine on animal and vegetable substances, which depends upon the strong affinity of the element for hydrogen, with which it unites to form hydro- bromic acid. In this way bromine decomposes the animal tis- sues, the coloring-matter of the blood and fat, and coagulates solutions of albumen. Glover1 found that if solutions of egg albumen were treated with a certain amount of bromine water, a coagulum was formed, but the yellow coloration of the bromine disappeared. On the skin, liquid bromine produces an intense yellow color- ation, blistering, and when its action is prolonged, deep eschars. Analogous effects are produced by the application of bromine to the mucous membranes. The symptoms of the acute gastro- enteritis which rapidly follows the introduction of the poison into the digestive tract are, however, somewhat complicated by the respiratory disturbances which are caused by the penetration into the air-passages of the bromine vapors developed in the body. Edinb. Med. and Surg. Journ No. 152. 1842. 308 BOEHM.—POISONS. Smaller doses, such as dilute aqueous solutions of the ele- ment, cause, as might be expected, less severe derangements ; they consist in a burning sensation in the oesophagus, pain in the epigastrium, salivation, nausea, vomiting, diarrhoea, and colicky pains. Besides these effects, which have been demonstrated by Glover J and Barthez,2 by experiments on animals, and by Hoe- ring, Butzke, Heiemerdinger,3 and Fournet,* by experiments on human subjects, Blake,6 Glover, and Barthez have also observed the phenomena produced by injecting pure bromine and bromine water into the veins of mammals. When pure bromine was employed, death ensued immediately, with tetanic spasms—evi- dently in consequence of instantaneous coagulation of the blood. The injection of bromine water also produces at first violent general spasms, which, however, cease in a few minutes, if the concentration of the bromine solution does not exceed a certain limit. In many of the animals experimented on by Glover and Barthez, coryza with violent sneezing and lachrymation was sub- sequently developed. The respiration and pulse were at first very much accelerated, but became gradually weak and slow; repeated vomiting, and evacuation of the bowels and bladder ensued. After small doses the animals gradually recovered from these symptoms ; after larger and fatal doses, the respiration finally became very labored, a bloody froth oozed from the mouth of the animal, violent general tremor set in; the heart's action ceased in from one-half to one and a half hours. The inhalation of bromine vapors causes the same phenomena as are produced by all irrespirable gases. In the milder grades of the poisoning they are the symptoms of irritation caused by the action of the gas on the sensitive nerves of the mucous mem- branes, and also reflex symptoms, viz., lachrymation and sali- vation, spasmodic contraction of the orbicularis palpebrarum, coryza, cough, and moderate oppression ; in the severer grades, besides the above-mentioned symptoms, a feeling of suffocation, 1 Vid. supra. 3 Hasselt-Henkel's Toxikol. 2 Cf. Frank's Magazine. I. p. 386 et seq. 4 Frank's Magazine, loc. cit. 5 Edinb. Med. and Surg. Journ. 1847. METALLOIDS.—BROMINE. 309 great anxiety, burning pain under the sternum, headache, dizzi- ness, and finally, when the bromine vapors have been very con- centrated, spasm of the glottis and asplryxia. Up to this time only a single case of internal poisoning by liquid bromine has been recorded in medical literature. The case was that of a man in New York, who took one ounce of the substance with suicidal intent.1 The result was of course fatal. Besides this, a case of quite serious external injury by liquid bromine is reported from the manufactory of iodine and bromine at Cherbourg. In consequence of the breaking of a stopcock in a vessel filled with bromine, two persons who were working with it were splashed with the substance as it escaped, and one of them sustained considerable injuries on the hands and forearms. The skin was entirely destroyed Avherever it had been touched by the poison, and several months elapsed before the patient recovered from the injury.2 No evidence can be adduced from the literature of the sub- ject to prove that the vapor of bromine exerts any serious in- jurious effects on the workmen who have to deal Avith that substance. In the text-books, it is true, we read of morbid affec- tions to which the workmen in bromine factories are frequently subjected — of a conjunctivitis and ebrietas e bromio — which Chevallier in particular is said to have described. We have not been able, however, to find anything like such a statement in the only article on the subject that has been published by Chevallier. That article consists principally of the letters of two manufacturers who, in response to Chevallier7 s inquiries, de- clare that their workmen suffer from no peculiar disorders. We might perhaps conclude from this, that the workmen are usually but little exposed to the poisonous vapors. In a case reported by Duffield the inhalation of concentrated bromine vapors pro- duced an attack of spasm of the glpttis which only yielded to prolonged inhalation of steam. The assumption of Diez3 that laborers in salt-mines are subject to a sort of necrosis of the 1 Reported by Snell, New York Med. Record. 1851. 1 Chevallier, Ann. d'hygiene. publ. 1842. 2. p. 313. 3 In Husemann, Toxicol. 310 BOEHM. —POISONS. lower jaw-bones, due to the action of bromine, has so far not found the confirmation which it greatly needs. In the treatment of cases of poisoning by bromine we are unable, on account of the scarcity of the observations at our dis- posal, to recommend anything more than a mere symptomatic treatment. Both the toxic and therapeutic actions of potassium bromide and of the other neutral bromine compounds, sodium, ammoni- um and calcium bromides, have of late years been very actively discussed, and the literature of the subject is consequently very abundant. Before we direct our attention to the details of the symptoms of poisoning, we must first briefly consider the important ques- tion whether the alkaline and earthy bromides, as such, have a specific action on the animal organism, or whether the bromine in these salts has no effect, their action being due entirely to the base present. An affirmative reply to the latter portion of this question has been given by a number of authors who have sought to establish the point principally by experiments on animals, while the spe- cific action of bromine is chiefly supported on the grounds of practical therapeutic experience. However, some clinical author- ities also have denied this specific action of bromine. Especially since the poisonous action of the potash salts has become gen- erally known, it has been repeatedly asserted that the therapeutic, as well as the toxic effects of potassium bromide, must be ascribed to the potash which it contains. It seems to us that these differences of opinion are not by any means irreconcilable, if we take into account the variety of the methods by which the discordant results of the different authors were obtained. It must in the first place be noted that the so-called bromism, the form of poisoning which occurs after the administration of potassium bromide, and is considered characteristic, has been observed only in human beings, and then only after prolonged use of the agent. It is not at all astonishing that experiments on animals, which are necessarily limited to a disproportion- ately shorter period of observation, should have afforded noth- METALLOIDS.—BROMINE. 311 ing analogous. In them, as is evident from the observations of almost all experimenters, only those little characteristic phenom- ena occur which we are accustomed to see after poisoning by the potash salts. There is an unquestionable similarity between the action of the potash salts in general and of potassium bromide in particular, especially on frogs, and, as far as the general phenomena are concerned, on mammals ; but still a closer analy- sis shows that even in the experiments on animals there is no positive identity in their action. Thus, Steinauer J very properly draws attention to the fact that Schouten's2 investigations on the blood-pressure by no means agree completely in their results with those obtained by similar experiments with other potassium salts. In the experiments on animals, it is true, the action of the potassium may always play the principal part, especially when the salt, as has been done by most experimenters, has been directly introduced into the circulation by injecti n into a vein. The phenomena of bromism, however, as they occur in men after the use of potassium bromide, must unquestionably be ascribed to the specific action of the bromine, if the statement recently made by Starck,3 should be confirmed. That observer found that the specific symptoms of bromine-poisoning (nervous de- rangements, exanthem) make their appearance in men after pro- tracted use of sodium bromide also. The analogous question whether the anti-epileptic and hyp- notic actions of potassium bromide are also to be referred to the bromine in the compound, of course cannot be settled here. Let us pass to the descrij)tion of the effects of potassium bromide on the animal organism. Regarding the chemical properties of the drug, it is enough to state that it is a neutral salt, which crystallizes in cubes, is 1 Virchow's Archiv. LIX. 1874. 2 Arch. d. Heilkunde. XII. 1871. We do not believe that the question has been set- tled by ScJiouUn's researches. On page 114 we read in leaded type .... "that the doses, which are used in therapeutics, in fact increase the frequency of the pulse, but at the same time diminish the blood-pressure" (unlike the other potash salts, which increase it). On the other hand, on page 116 he tells us that doses of potassium bromide, which do not endanger life, first cause an increase in the blood-pressure. Which, then, is the usual effect ? 3 Allg. Zeitschr. f. Psychiatric 1874. 312 BOEHM.—POISONS. readily soluble in water, and in its chief characteristics is analo- gous to the corresponding chlorine compound. The data concerning its conditions of absorption are given in detail in the work of Clarke and Amory;' according to them it is readily taken up by all the mucous membranes. When a moder- ate quantity dissolved in Avater is taken on an empty stomach, it is absorbed in about half an hour.2 The rectum absorbs the agent more slowly, but quite as surely, Avhile it is not taken up at all by the external skin. It is eliminated chiefly through the kidneys. The first traces of bromine, as early as ten minutes after the administration of the dose, are found in the urine. Rabuteau' asserts, however, that this excretion normally (with- out special administration) contains small traces of potassium bromide. The major part is removed from the body in the urine during the first twelve hours, though the elimination still continues after three days have elapsed. The assertion made in many hand-books, that after the administration of potassium bromide free bromine appears in the expired breath, lacks con- firmation entirely. The elimination of the substance through the external skin has been demonstrated by Bill4 and Bowditch.' The former found it in the water with which the skin was washed, the latter discovered it in the sweat, produced artifi- cially by a Turkish bath. Rabuteau also, after the internal administration of the salt, found bromine in the saliva and the nasal mucus ; Bill found the bromurets (Bromiire) in the secre- tion of the lungs, in the pharyngeal mucus, and in the faeces. With regard to what becomes of the salt in the organism, our knowledge is still somewhat incomplete. Clarke's supposition that the free acid of the gastric juice displaces the bromine from 1 The physiological and therapeutical action of the bromide of potassium, etc. Boston, 1872. 2 Since these authors believe that bromide of potassium is decomposed by the acid of the gastric juice and bromine thereby set free, they recommend that the salt should always be administered on an empty stomach (when the gastric secretion is neutral). They evidently forget that the solution of the salt itself may act as an irritant and excite the secretion of true gastric juice. 3 Gaz. hebdom. 1868. 4 Husemann in Virchow's and Hirsch's Jahresb. 1868 (Amer. Journ. of Med. ScL). 6 Ibid. Abstract from Boston Med. Journ. 1868. METALLOIDS.—BROMINE. 313 it, has not only not been proved by experiment, but as an hypo- thesis is in the highest degree improbable. We know, that even the iodine of the potassium iodide, a much more unstable com- pound, is not set free in the stomach. Binz,' moreover, has demonstrated that, unlike potassium iodide, the bromide cannot be decomposed by carbonic acid in presence of active oxygen, and he observes further that at a low temperature it is not decomposed even by nitric, nitrous, or hyponitric acid. In consideration of these facts it is hardly conceivable that the small quantity of the free acid in the stomach could exert a more powerful action on the potassium bromide. On the other hand, there is a considerable basis of probability for the assumption that a double decomposition takes place between the common salt, which is present in large quantities in the stomach, and the potassium bromide, as a result of which potassium chloride and sodium bromide are formed. In the urine the bromine appears combined with an alkali as a bromide, and accord- ing to the statements of Rabuteau, Bill, and BoAvditch, partly also as a bromuret (Bromiir).2 The form Avhich the potassium bromide assumes in the blood and tissues is still unknown. However, the effects of the salt on human subjects, as well as Binz's observations on the behavior of its congener, potassium iodide, renders it probable that the action of the bromine com- ponent is felt somewhere in the organism, unless, indeed, we 1 Deutsche Klinik. 1873. No. 48, and Virchow's Arch. LXII. 1874. 5 The terms Bromnr and Bromid of the German refer to the saturating capacity of the element with which it is combined, the lower saturating capacity being indicated bj the former termination—" iir." Thus, what was known as protobromide of mercury, corresponding to the chlorine compound generally known as calomel, would be Queck- silberbromur, the calomel being Quecksilberchlorur ; while the bromine compound cor- responding to corrosive-sublimate, perchloride or bichloride of mercury, would be QuecLsilberbromid, corresponding to Qiucksilberchlorid. AVhen an element forms only one series of compounds, as potassium, the terms ending in ilr and id are, by some, used indiscriminately. The same remark applies to the iodine compoimds lodiir and lodid, and to the oxygen compounds Oxydul and Oosyd, the presence of the u in the final syllable indicating the lower saturating capacity of the element. In the present chemical nomenclature a similar terminology is practiced, and we have ferrous and ferric compounds, mercurous and mercuric compounds, as well as nitrous and nitric or sulphurous and sulphuric acids, etc.—Translator's Note. 314 BOEHM.—POISONS. accept the theory of Steinauer (loc. cit.), who assumes that in those bromine compounds, in which the possibility of a separa- tion of the bromine is not given (among which he numbers potassium bromide), the substituted bromine-atom modifies the action of the other constituents (in this case potassium). The results of physiological researches on animals (frogs, rabbits, cats, dogs, etc.) have, as has been already stated, led the majority of the authorsx to the conviction that potassium bro- mide produces entirely the same effects as the other potash salts. These effects consist in their essence in a diminished activity or paralysis of the central nervous system, and paralysis of the heart, while the peripheral nerves and the striated muscular fibres are left unaffected by the poison. To avoid repetition, we refer the reader to the chapter on the potash salts for an account of the experimental data in question. From the study of the experimental works on potassium bro- mide, no other conclusion can be drawn than that the results obtained required to be identified with those of potassium- poisoning, if we put out of the question the as yet unexplained discrepancies which are contained in the work of Schouten. The facts adduced do not appear to us to warrant any further conclusions. The assumption of a disorder of nutrition and a diminution of the nutritive changes produced by potassium bro- mide, which emanated from Schouten, is evidently no more than an hypothesis. The behavior of the arterial vessels plays an important role in the experiments hitherto published. The majority of the authors2 assume, on the basis of numerous ob- servations of the retina of the eye, the vessels of the pia mater, the arteries of the mesentery, the ears of rabbits, and the web of frogs, that potassium bromide produces a contraction of the muscular coat of the vessels, and some few believe that the entire action of the poison on the nervous system can be ex- plained in this way. Considering the great unreliability of all 1 Eulenberg and Guttmann, Med. Centralbl. 1867.—Lewizky, Virch. Arch.—Damou- rette and Pelvet, Bull. gen. de therap. 1867.—Schouten., loc. cit., etc. 2 Lewizky, Saib-Mehmed, Clarke and Amory, Saison, Witchead, and Damourette and Pelvet. Others have either seen an immediate dilatation of the vessels (Nicol and Mos- sop, by observation of the retina), or dilatation following contraction. METALLOIDS. —BROMINE. 315 the methods of investigation hitherto employed, even without taking into account the dissenting statements made by other authors, we cannot attach much weight to the above observations. For the rest, even if its influence in causing contraction of the vessels could be positively proved, we should hardly attain there- by to a better understanding of the mode of action of potassium bromide. It is evident that these experimental results cannot explain the essence of those phenomena which result from a prolonged impregnation of the human organism with potassium bromide. They do not even allow us to conclude that the phenomena of bromism are produced by the potassium, so long as no one has demonstrated that for the production of this complex of symp- toms the prolonged administration of any other potash salt is sufficient. Very little consideration is necessary to show that the results of an experiment on an animal, which, apart from the different method of application, only extends over a few hours, cannot be compared with the state of affairs which results from feeding the human organism with the poison for weeks, often for months, and even for years. We must therefore, in dis- cussing bromism, entirely disregard these experimental results. The fact that manifestations of an affection of the central nervous system—namely, depression of the functions of the brain and spinal cord—have been observed both in the chronic poisoning by potassium bromide in men and in the experiments on animals, indicates that the above-mentioned organs are the chief points of attack for the action of the poison, not only in chronic and acute bromide-poisoning, but also in poisoning by the potassium salts. Bromism, or the form of intoxication produced in men by potassium bromide, arises, as has been already frequently stated, exclusively from the therapeutic use of this drug in va- rious nervous diseases. It is usually the result of a prolonged treatment, in which the remedy has been used in doses of from one to twenty grammes (from fifteen grains to five drachms) per diem for months or even years. In rare cases, however, bromism assumes the character of an acute poisoning, namely, when, as is so often the case in the 316 BOEHM.—POISONS. beginning of treatment with the preparations of iodine, the symp- toms of poisoning present themselves after the administration of only a few moderate doses. Thus, Johnson1 observed in several of his female patients. after the administration of the first small doses of potassium bromide, general tremor of the muscles, formication, and pare- tic phenomena, which lasted only a short time. Bowditch also (loc. cit.) saw, in a few cases, restlessness and nervous agitation follow the use of this substance. Labordes made experiments on himself to ascertain the action of single large doses (15 grammes =half an ounce). They caused at first a salty taste in the mouth, increased secretion of saliva, frequent eructations, and nausea. In an hour and a half nervous disturbance set in, which lasted for eighteen hours. Almost all of the functions of the central nervous system were to some extent affected. Depression of spirits, dizziness, disturbances of vision, somno- lence, and sleep with bad dreams, indicated a decided affection of the brain. The power of voluntary movements was greatly diminished, the gait was unsteady, and the tongue thick. Finally, he experienced also a decided blunting of sensibility and of reflex excitability. The power to resist the action of the drug varies very much in different individuals. Voisin* remarks that children bear exceedingly large doses (12 grammes [three drachms] per diem) without injury. In adults, of whom women are said to be in general more readily affected than men, the rapidity with which the phenomena of poisoning appear depends on the size of the daily dose of the bromide. Small doses of from 1 to 3 grammes (from fifteen to forty-five grains) per diem can be administered for months without injury. That this rule, however, is not with- out exception, is shown by Cholmely's * case, in which, although only from 1.8 to 2.7 grammes (from twenty-eight to forty-one grains) were given per diem, the bromine-rash made its appear - 1 Husemann in Jahrsber. of Virchow and Hirsch. 1868. 2 Gaz. med. de Paris. 1869. 3 Arch. gen. de med. XXI. 1873. 4 Bost. Med. Journ. 1869. METALLOIDS. —BROMINE. 317 ance. On the average, according to Starck,1 the symptoms of poisoning appear in the second or third week after the begin- ning of the treatment. Voisin2 expresses himself much less decidedly on this point. He states that bromism occurs in individuals who have been taking the drug daily in doses of from 4 to 10 grammes (from one to two and a half drachms) for several months or years, and that we are unable to explain why the symptoms show themselves earlier in one case and later in another. It is certainly not an unimportant point that the most of the individuals on whom bromism has hitherto been studied were not in a normal condition, but were, on the contrary, epileptics, whose entire systems, even before the beginning of the treatment, were in a state of profound disturbance. Starck mentions par- ticularly that he has seen the more serious forms of bromism almost exclusively in epileptics in whom the disease had existed for many years, and was associated with advanced psychical deterioration. The symptoms of bromism are composed of: 1. Disorders in the sphere of the central nervous system. 2. Anomalies of digestion and nutrition. 3. Affections of the skin. With reference to the pathogenesis of the clinical picture, in which sometimes one set of symptoms and sometimes another predominates, but little can be said. We might include the entire intoxication in the sphere of the so-called cumulative actions, but we are unable to determine whether it is necessary for the production of this toxic effect that a certain amount of the injurious agent should have accu- mulated and been retained in the organism. Voisin, at least, is of the opinion that the occurrence of bromism is connected with disorders in the action of the skin and the elimination of the poison from the body. At all events, it is a striking point that 1 Loc. cit. p. 72. The amount of bromine administered previous to the development of the bromism varied, for men, between 100 and 140 grammes (three and four and a half ounces); for women, between 40 and 110 grammes (one and one quarter and three and a half ounces). 2 Loc. cit. p. 51. 318 BOEHM. —POISONS. the resistance of the organism ordinarily ceases abruptly after the patient has taken the poison for a long time without detri- ment. The disorders of digestion and nutrition, which are generally developed gradually, are less difficult to explain. The cutaneous affection is connected by many authors with the elimination of the bromine through the glands of the skin, although absolute proof of its production in this way cannot be adduced. The phenomena do not follow any exact law in regard to the order in which they appear. Usually the nervous disturbances precede the development of the exanthem. With regard to the course, Voisin distinguishes an acute and a lingering, slow form; he also recognizes a bromine cachexia, which is characterized by a general decline of the nutrition. The detailed description of the symptoms presents some diffi- culties, since, in the observations reported by the writers on the subject, the majority of the patients were weak-minded ; and it is frequently impossible to determine exactly what symptoms are to be attributed to the primary disease, and what to the toxic action itself. As a rule, the symptoms of bromism develop with tolerable rapidity in the course of a few days, and without any prelimi- nary prodromal stage. They begin with subjective feelings of great exhaustion, weakness of the muscles, and vague pains through the whole body. The patients become depressed in spirits, listless, forgetful and apathetic, and have a reeling, extremely unsteady gait, and a thick, indistinct mode of speak- ing, associated sometimes even with partial amnesia. Single words fail them in conversation. Voisin cites an interesting case of a patient who manifested this striking disturbance of the memory also in writing: he wrote some words which were quite incomprehensible and other words only half-finished, in bewil- dering succession (agraphia). In higher degrees of bromism, absolute stupor supervenes with marked diminution of mobility. The patients then very frequently, at every attempt to move forward, fall down ; in other cases, still, the movements are ataxic, or attempts at movement provoke a general and prolonged trembling of the METALLOIDS.—BROMINE. 319 muscles. Voisin found that the sensitiveness of the skin was unchanged; consciousness also is never completely lost. The entire condition has by many authors been compared with the later stages of the general progressive paralysis of the in- sane. Voisin also asserts that there is another form of bromism which is characterized by paroxysms of insanity and delirium. Starck, on the other hand, believes that these symptoms, which are observed in epileptic patients, are not to be considered as due to the action of the potassium bromide, but must be explained by the checking of the epileptic fits. One of the most striking and most characteristic symptoms of bromism consists in the peculiar change in the reflex excit- ability of the palate and throat—a change, however, in which the sensibility of these parts does not participate. The reflex excitability of this circumscribed region is so completely sus- pended that even the roughest touch does not provoke the ordinarily active reflex contractions of the pharyngeal muscles. This remarkable fact, which Ave are still unable to explain, has been made use of recently in laryngoscopy. Bill observed, even after small doses of potassium bromide, a marked diminution in the sensitiveness of the mucous membrane of the urinary tract, and of the conjunctiva ; Gratumeau saw complete anaesthesia of the conjunctiva. In regard to the changes which take place in other parts of the body during bromism, these consist in more or less marked disturbances in the vegetative sphere : the patient has a bad appearance ; his face is of an earthy hue ; the expression is dull, and the mobility of the countenance is impaired ; the mucous membranes appear pale ; the excretion of saliva is sometimes increased, but more frequently the cavity of the mouth is dry, the breath ill-smelling, and the nose stopped by hardened secre- tion ; the weight of the body soon diminishes in consequence of a loss of appetite, and also sometimes as a result of an obstinate diarrhoea. In a few patients Voisin observed dyspnoea and an irritating croupy cough. The organs of circulation suffer during bromism from no especially characteristic derangements ; sometimes palpitations 320 BOEHM.—POISONS. are observed, and sometimes weakness and irregularity of the pulse, or decided retardation of the same. The temperature of the body is not sensibly affected. So far as the soporific action of potassium bromide and its effects on the sexual instinct are concerned, it seems to us that a discussion of these points is superfluous, since the above-mentioned effects are chiefly observed after small non-poisonous doses. The exanthemata, which belong among the most constant symptoms of bromism, arise at times independently of the above described neuropathic symptoms, at others in conjunction with them. They manifest themselves during the first two to four weeks after the commencement of the bromine treatment, last, as a rule, about a week, and then disappear independently of the fact whether the bromine treatment is maintained or interrupted. They occur, according to the united testimony of authors on the subject, in 60 per cent, of all cases where the bromine treat- ment is carried out (in men more frequently than in women). Starck, moreover, declares that the affections of the skin ordi- narily occur sooner in the female sex (after from fourteen to twenty-one days) than in the male (from thirty-three to forty-six days). The exanthem, as a rule, assumes one of the forms of acne, and consists of discrete (never confluent), dark reddish blotches, which attain the size of small-pox pustules, and like them, at a later stage, show a depression in the centre, and suppurate. They heal, leaving a dark-colored spot on the skin. Neumann,1 avIio examined the affection very closely, found inflammation of the glands of the skin with swelling of the cells of the cutis vera, and increase in size of the papillae. The exan- them is usually confined to the face, and especially to the region of the brow, mouth, and nose ; it appears less frequently on the cheek, neck, breast, and back. The affection is neither painful nor combined with itching, and runs its course without fever. In rare cases the skin disease occurs in the form of ery- thema, urticaria, eczema, ecthyma or furunculous formations, as appears from the observations of Voisin and Wood ;2 Turnbull 1 Wien. med. Wochenschr. 1874. 2 Brit. Med. Journ. 1871. METALLOIDS.—BROMINE. 321 and Witchead l noticed similar phenomena, and Neumann ob- served in an adult, who had been taking potassium bromide for a period of nine months, furuncles on that portion of the face which is covered with hair. The course and termination of bromism depend particularly upon whether or not the administration of the poison is disconti- nued at once upon the occurrence of toxic effects. If the drug be discontinued at the right time, /. e., as soon as possible, the phenomena under consideration usually cease with tolerable rapidity and without permanent injury to the patient; at most there will remain indefinite, unpleasant sensations, wandering pains, and general debility, which noAv and then persist for some time. Instances, however, are on record where treatment with bromine has produced fatal results. Such cases have been described by Hameau2 and Falret.3 Death ensued suddenly with phenomena of asphyxia, apparently from paralysis of the heart or of the nerve-centres. It is not our province, as we believe, to discuss the unfavor- able effects upon the course of the disease, and even upon the patient's life, which sometimes follow a suspension of the bro- mine treatment in cases of epilepsy. Still, the remark may here be made that Starck, who is occupied with comparative experi- ments on the action of sodium bromide and potassium chloride, has up to this time observed a single case where, after the use of five grammes (four scruples) of sodium bromide per day for three weeks, bromism developed in the most unmistakable manner, with the skin affection, etc. In most cases it suffices, in treating bromism, to intermit the use of the drug at once on the development of toxic symptoms, whereupon they cease of themselves ; at the same time it is well to supplement this treatment by a strengthening diet, frequent warm baths, and other diaphoretic procedures, as suggested by Voisin. Specific antidotes and other means of combating bromism are not known. 1 Quoted by Starck, loc. cit. 2 Journ. de Bord. 1868. 3 Quoted by Starck, loc. cit. VOL. XVII.—21 322 BOEHM.—POISONS. SECOND DIVISION. Poisoning by Acids. A. Mineral Acids. CHAPTER I. POISONING BY SULPHURIC ACID (SULPHOXYSM). Sulphuric acid (acidum sulphuricum, S03) is well known as one of the most powerful acids, and is noted for its strong affin- ity for water. When the concentrated acid is mixed with water, the commingling of the two is accompanied by an extraordinary rise in temperature. Sulphuric acid is odorless, gives off no fumes at ordinary temperatures, and, even when highly diluted, tastes exceedingly acid. Since it finds various applications in technology and trade, and is ordered in various preparations as a medicine, it may also cause poisoning in various forms. The ordinary oil of vitriol (English, or Nordhausen,1 sulphuric acid, acidum sulphuricum crudum), as well as diluted sulphuric acid, —frequently called "oleum" in common parlance, and diluted with water in the proportion of 1:5,—indigo sulphate solution, Haller's acid (Elixir, acid. Halleri), etc., are therefore the prep- arations which come under the cognizance of toxicologists. The nature of this poison is such that the greatest importance attaches to the effects of its immediate contact with the parts, Avhile the more remote effects which follow its absorption into the blood, as in the case of other poisons, remain in the back- ground, and but seldom come under observation. The chief characteristic, therefore, of sulphuric acid poisoning, is its local 1 The ordinary oil of vitriol (H2SO,) is generally known on the continent as " English sulphuric acid." The Nordhausen acid is called by chemists " fuming sulphuric acid," and consists of H2S04.S03 (=H2S,0,)—old system H0.2 S03* The two are not iden- tical, as would seem to be here implied.—Translator's Note. MINERAL ACIDS.—SULPHURIC ACID. 323 action, and it is only recently that absolute proofs have been adduced, which show that the acid can find its way into the blood by absorption, and there produce still other results. What happens, then, in the first place, when sulphuric acid comes in contact with organic tissues, and particularly with those belonging to the human body ? The acid satisfies its affin- ity for water by withdrawing it from the tissues, and the activity with which this takes place is in direct proportion to the degree of concentration of the acid. Simultaneously the tissues, under its influence, become profoundly disorganized ; for the acid not only takes up the bases contained in them and which are con- bined with weaker acids, but also dissolves everything that it comes in contact with, thus destroying the continuity of the tis- sue. Not one of the tissues belonging to the living organism has power to offer resistance to the action of sulphuric acid. Falck and Victor1 have made very accurate researches with respect to the action of sulphuric acid on various tissues. In solutions of albumen, sulphuric acid of any degree of concentration above a specific gravity of 1.250 causes precipitates, which dissolve completely in an excess of the acid. Less concentrated dilutions of the acid precipitate albumen but slowly. In defibrinated blood also the acid throws down a precipitate, which is soluble in an excess of the reagent, the blood being at the same time blackened. Fibrin suspended in water dissolves in an acid which has a specific gravity of 1.470, the solution assuming a yellowish-brown color; in less concentrated dilutions it remains unaltered. Muscular tissue is most readily dissolved by sulphuric acid of specific gravity 1.574 to 1.789, the solution assuming a blackish-red color, and the muscle first swelling up into a jelly-like mass. Dilutions of the acid having a lower specific gravity than 1.574 do not dissolve muscular tissue completely, but only dissolve the areolar tissue within it; the entire mass is first turned to a whitish hue, and then converted into a pap which is more or less thick. Tiie coats of the hog's stomach are completely dissolved within less than twenty- four hours in acid of specific gravity 1.470, the resulting slimy mass being of a blackish-brown color. In acids of a higher or lower degree of concentration, solu- tion takes place more slowly, or even, in very weak dilutions, not at all. The chemical products of decomposition which result from the action of sulphuric acid on the tissues are not accurately known. According to Mulder,2 in the tissue decomposed by the 1 Deutsche Klinik. 1864. Nos. 1-32. 2 Cf. Buchheim, Arzneimittellehre. II. Aufl. 1859. p. 180. 324 BOEHM. —POISONS. acid only ammonic sulphate and humic acid, together with free sulphuric acid, can be found. The question as to the form in which sulphuric acid is taken into the blood, after introduction into the stomachs of men or animals, has not yet been definitely determined. The possibility of the existence of free sulphuric acid, as such, in the blood of a living man, has already been disproved defi- nitely by Pereira and Buchheim.1 The acid reaction of the blood, observed by other authors (Walker,2 Hoelder,3 Casper4) in human victims of sulphoxysm, is considered by Mannkopf5 as a post-mortem condition, for he himself proved the normal alkaline reaction of the blood in cases of living men who had been poisoned by sulphuric acid. But inasmuch as recently, in many cases of sulphuric acid poisoning, the increased elimina- tion of sulphates in the urine has been demonstrated with abso- lute certainty, which implies incontestably an actual absorption of sulphuric acid, nothing remains but to assume either a satura- tion of the acid immediately after its absorption into the blood, or its absorption in the form of sulphates which haAre already been formed in the stomach or the tissues (Mannkopf [loc. cit.] and others). Improbable as it may appear, d priori, that the acid absorbed is neutralized in the blood, further researches are necessary to decide this point in one way or the other. As regards the elimination from the organism of the sul- phuric acid absorbed, it may be considered as settled that the acid leaves the body in the form of sulphates (Schultzen,8 Mann- kopf [loc. cit.]),T which appear in the urine in large quantities, chiefly as lime salts. Although this fact has in general terms been long since established (Orfila), it is only recently that it has 1 J. Pereira1 s Handbuch der Heilmitellehre, nach dem Standpunkte der deutschen Medicin bearbeitet von R. Buchheim. Leipzig, 1846. I. Bd. S. 449. 2 Monthly Journ. Vol. X. 3 Wiirtemburg Med. Corresp.-Blatt. 1852. 4 Handbuch der gerichtl. Medicin. 5 Aufl. II. 5 Beitrag zur Lehre von der Schwefelsaurevergiftung. Wiener med. Wochenschr. 1862 and 1863. 6 Arch. f. Anat. u. Physiol. 1864. '' According to Husemann (loc. cit., p. 7G1), Letheby and Miguel have also proved, by examinations of the urine, the elimination of sulphuric acid through the kidneys. MINERAL ACIDS.—SULPHURIC ACID. 325 received the attention which it deserves. It has been found that this elimination in the urine does not continue for a long time ; that in the beginning of a case of poisoning this elimination of the sulphates falls from a maximum to zero in a very short time ; one has, therefore, no right to infer, from the absence of sul- phuric acid in the urine in an acute case, that a state of poison- ing by sulphuric acid does not in that particular case exist. The urine in sulphoxysm is, as a rule, acid ; but whether it is so from the presence of other free acids, which have been deprived of their bases by the sulphuric acid, remains yet to be proved. Since such acids, according to this theory, must have formed already in the blood, the alkaline reaction of this fluid is at least not in accord with such an assumption. Recent observations have shed some light upon the changes which the sulphates circulating in the blood provoke in the organs of the body (Munk and Ley den, Mannkopf). The kid- neys, as it appears, are specially affected; they are thrown into an actual state of inflammation, which manifests itself during life by albuminuria and the presence of fibrinous cylinders in the urine, and, after death, by corresponding post-mortem appear- ances. Mannkopf holds that a direct irritation of the parenchyma of the kidneys by the sulphates is probable, and remarks that even Glauber's salts, when their laxative effects are prevented by the use of astringents, exert an irritating effect upon the kidneys, causing diuresis, and—in the case of already existing nephritis—aggravat- ing the symptoms. At the same time, however, and quite properly, he declares that these questions cannot be definitely settled until further experiments shall have been carried out. Cases of poisoning by sulphuric acid belong to the more fre- quent forms of poisoning which are met with by the practising physician. The reasons for this lie in the accessibility of the poison, and in the widespread, though very superficial knowledge of the effects which it is sure to produce. At the same time, cases of this form of poisoning do not appear to occur with equal frequency in all countries and localities ; at all events, certain places, among which is Berlin, furnish a disproportionately large quota. In the larger number of cases sulphuric acid is used for sui- 326 BOEIIM. —POISONS. cidal purposes, and this occurs very often among individuals of the lower classes, as, for instance, domestics, mechanics, etc. Next come, in the order of their frequency, the cases of acci- dental poisoning by this substance. These are mostly caused by ^ mistaking the acid for some beverage, an accident which has happened to sober persons, and also to those avIio Avere drunk. In a few cases, strange to relate, sulphuric acid has, by mistake, been used in clysters in the place of oil, the error leading to fatal results, as might be supposed. Sulphuric acid can only be administered with murderous intent to children, and those overcome by heavy sleep or drunk- enness. In the case of children, as the literature of the subject informs us, this has occurred often enough ; but only isolated cases are knoAvn where the acid has been administered Avith mur- derous intent to adults while asleep or overcome by the effects of alcohol. Christisonx relates that, in the large English manufacturing towns, the crime of throwing sulphuric acid upon a person's face, with the intent of causing mutilation, was not long ago so common that it Avas declared by parliament to be a capital offence ; and von Hasselt3 states that attempts at murder have been made by pouring the acid into the ear" of the sleeping victim. It is difficult to give exact statistics in regard to the frequency of sulphuric acid poisoning. Of 930 cases of poisoning observed in England, France, and Denmark, 190 were caused by sulphuric acid.3 Of 527 fatal cases of poisoning which occur- red in England during the years 1837 and 1838, only 32 were caused by sulphuric acid. In the Vienna General Hospital the cases of sulphuric acid poisoning consti- tuted nearly one-half (13 out of 30) of all the cases of poisoning which were observed in that institution in the years 1856 to 1858. According to Casper, nine- tenths of all cases of poisoning in Berlin are caused by taking sulphuric acid. Flandin found, among 180 cases of poisoning that occurred between the years 1841 and 1844, only 11 cases of sulphuric acid poisoning, from which it seems that this form of poisoning occurs more rarely in France than in other countries. Moreover, from the figures quoted, which are taken from Husemanii's Toxicology,4 no general conclusion can be drawn other than that sulphuric acid is to be reckoned among the poisons which are very frequently used. 1 Loc. cit. p. 160 [German edition]. 3 Cf. von Hasselt, loc. cit. L. c. p. 166. 4 L. c. pp. 353 and 759. MINERAL ACIDS.—SULPHURIC ACID. 327 We oursolves have collected, from the literature of the last fifty years, accounts of 113 well-authenticated cases of sulphoxysm. Of these 37, or 32.7 per cent., were men; 55, or 47.7 per cent, were women ; and 21, or 19.6 per cent, children under ten years. Of these, 77, or 68.2 per cent, resulted fatally, while 36, or 31.8 per cent., resulted in recovery. From these figures, it appears that there is a marked predomi- nance of cases among females, a point to which other authors have already called attention. The causes we could only ascertain with certainty in 53 cases : of these 21 were accidental, 16 suicidal, and 13 were cases of murder (children). As regards the amount of the poison which is requisite for poisoning with a fatal result (dosis letalis), in our opinion no figures can be given which will hold good for all cases. In deciding this point we must have reference solely to the results of practical experience, since the experiments on animals, in other respects so valuable, in this particular case can justify no conclusions with regard to mankind. But in this connec- tion nothing certain can be inferred from the records of cases of sulphoxysm. It very rarely happens that the amount of the poison used can be accurately estimated, and frequently one is also in the dark as to the degree of concentration of the preparation used. Besides, cases have been seen to end fatally, in Avhich it was known that small amounts of the poison had been taken ; and others have recovered where it was ascertained beyond a doubt that large amounts of concentrated acid had been taken. Much depends, as will be readily understood, on the amount of solids and fluids contained in the stomach. It makes a great difference also, as regards the course of the illness, whether the case comes under medical treatment early or late. Finally, not a little depends on the part of the body to which the poison was applied; those cases, for instance, where the poison was injected into the rectum, quickly ended in death. In general, it may be laid down as a rule that any appreciable amount of concentrated acid can produce death; at the same time, external circumstances have an important bearing on the issue, and we do not believe that any more precise rule can be formulated. The general character of the symptoms Avhich should occur after poisoning by sulphuric acid may be at least inferred, a priori, from Avhat has been said above. Still, it would be an 328 BOEHM.—POISONS. error to expect that all these symptoms Avould show themselves in every case. Individual idiosyncrasies, and, still more, chance assert their sway here ; and though the general features of the disease are in the main the same, yet a closer study of the litera- ture shows that the individual symptoms may vary greatly in character and intensity. These symptoms are not merely the immediate consequences of the local alteration of the tissues; they are due in large part to the reaction of the entire nervous system from the violent irritation communicated to it by the sen- sory nerves in those portions of the body Avhich have been sub- jected to the action of the acid. Then, besides, we must take into account the general phenomena caused by the absorption of the poison. Finally, we encounter numerous modifications of the usual complex of symptoms, as soon as the sulphoxysm passes from the acute into the chronic stage. As in these cases, how- ever, there can no longer be any question of a continued action of the poison, but rather of the consequences of the first moment- ary action, one might very properly think it advisable to discuss these cases in another department of pathology. Nevertheless, there are practical considerations which will not allow us to pass the subject over in silence, especially since, if we were to do so, the practitioner might in some cases be left in doubt in regard to the diagnosis and proper mode of treatment. The first scene in a case of sulphuric acid poisoning will vary according to whether the poison has been taken for a suicidal purpose, or has come into the patient's hands by an unlucky accident. In the former case, as a rule, the individual will natu- rally have swallowed a large amount of the poison, while in the latter case the quite unexpected pains and reflex actions which occur at the moment when the acid comes in contact with the parts, will usually cause a sudden expulsion of the poison. It is only in cases where a person, while intoxicated, has mistaken sulphuric acid for some beverage, and, while laboring under this belief, has taken the fluid doAvn as it were at a single gulp, that large amounts of the poison have found their way into the stomach. On the other hand, accidental poisoning involves more risk of the poison entering or coming in contact with the air- passages. MINERAL ACIDS.—SULPHURIC ACID. 329 The severity of the affection of the cavity of the mouth will therefore vary in accordance with the manner in which the poi- son has been taken. The contact of the acid with the mucous lining of the mouth causes a violent and sudden sensation of pain, which varies in severity according to the concentration of the acid, and is designated by the patient sometimes simply as a burning sensation, sometimes as a powerful drawing to- gether of all the parts, combined with an acid taste. If no acid has been swallowed, the subjective phenomena mentioned are limited to the organs of the cavities of the mouth and throat, Avhich almost immediately after the action of the acid show a whitish appearance.1 If the acid, however, has been swallowed, whether in small or in considerable amounts, the burning pains extend from the mouth to the stomach, and often spread from these rapidly throughout the whole abdomen. In the course of a very few minutes vomiting and violent retching ensue, black bloody masses being sometimes thrown up in large quantities. Frequently at this stage the patients suddenly fall down sense- less, and especially delicate individuals (women) are very apt to be seized with trismus and general tetanic convulsions, which are to be considered as reflex phenomena produced by the vio- lent pain. Death may occur at this stage—that is, a few minutes after the poisoning has taken place ; it is then brought about either by the powerful action of the poison upon the system, or by asphyxia due to a direct lesion of the air-passages by the acid. If very concentrated acid has been taken into an empty stomach, the immediate perforation of the stomach and the escape of the poison into the cavity of the peritoneum may be followed by death more or less speedily. As a rule, however, the affection pursues a less rapid course. Other phenomena are likely to appear before death relieves the patient of the inexpressible torture in which he has been during a period of several hours. The intensity of the local pains increases ; there is also a distressing difficulty in swallowing; and, Avith a raging thirst, the patient is yet unable to get down a 1 " As if sprinkled with salep powder" (Taylor). 330 BOEHM.—POISONS. single drop. Every attempt at swallowing brings on a fresh attack of vomiting and retching. In some cases there is continu- ous vomiting. At the same time, complete aphonia is often present, and there is almost always copious salivation. The external appearance of the patient is that of a person in a severe and general collapse. The eyeballs are sunk deep in their sockets, the eyes have a staring expression, and the pupils are dilated. The pale skin has a death-like coldness, and is covered with a cold, clammy sweat, while the skin of the face appears much reddened and greatly bloated. The thread-like pulse is frequent, and, as a rule, can be felt only with difficulty; the respiration, according as the air-passages are more or less directly involved, is more or less labored. The alvine and renal secre- tions are, as a rule, suppressed ; only occasionally has diarrhoea been observed, Avith or without blood, or a spontaneous discharge of urine containing blood or albumen. So far as the operations of the mind are concerned, most patients manifest great depres- sion of spirits, and in all their replies to inquiries, the most pro- found anxiety is observable. Others will be found, either at times or constantly, in a state of unconsciousness or stupor. In many cases of sulphuric acid poisoning, death ensues in the course of the first twenty-four to thirty-six hours, often after shreds of mucous membrane, which have become detached through the corrosive action of the acid, have been expelled by vomiting or per anum. These fatal cases, however, differ very much in their external manifestations. Either the unconscious- ness passes gradually into coma, and death ends the rapidly increasing collapse, or severe tetanic convulsions precede the fatal issue, as in death by suffocation. In the former case, we are very likely to find afterwards that the stomach was perforated, in which event the vomiting ordinarily ceases altogether some time before death; but in many cases we find ourselves unable to assign any other immediate cause for death, except the exhaustion of the individual's strength from the effects of the powerful strain upon the entire organism. Where the mode of death resembles that from asphyxia, with violent convulsions, Ave may, as a rule, attribute this result to local changes that have taken place with greater or less rapidity at the entrance of the MINERAL ACIDS.—SULPHURIC ACID. 331 air-passages (for instance, oedema of the glottis), in consequence of some of the acid having found its way to these parts. If the patient, during the time specified, does not succumb to the action of the poison, phenomena of reaction, both local and general, soon appear; the pulse, Avhich was weak before, becomes stronger, the temperature rises, and all the usual symptoms of an inflammatory fever manifest themselves. At those spots where the poison exerts its caustic action, the parts become red and swollen (from serous infiltration), purulent inflammation gradually sets in, and ulcers develop. These pro- cesses become neAv sources of torturing pain to the patient. In the cavity of the mouth there is often an enormous swelling of the entire mucous membrane, especially of the tongue, in conse- quence of which it is almost impossible to introduce food into the stomach; and if the posterior portions of the pharynx are involved, there will also probably be more or less dyspnoea. The difficulty in swallowing of course continues; and when, as Mann- kopf (loc. cit.) remarks, the eschar first separates from the walls of the mouth and throat, leaving behind a raw surface deprived of its protecting epithelial layer and highly sensitive, this diffi- culty is greatly enhanced. Salivation also continues, and the saliva flows constantly from the mouth of the patient. The region of the larynx is extremely sensitive to external pressure, an indication that inflammatory changes are also going on in its interior. Throughout the whole length of the oesophagus violent pains are felt, and retching and vomiting are the only response to the patient's attempts to swallow anything. The abdomen, Avhich is usually in a state of distention, is very sensitive to pressure, and the excretions from the bowels and kidneys are, as a rule, still suppressed. Only in rare cases has diarrhoea with dysenteric stools been observed. In the urine, passed naturally or by artificial aid, very large amounts of albumen and casts have recently been detected (Wyss, Mannkopf, Munk and Ley- den, and others). Still, albuminuria has not as yet been recog- nized by all observers as a constant symptom of acute sulphuric acid poisoning.1 1 Smoler found albuminuria but once in fourteen cases. Wiener Medicin. Halle, 1861. 332 BOEHM.—POISONS. Of course, even in this reactive stage of sulphoxysm, the duration of which cannot be exactly defined, the life of the patient is still in great danger, and, in fact, death frequently ensues in the course of the first week after the poisoning, though cases have often been known where,—especially when the action of the poison has been less energetic,—after this lapse of time, the patient was already far on the way towards recovery. In most cases recovery takes place slowly. It is indicated by a gradual decrease in severity of all the symptoms. The diffi- culty in SAvallowing, the pains, and also the vomiting, often last, however, for weeks. Fragments of mortified tissue, having an exceedingly foul odor, are repeatedly voided, either with the stools or with the matters vomited. A number of cases are on record where, after the lapse of several weeks, long tubes of detached (necrosed) mucous membrane were thus removed from the organism ; in two cases (Wyss,' Trier2), for instance, the en- tire mucous lining of the oesophagus came away in this manner. At this stage one often observes a symptom which closely resem- bles the globus hystericus : in attempting to swallow, the patient experiences a feeling as if a ball rose and fell in the throat. Recently, Mannkopf has further observed, in several cases of poisoning, neuralgic affections of the intercostal and abdominal nerves; also, in isolated cases, extended and severe hypersesthesia over the whole trunk, symptoms regarding whose pathogenesis we are as yet entirely in the dark. In the different cases they developed at different times, between the eighth and the twenty- second day after the poisoning. In this stage, also, the cicatrization of the parts destroyed by the corrosive action of the acid takes place, a process which, in the case of the mouth and pharynx, we can readily observe throughout its entire course. It is this process, too, which after the lapse of months brings the patient, who has successfully passed through all the other stages of the poisoning, face to face with death from starvation. In all such cases we have to deal with cicatricial strictures, which may be located in different por- tions of the alimentary canal. They form mostly at the inferior 1 Arch. d. Heilkunde. 1869. * Schmidt's Jahrb. 1852. MINERAL ACIDS.—SULPHURIC ACID. 333 portions of the oesophagus, less frequently in the superior por- tions ; they also form in the cardiac, but especially in the pyloric region of the stomach. In the latter case, proliferation of the tissues has been sometimes observed simultaneously with the stricture, and some authorities even report the development of a scirrhous groAvth from this proliferating portion. If the stricture has its seat in the oesophagus, or at the cardia, the food taken will, as a rule, be regurgitated before it can reach the stomach, If the contraction, however, is at the pylorus, the food which has been received into the stomach will be vomited up, either at once or after some time has elapsed. The natural consequence of such alterations of the tissues in the organs of digestion is a slowly progressing inanition, from the effects of which the patient, emaciated to a mere skeleton, ultimately dies. It is worthy of note that these strictures sometimes first develop after the patient already regards himself as entirely cured, and even after he has been able for a considerable period to take food without any difficulty. The tardy development of a stricture in such cases is due to the presence of an ulcer which cicatrizes but slowly. As a matter of course, in a treatise like this, all the phe- nomena which have been observed in the numerous interesting cases of sulphuric acid poisoning recorded in literature cannot be described in detail. Fistulous communications of all con- ceivable kinds can form between different organs ; and, among other things, suppurative parotitis, and paralysis of the sphinc- ter ani, with incontinentia alvi, have been observed As regards the external appearance of the corpses of persons who have succumbed to acute sulphoxysm, they present but little that is characteristic. The observation has been made that they resist decomposition for an extraordinary length of time, which Casper is inclined to refer to the neutralization of the am- monia formed by decomposition. At the present time we pos- sess no facts which would corroborate this hypothesis, or which would justify us in bringing forward any other. On the external skin, Avherever the acid comes in contact Avith it, changes will be found which extend to a greater or less depth, according to the 334 BOEHM. —POISONS. degree of concentration of the acid. According to the statements of different authors, it is a very common occurrence to find rib- bon-like streaks extending from the corners of the mouth a variable distance downward or outward, on the line of which the epidermis shows a dirty yellowish coloration and a parchment- like consistence. Besides this, one often observes, at various places on the external skin, brownish or rust-colored spots, cov- ered with crusts, beneath which a reddened and often ecchy- mosed tissue is found. These different changes, of course, rep- resent various grades and stages of local corrosive action. The lips are usually altered in a similar manner, though often they are quite intact. In the cavity of the mouth the changes observed Avill be the same as those which are seen during life, '/. e., a yellowish-white coloration of the epithelium, which may be lifted off in large patches, and beneath which the tissue ap- pears, at times, only reddened, at others of a dirty color, and at others still mortified or infiltrated Avith pus. Ulcers are met with in all stages, up to complete cicatrization, in the cavity of the mouth, upon the walls of the pharynx, upon the epiglottis, and in the interior of the larynx. An analogous state of things will be found in the oesophagus, which usually appears strikingly small and thrown into folds, and is deprived of its mucous cov- ering to a greater or less extent. The stomach, if concentrated acid has acted upon it, as a rule is noticeably changed, even in external appearance ; the outer surface displays, instead of its natural color, a deep black hue. The tissue of the organ is often in the highest degree tender and friable, and may fall apart when only touched with the forceps; at other times it is tough like parchment. On the inside the Avails of the stomach are found to be in all possible stages of disorganization, from simple erosion of the epithelium to perforation, and even to a conversion of the tis- sues into a blackish-brown, slimy mass. The contents of the stomach, which very frequently, though not always, manifest a strongly acid reaction, consist chiefly of dark masses which re- semble coffee-grounds, and which vary both in bulk and in con- sistence. In less severe cases the discoloration is not so decided, and ulcers are found in varying numbers. In cases of perforation of the stomach the abdominal cavity is more or less filled with MINERAL ACIDS.—SULPHURIC ACID. 335 the blackish-brown contents of the stomach, which also usuallv manifest a strongly acid reaction, and alter the other organs in the abdomen to a variable extent. The convex surface of the liver is sometimes found to be discolored and altered to the depth of several lines. Its appearance has been compared by some to that of a pyogenic membrane,1 and microscopically the liver-cells are found to be disorganized even to their nuclei. In the intes- tinal canal—should the acid pass as far down as this—phenomena analogous to those observed in the stomach are to be found. In isolated cases—and then only Avhen the stomach has been per- forated—the colon and other intestinal convolutions have been found to be perforated, apparently in consequence of the action (on their external surface) of the acid contents that have escaped from the stomach. Recently the liver has been found in a state of fatty degeneration, the kidneys in that of parenchymatous nephritis. The respiratory and circulatory organs seldom sIioav anything abnormal, nor do those of the central nervous system. In rare cases the arteries and veins have been found exten- sively filled with firm clots. The blood is said to show usually a tarry consistence and black color. It has already been noted above that during life its reaction is not acid, and that if an acid reaction be found after death, it is probably to be considered as a cadaveric change. If death ensues in a later stage of poisoning, cicatrices will be found in different places, and strictures, especially in the oeso- phagus and stomach. It has already been stated that these develop by preference at certain localities. As regards their structure, they are mostly fibrous, though in a few cases they have been found to contain cartilage. Above the stricture the lumen of the oesophagus is usually dilated, but beloAv, it is strongly contracted. For the rest, in such corpses Ave find every - Avhere the indications of a high degree of inanition, such as general lack of fatty tissue, atrophy of the muscles, etc. The prognosis in all cases of sulphuric acid poisoning is doubtful, in many cases absolutely bad. The treatment has for its chief task to render the poison in- ' Case of Wardens, Brit. Med. Jour. Sept. 1869. 336 BOEHM. —POISONS. nocuous. Though this appears, d priori, so simple, and though a whole series of true antidotes are so easily obtainable, we nevertheless cannot count with any assurance upon neutralizing the effects of the poison. The reason for this lies in the facts: first, that this poison is exceedingly rapid in its action; and secondly, that there is such marked difficulty in swallowing. Of course, emetics are not to be thought of in a condition where vomiting belongs among the most prominent symptoms. We can therefore only take into consideration the application of sub- stances which can neutralize the effects of the acid. There has been a good deal of discussion over the advisability of administering the different alkalies as antidotes ; many have even recommended large quantities of pure spring water as the best remedy, basing this advice upon the favorable results which, in a few cases, followed the immediate drinking of plentiful draughts of water,1 and also upon the assumption that by this means the sulphuric acid is prevented from withdrawing water from the tissues. In the first place, we must agree with Husemann 2 when he asserts that the nearest remedy is the best. Everything depends on neutralizing the poison with the greatest possible promptness. Every moment of culpable delay is, therefore, to be reckoned as an error. Such alkalies as are to be found in every house—chalk, soap, ashes, or whatever of that nature may come to hand—must be employed at once, while waiting for the prescribed remedies to arrive from the apothecary's. Of the officinal alkalies calcined magnesia is best suited for the purpose. The carbonated alkalies should not be employed where they can possibly be avoided, on account of the active development of gas which follows their administration, and moreover, because they also have a slightly caustic action, and are only converted into sulphates in the presence of large quantities of water." We do not think it necessary to discuss this question further, since no valid objection can be raised to the employment of 1 Fischer, Preuss. Vereinszeitung. 1849, * Loc. cit. p 765. 2 Luedike, Ueber die Gegengifte der Schwefelsiiure Preussische Vereinszeitung. 1839. No. 45 MINERAL ACIDS.—HYDROCHLORIC ACID. 337 calcined magnesia, provided it is used at the right time. With regard to the possibility of using the stomach-pump, and its efficiency in sulphoxysm, we can form no reliable opinion, for the want of reported cases on which to base it. We must bear in mind, however, the possibility that the walls of the stomach and oesophagus, which have been softened by the action of the acid, might be artificially perforated by the tube. The further treatment of a case of poisoning must be purely symptomatic. CHAPTER II. POISONING BY HYDROCHLORIC ACID (SPIRIT OF SALT, MARINE ACID, MURIATIC ACID). Anhydrous hydrochloric acid is at ordinary atmospheric pressures a gas, Avhich when exposed to the air forms a white cloud by combining with the aqueous vapor existing in the atmosphere. The preparations of hydrochloric acid used in chemistry, medicine, and the arts, are aqueous solutions of the acid of varying degrees of concentration and purity; they also develop fumes of hydrochloric acid when exposed to the air. These are in the highest degree poisonous to the respiratory organs of animals, and are also very inimical to plants, the life of which it destroys after twenty-four hours' action even at a dilu- tion of 1: 20000 (Christison and Turner'). In other respects the action of hydrochloric acid as a poison is entirely analogous to that of the other mineral acids. Its affinity for water is said to be somewhat weaker than that of sulphuric acid, and the intensity of its corrosive action is also said to be somewhat less marked; but Ave possess very few experimental and clinical data for a comparison of the action of the two acids. Everything that has been stated about the nature of the 1 Christison, loc. cit. VOL. XVII.—22 338 BOEHM.—POISONS. action of sulphuric acid will apply, with a few modifications, to that of hydrochloric acid. Immediately after the poisoning a few observers (Guerard) have seen hydrochloric acid fumes in the expired breath of the subjects, but at a later period these are no longer to be seen. The urine of men and animals poisoned with hydrochloric acid has been found to be rich in chlorides. The few experiments on animals, which were made some time ago by Sproegel, Courton, Yiborg, and Orfila, have afforded scarcely any noticeable results. These experiments Avere performed on dogs and horses, and in some of them the poison was injected into a vein. Recently no toxicological experiments have been made with the acid. Cases of poisoning by hydrochloric acid are rare. Up to the present time only about fourteen cases are to be found recorded in all the literature of toxicology.1 In an etiological connection the easy accessibility of hydrochloric acid, which is much used in the ordinary affairs of life, is of importance. In the majority of the cases known, the poison was taken with suicidal intent; the others are cases of accidental poisoning. Hydrochloric acid fumes can of course also cause poisoning, when they penetrate in any considerable quantities into the respi- ratory organs of human beings. This is not unfrequently the case in factories. The poisonous fumes do not produce general symptoms so much as local affections of the mucous membranes Avith which they may come directly in contact. According to Eulenberg,2 the use of chloride of sulphur in the preparation of vulcanized rubber affords a favorable opportunity for the devel- opment of hydrochloric acid fumes (together with those of sul- phurous acid), since the chloride of sulphur decomposes rapidly Avhen in contact with water or atmospheric air. In the manufacture of bricks, pottery, and glass also, as well as in the making of artificial fertilizers and the like, hydro- chloric acid vapors are frequently given off (Eulenberg). With regard to the quantity of hydrochloric acid required for 1 See Taylor, loo. cit., who also reports in exbenso the cases mentioned by Husemann. Recently cases have been published by Koeppen, Budd, Johnson, Nager, and Paul. 2 Loc. cit. p. 531. MINERAL ACIDS.—HYDROCHLORIC ACID. 339 the production of dangerous or fatal poisoning, the clinical data at our command are too few to allow a general conclusion to be drawn. From the observations recorded, it appears that half an ounce of the concentrated acid can cause death. The following table contains the data having a bearing on this point, which are derived from the cases that have been observed up to the present time. Observer. Quantity of the Poison taken. Result of the Poisoning. Stevenson. 1 wineglassful. Recovery in 8 days. Coll as. 1 ii- Death after a few hours. Budd. Si. Death after 18 hours. Procter. §ss. Recovery in 19 days. Allen. lii. Recovery in about 14 days. GuSrard. §"• Death in 8 hours. Orfila. §iss. Death after a few davs. Johnson. 1 teaspoonful. Death in 16 hours. In the other cases the quantity of the poison taken and the result cannot be accurately ascertained. The symptoms of hydrochloric poisoning agree with those of sulphoxysm in all essential points. The local action on the oral and pharyngeal cavities is some- what less intense in poisoning by muriatic acid, and, according to Paul,1 the results might be mistaken for diphtheria. In some of the cases observed, the pains in the stomach and epigastric region were slight, but they were very severe in the throat (Procter, Johnson). The affections caused by the fumes consist partly in inflam- mation of the conjunctiva, partly in bronchial and laryngeal irri- tation, which have nothing distinctive in themselves. The post- mortem appearances in poisoning by hydrochloric acid present no noteworthy differences from those of poisoning by other min- eral acids. The treatment must be regulated according to the same fundamental principles laid down for sulphuric acid poi- soning. 1 Bullet, gener. de Therap. Oct. 1871. 340 BOEHM.—POISONS. CHAPTER III. POISONING BY NITRIC ACID (ACIDUM NITRICUM, AQUA FORTIS) AND HYPONITRIC ACID (NITROUS ACID).1 Of the various preparations of nitric acid, only three are important from a toxicological standpoint, namely: 1. The officinal pure nitric acid, containing about 28 per cent, of anhy- drous acid, colorless, and, at ordinary temperatures, forming no fumes in the air. 2. The crude nitric acid (aqua fortis), which fumes slightly, and, owing to the presence of various other sub- stances, has a yellow color ; and, 3. The fuming nitric acid, which is essentially a mixture of nitric and hyponitric acids, has an orange-yellow color, and gives off in the air dense, yellowish-red fumes of hyponitric acid.2 The only difference in the toxic action of the three is that, in the case of the two last, the pres- ence of the gaseous hyponitric acid frequently causes compli- cations. Moreover, this gas can by itself produce poisoning. On the whole, nitric acid poisoning also presents so few noticeable differences from sulphuric acid poisoning, that we have scarcely anything to add here, concerning the nature and the symptomatology of the poisoning, to what was said about sulphuric acid. Among the experimental researches we may mention those of Viborg3 and of Blake.4 The former experimented on horses affected with glanders; they recovered after the injection of a drachm of fuming acid into the jugular vein. Blake, after injection of dilute nitric acid into the veins of animals, observed cramps, stoppage of respira- tion, and rapid lowering of the blood-pressure, accompanied after a few minutes by attempts at vomiting. 1 Hyponitric acid and nitric acid are not identical, as appears to be here implied In the new system in chemistry there is no such thing as hyponitric acid, it being nitrogen tetroxide (N20<); nitrous acid is HN02, the corresponding oxide being NjOj ; (nitrogen trioxide).—Translator's Note. 2 See note by translator, above. 3 Nordisch. Archiv. fiir Heilkunde, etc. 1802. * Edin. Med. Journ. 1839. MINERAL ACIDS.—NITRIC ACID. 341 When nitric acid is brought in contact with animal tissues, the well-known yellow coloration appears which we are accus- tomed to ascribe to the formation of xanthoproteic acid. This circumstance is sometimes, though not always, in itself sufficient for the differential diagnosis between sulphuric and nitric acid poisoning. The intensity of the action is naturally proportional to the strength of the acid ; when this is in a concentrated state, the phenomena it produces are scarcely less violent than those caused by sulphuric acid. Wunderlich1 saw one case of nitric acid poisoning take a pe- culiar dysenteric form, while at the same time the symptoms of acute morbus Brightii were present. A point of especial interest in this case was the complete absence of pathologico-anatomical changes in the small intestine, while the large intestine pre- sented the most intense dysenteric lesions. In discussing this state of affairs, Wunderlich refers to Rokitansky' s theory, that dysenteric processes are connected with an acid state of the blood. In other respects the course of the poisoning, the sequelae, and the pathologico-anatomical lesions, present the greatest pos- sible similarity with those of acute sulphoxysm. Though more frequent than poisoning by hydrochloric acid, cases of poisoning by nitric acid, on the whole, occur rarely. In the monograph of Tartra on nitric acid poisoning, which was quoted by Husemann (loc. cit.), but which we unfortunately Avere unable to gain access to, 56 cases are reported, which were all that were recorded during a period of 400 years. In the more recent literature only 20 or 30 cases are mentioned.2 Opportunities for poisoning with nitric acid are plenteously afforded in ordinary life, since this acid also finds manifold applications in the trades and manufactures. Of the cases observed up to the present time, the larger pro- portion are cases of suicide ; one was a case of murder (reported by Cazaulvieilh).3 The rest belong in the catalogue of accidents. 1 Ueber einige Wirkungen concentrirter Salpetersaure auf den menschlichen Organ- ismus. Academ. Programm. 1856. 2 Cf. also Taylor, loc. cit. 3 Annal. d'Hygiene publ. 1836. Murder of a new-born child by its mother. We may 342 BOEHM. —POISONS. On account of the small number of the available observations, the fatal dose cannot be determined with any more certainty than in the case of hydrochloric acid. The treatment is the same as for sulphuric acid poisoning. Poisoning by nitrous acid may be combined with the ordinary poisoning by nitric acid (when considerable quantities of fuming nitric acid are used), and it then modifies to some extent the clinical picture of the latter; or it may occur independently in consequence of the inhalation of larger or smaller quantities of the poisonous gas, which is developed under many different conditions from nitric acid and other chemicals in chemical laboratories, manufactories, telegraph offices, and the like (cf. Eulenberg on this point, loc. cit.). Usually it is the breaking of large vessels filled with fuming nitric acid which furnishes the opportunity for the escape of the gas. It has recently been asserted that the gas frequently accumulates in factory-rooms, and especially in anilin and nitro-benzin factories. To ascertain the action of this gas, Nysten (loc. cit.) made some experiments, which have recently been extended by Eulenberg (loc. cit.). Nevertheless, we are still considerably in the dark as regards the essence of the poisoning, and are unable as yet to determine positively how much of its action is to be ascribed to local influ- ence of the gas, and how much to its remote action. Special stress has been laid upon the black color of the blood, in which, as Eulenberg thinks, nitrogen compounds have formed. The local effects of the gas, which is exceedingly irritating to the air-passages, are very prominent in all cases. They consist in a severe burning sensation in the mucous membrane of the nose, a strangling, suffocating feeling in the windpipe, severe cough (sometimes with bloody expectoration at the very begin- ning), oppression of the chest, dyspnoea, and the other symp- toms of suffocation. Undoubtedly death by suffocation may be provoked imme- diately and solely by the local action of the gas upon the air- passages and the lungs, if it is inhaled in sufficient quantities. class with it also the case in which the poisoning was effected by pouring the acid into the external ear {Taylor, loc. cit. II. p. 59). MINERAL ACIDS.—HYDROFLUORIC ACID. 343 In some cases the violence of the symptoms abated somewhat after a time, but in the course of a few days deep-seated changes in the organs of respiration (pneumonia? bronchitis) gradually developed, and finally resulted also in death. The question whether the alteration of the blood produced by the gas can also produce death by asphyxia, must be left open until further investigations warrant more certain conclusions. The occurrence of general symptoms is, however, positively established; disorders of the organs of digestion (vomiting), as well as of the nervous system, have been observed. Still, it must not be forgotten that probably, as a rule, a certain amount of the gas is swallowed, and reaches the stomach, where it can also produce local symptoms. Prolonged exposure to the action of small quantities of the gas gives rise to chronic forms of laryngitis and bronchitis, and sometimes also to conjunctivitis. At the post-mortem examinations, as a rule, only a more or less marked alteration in the organs of respiration (hyperaemia, swelling, ecchymosis, oedema of the lungs), and the above-men- tioned dark color of the blood, can be positively demonstrated. The treatment of this form of poisoning must be limited to purely symptomatic procedures, after the cause has been re- moved. CHAPTER IV. POISONING BY HYDROFLUORIC ACID. Hydrofluoric acid (HF1) is a colorless liquid which gives off corrosive vapors at ordinary temperatures. In consequence of its great affinity for silica, it attacks glass readily and even dis- solves it. It is the strongest of all the corroding agents now known to us. Although the corrosively poisonous action of its fumes and its aqueous solutions have long been known (the Belgian chemist Louyet is said to have died from inhaling its fumes),1 and the Husemann, Toxikologie. p. 792. 344 BOEHM. —POIS ONS. substance has, moreover, been somewhat extensively used for etching glass, yet hydrofluoric acid did not assume practical importance in a toxicological point of view until the year 1873, when the first case of fatal poisoning by it was observed. On the external skin the acid produces suppurating ulcers, which heal slowly ; its action is attended by intensely severe pain. In the case just mentioned, which Avas reported by King,1 a toper, forty-six years of age, swallowed half an ounce of the acid (concentration not mentioned), and died thirty-five hours after taking the poison, the symptoms being violent vomiting speedily followed by collapse. It was especially noted that the motion of the heart ceased before the respiration. At the autopsy, in addition to other points, an acid reaction of the blood, a separation of the epithelium in the cavity of the mouth and the oesophagus, and a dark red discoloration of the mucous lining of the stomach, were noticed. The contents of the stomach were thick and black. CHAPTER V. POISONING BY SULPHUROUS ACID (ACIDUM SULPHUROSUM). Sulphurous acid (S02)a belongs among the strongly irritating gases. It has a pungent, suffocating odor, an acid reaction, is readily soluble in water, but in aqueous solution changes immedi- ately into sulphuric3 acid. Since it is developed in large quan- tities in a large number of technical processes during which it is partially diffused in the air of the factory and workrooms, it might be supposed that it must frequently give rise to serious cases of poisoning. Practical experience proves, however, that 1 Reported by Th. Husemann, in Virchow and Hirsch's Jahresber. 1873. I. 358. 2 According to the new nomenclature SOi is sulphur dioxide or sulphurous oxide, and this oxide, combined with water (H,S03), constitutes sulphurous acid. The author throughout this chapter applies the term sulphurous acid to the sulphur dioxide.— Translator's Note. 3 See Eulenberg on this point: Schadliche und giftige Gase; and Hirt, Krank- heiten der Arbeiter. I. MINERAL ACIDS.—SULPHUROUS ACID. 345 the reverse is true, and we must unquestionably class sulphurous acid gas among the toxicologically unimportant substances. Recently Eulenberg (loc. cit.) and L. Hirt (loc. cit.) have instituted investigations to determine the nature of the action of sulphurous acid. The results obtained by the latter author especially are of great theoretical interest. He found that the gas, when inspired in different degrees of concentration by ani- mals, produced partly local and partly remote effects, the latter being evidently consecutive to the absorption of the poison into the blood. The pause in respiration during expiration—which invariably followed inhalation of the poisonous gas through the mouth or nose, persisted for from twenty-five to thirty hours, and sometimes recurred again and again—must be regarded as a reflex phenomenon caused by the irritation of the sensory nerves of the nasal mucous membrane. It did not appear when the sulphurous acid was conducted through a canula below the larynx directly into the trachea. The poison, moreover, pro- duced labored, dyspnoeic breathing, diminution in the frequency of the respiration, and finally stoppage of respiration by paraly- sis of the respiratory centre. Animals in Avhich the vagi had been divided bore more sulphurous acid than uninjured ani- mals. Hirt observed inflammation of the lungs after the inhalation of concentrated fumes. The action of the poison extends also to the innervation of the vessels and the heart. The vaso-motor centre is at first excited, and afterwards paralyzed (decrease of arterial blood-pressure) by small doses ; large doses cause paraly- sis at once. The effect on the heart, in Hirt's opinion, is due to the direct injurious action of the poison on the cardiac muscle. In the animals poisoned with sulphurous acid, the blood showed no notable alteration. It is evident from these statements that it is still doubtful how large a proportion of the entire effect produced by sulphur- ous acid on the respiration and circulation is attributable to its local action, and how much to a remote action. For the present Ave must rest contented with our ability to demonstrate the existence of both kinds of action. Very few cases of acute and fatal poisoning by sulphurous 346 BOEHM.—POISONS. fumes are on record, and even they belong to earlier times.' Death ensues with symptoms of severe asphyxia. The disorders observed among workmen who are exposed to an atmosphere saturated with sulphurous acid fumes, are, as a rule, trifling—if the proportion of the poisonous gas in the air is within the ordinary limits—namely, from 2 to 4 per cent. The difficulties consist chiefly in anomalies of digestion.2 Hirt denies absolutely any special tendency to serious affections of the lungs among such persons. When the atmosphere contains from 5 to 7 per cent, of the gas, a prolonged stay in it usually produces severe bronchial irritation—long-continued fits of coughing, and also conjunctivitis—phenomena which disappear only after re- moval from the poisoned atmosphere. B. Vegetable Acids. CHAPTER VI. POISONING BY ACETIC ACID (ACIDUM ACETICUM). In a diluted form (vinegar), acetic acid, as is well known, finds very extensive use as a condiment with various kinds of vege- table and animal food. Used in proper quantities, vinegar is rather beneficial than hurtful to health: an excessive use of the acid, however, cannot be borne long without injury. Concentrated acetic acid, and especially the anhydrous or so-called glacial acid (acidum aceticum glaciale) are corrosive poisons, the action of which is but little inferior to that of the weaker mineral acids. Acetic acid (C2H402) is volatile, and its fumes have a peculiar, pungent odor, which in a slight degree is possessed also by vinegar. It is miscible in all proportions with water, and with the bases forms different series of salts. When brought in contact with the constituents of the animal body, it 1 Cf. Husemanrts Toxikologie on this point. 2 The inhalation of sulphurous acid for a short time, and in small quantities, is said to cause an increased appetite. Hirt tested this action upon himself. VEGETABLE ACIDS.—ACETIC ACID. 347 asserts its chemical affinities by combining with the available water and with the free bases, or those which are in combination with carbonic acid ; it also unites with the albuminoid substances. Even before it is absorbed by the mucous membranes, a portion of the free acid is fixed by the processes just mentioned, while the remainder, which is taken up by the blood, undergoes similar changes with the constituents of that fluid. The local corrosive action of the acid is incontestably also to be referred to its affinity for water, bases, and albuminous substances. It has not yet been ascertained whether appreciable quantities of the acid may be introduced into the blood by breathing the fumes. These fumes, however, in proportion to their concentration, act as a more or less intense irritant to the mucous coats of the air-passages. It has been demonstrated by the researches of Krause and Bobrik,1 that acetic acid can also make its way into the blood through the uninjured epidermis. Bobrik observed in himself a thread-like and noticeably retarded pulse, and a decrease ol f° C. (1.35° Fahr.) in the temperature of the body after a foot- bath consisting of three bottles of strong vinegar. With regard to the behavior of acetic acid in the blood and tissues, and the form in which it is eliminated, there are as yet no accurate researches on record. Still, we may assume that the blood ol living animals cannot contain free acetic acid for a long time any more than it can contain other free acids. The blood of animals poisoned by acetic acid has never been found acid. It is, more- over, highly probable that the acetates, like other salts formed by the organic acids, are changed into carbonates in the organism. As early as 1827, Woehler * proved that free organic acids (oxalic, tartaric) are excreted in the urine of the dog ; the crystalline lime salts formed with these acids were deposited on the walls of the urine vessels. When, however, alkaline salts formed with vegetable acids were administered to the animal, carbonic acid appeared in the urine instead of the vegetable acid. With regard to the point where the conversion of the vegetable acid into carbonic acid took place, Woehler only showed that the stomach is not instrumental in effecting the change. The vomit of the animals, even several hours after the administration of the vegetable salts, did not have any alkaline reaction. 1 Acid a et vegetabilia et mineralia qualem vim atque affectum habeant, etc. Diss. Konigsberg. 1863. 2 Hufeland's Journal d. prakt. Heilkunde. 1827. 64. Vol. I. St. p. 86. 348 BOEHM.—POISONS. The action of acetic acid on the animal organism agrees entirely in its essential points with that of other strong acids. Its behavior towards the various chemical constituents of the body has been determined accurately by the researches of Mit- scherlich,1 Lehmann,2 and others. Since the physiologico-chemi- cal results have no special bearings on toxicology, we think we may pass them over here. Among other things, it was found that the red blood-corpuscles were dissolved by acetic acid, and attempts have been made to explain certain effects, e. g., decrease in the temperature of the body and frequency of the pulse, (Heine3) by this fact, though the proof is still wanting that the solution which is observed under the microscope also occurs in the living blood. Munk and Leyden4 assert that tartaric and oxalic acids dissolve the red blood- corpuscles in the living blood. They do not mention acetic acid in this connection. Goltz and Bobrik have shown that acetic acid (as also other vegetable acids, tartaric, citric, etc.) exerts a specific influence on the heart of frogs and warm-blooded animals independently of any action on the nervous system. In the former, after the appli- cation of the acid in various ways, the number and energy of the heart-beats were diminished until they stopped completely. In rabbits also a stoppage of the heart for several minutes could be effected by injecting the acid into a vein. Bobrik demonstrated on himself the action which the acid exerts in diminishing the temperature and retarding and weakening the pulse. It is a specially interesting point, that, according to Bobrik's researches, dilute mineral acids have just the contrary effect, inasmuch as the frequency and strength of the pulse is never lessened by them, but is, on the contrary, regularly increased. While, in accordance with Bobrik's experience, we must admit that vegetable acids, and especially acetic acid, have a spe- cific action upon the heart, some more recent observations and researches made by Heine (loc. cit.) on men and animals make 1 De acidi acet., oxalic, etc. etc. affectu. Berolin. 1845. 9 Med. Centralblatt. 3 Virchow's Archiv. XLI. 1868. 4 Berlin, klin. Wochenschrift. 1864. Nos. 49 and 50. VEGETABLE ACIDS.—ACETIC ACID. 349 it probable that the functions of the nervous system are also affected by large doses of acetic acid. Heine observed in animals periodical tetanic spasms, in men general tremor of the muscles, shivering and exceedingly rapid collapse. The last-mentioned symptom might, it is true, have been due to anomalies in the circulation, to great feebleness in the action of the heart. The rapid death of animals, into whose blood considerable quantities of concentrated acid have been injected, is evidently due to the alterations in the blood caused by the powerful chem- ical agent. The local action of acetic acid presents but little that is char- acteristic. Its intensity is in direct ratio to the concentration of the acid. While diluted acid produces only severe burning sensations and temporary hyperaemia, stronger solutions cause vesication and, when applied for a long time, ulcers and eschars. Selinsky' asserts that he produced artificial croup membranes by injecting acetic acid into the air-passages. On the mucous coats of the intestinal canal it effects exactly the same alterations as do the weaker mineral acids. The entire number of cases of acute acetic acid poisoning, hitherto recorded in medical literature, only amounts to six. Of these two resulted fatally (Heine and Hergott) from the injection of liquor Villati into suppurating wounds. Heine has proved experimentally that the acetic acid is in fact the toxic agent in the liquor Villati. This solution consists of half an ounce each of cupric and zincic sulphates, seven drachms of solution of subacetate of lead, and six and a half ounces of acetic acid. A dose of acetic acid corresponding to the quantity of the acid contained in the liquor Villati killed a dog in two minutes, while a corre- sponding amount of liquor Villati, from which the acetic acid only was omitted, proved harmless. The cases of Orfila,2 Barruel,1 and Birkett4 were attempts at suicide, and that of Mellon" resulted from an accidental ex- change of the acid with a medicine. Of these four cases tAvo terminated fatally. 1 Petersb. med. Zeitschrift. VI. 1864. 3 Husemann, Toxicologic 2 Toxikologie. I. 4 Lancet, 1867 6 Frank's Magaz. 350 BOEHM.—POISONS. All the handbooks also mention a chronic form of acetic acid poisoning, which is said to occur sometimes as the result of the excessive use of vinegar by hysterical persons, or by women Avho take it for the sake of obtaining a pale complexion. This form is said even to lead to phthisis. We have been unable, how- ever, to discover any detailed observations of such chronic poisoning. Finally, a prolonged stay in the rooms of vinegar distilleries, or vinegar factories, is said also to exert an injurious influence on the health (to predispose to phthisis). The workmen occupied there are said to suffer not only from the pungent acetous fumes, but also from the lack of oxygen in the atmosphere ; in the pro- duction of acetic acid the oxygen used is taken exclusively from the surrounding air. On this point also reliable individual observations are lacking. It is impossible to determine what constitutes a poisonous or fatal dose on account of the small number of recorded cases, which are, moreover, very incomplete in regard to the quantities of the acid taken, the degree of concentration, etc. That diluted acetic acid can be taken in large quantities without injury is proved by daily experience. The symptoms after poisoning by acetic acid per os consist in severe burning pains, which supervene immediately after tak- ing the acid, and extend to the stomach and abdomen, dyspha- gia, bloody vomit, diarrhoea, to which, in the more serious cases, the symptoms of a more or less severe collapse are added. Birkett's case (loc. cit.) was notable from the fact that a good deal of the acid flowed into the air-passages, and provoked vio- lent symptoms of suffocation, which, however, were fortunately relieved by timely tracheotomy. In the case described by Heine (loc. cit.), in which liquor Villati was injected into a resection Avound on the ankle, which was healing badly, and was becom- ing covered with croupous membranes, the injection was imme- diately followed by bleeding from the Avound, and violent pains in it. These were soon followed by death-like pallor, trembling of the entire body, with great chilliness, and a very rapid and \veak pulse. The patient died in a feAv hours from rapidly increasing collapse. In Hergott's case, nausea and vomiting VEGETABLE ACIDS.—OXALIC ACID. 351 immediately followed the injection, and death also ensued in a very short time. In chronic acetic acid poisoning, progressive deterioration of the nutrition and general emaciation are said to occur in conse- quence of the disorders of digestion. Respecting the post-mortem appearances and the treatment of acetic acid poisoning, we have nothing to add to what has already been said concerning poisoning by the other acids. The odor of acetic acid can, of course, serve as a foothold in the diag- nosis of doubtful cases. CHAPTER VII. POISONING BY TARTARIC ACID (ACIDUM TARTARICUM) AND CITRIC ACID (ACIDUM CITRICUM). The effects of both of these acids, which in the chemically pure state are crystalline, and readily soluble in water, corre- spond in all respects with those of acetic acid. Hence, an extended notice of them is superfluous. Several cases of poisoning, some of them fatal, have resulted from tartaric acid, which is used very extensively in every-day life as a household medicine and in technical applications. CHAPTER VIII. POISONING BY OXALIC ACID. Oxalic acid (H,C204) indisputably occupies the first rank among organic acids in a toxicological point of vieAv, on account both of the intensity of its action and of the number of cases of poisoning caused by it. Besides the free oxalic acid, which is crystalline in form, and readily soluble in water, the potassium oxalate, or salt of sorrel of commerce, is the only preparation of oxalic acid which is of 352 BOEHM. —POISONS. importance as a poison. Its action is essentially the same as that of the free acid. This acid possesses in a high degree the caustic and corrosive action on the tissues of the animal organism which is common to all acids, but, in addition to it, produces also very decided effects on the nervous system, which modify considerably the general clinical picture of the poisoning. As regards its corrosive action, we may content ourselves with referring to the detailed description given of this action in the case of sulphuric acid. The corrosive action of sulphuric acid is, however, somewhat more intense than that of oxalic acid. The action of oxalic acid on the nervous system has been explained in various ways. Onsum * is of the opinion that oxalic acid, after entering the blood, combines with the lime salts in that fluid, to form the insoluble oxalate of lime, which causes death by clogging the capillary vessels of the lungs. This view is warmly combated by Cyon,2 who has tried to prove that oxalic acid is a heart-poison. Still Cyon's experiments are too few in number to warrant a positive conclusion regarding the nature of the remote action of oxalic acid, though Onsum's view has hardly any followers at present. Buchheim3 assumes, in addition to the corrosive action of oxalic acid, a general action on the heart and the nervous sys- tem, which also belongs to its soluble compounds. He calls attention also to the high degree of diffusibility which is charac- teristic of oxalic acid and its soluble compounds ; in consequence of this property the oxalic acid compounds can be given in small doses for a long time without injurious results, since they are eliminated in the urine almost immediately after being intro- duced into the system. 1 On the toxic action of baryta and oxalic acid compounds. Virchow's Archiv. Vol. 28. p. 233 (1863). 2 On the toxic action of baryta and oxalic acid compounds. Arch, f. Anat. u Physiol., by DuBois and Reichert. 1866. p. 196. 3 Arzneimittellehre. II. Ed. p. 189. Ueber den Uebergang einiger organischen Sauren in den Ham. Arch. f. physiol. Heilkunde. 1857. Pietrowski, Dissertation. Dorpat. VEGETABLE ACIDS.—OXALIC ACID. 353 We are indebted to Christison and Coindet' for very thorough experimental researches on the action of oxalic acid; their results, however, differ in no respect from those just indicated. In Germany cases of poisoning by oxalic acid occur rather infrequently, but in England they constitute no small proportion of the cases of poisoning observed annually. Out of 527 cases of poisoning occurring in the years 1837-1838, in England, 19 were caused by oxalic acid.2 As a rule, it seems to have been used with suicidal intent. Several cases of accidental poisoning have occurred in consequence of the oxalic acid being mistaken for magnesium sulphate, tartaric acid (Seidlitz powder), cream of tartar, and the like. Attempts at murder with oxalic acid have also been made in England, though they were thwarted by the intensely acid taste of the poison, which it is difficult to mask. Thudichum3 has attempted to settle by experiment the question whether it is possible to poison a person with oxalic acid without his knowledge. He found that even doses of ten grains, which is not really a poisonous dose, although greatly diluted and disguised with various substances (oatmeal gruel, etc.), produced an unendurable flavor that manifested itself immediately, and left behind for some time a feeling of the teeth being " set on edge." From the literature of the last thirty years, which we have had at our disposal, we have collected 22 cases of oxalic acid poisoning. Of these 19 occurred in England, and 3 in France and Germany. Twelve terminated in death, and ten in recovery. In eight cases suicide had been attempted. The fatal dose of oxalic acid cannot be certainly fixed upon. Death has been known to follow the administration of two drachms, but recovery has resulted after a half ounce or more was taken. It makes quite a* difference whether the poison is taken in the solid form or in a more or less concentrated solu- tion. We will only discuss here those symptoms of oxalic acid poisoning which relate to the so-called constitutional action of this substance, since the local phenomena are the same as those 1 Edinb. Med. Journ. Vol. XIX. 1823. ! Husemann, loc. cit. p. 353. 3 Med. Times and Gazette. April, 1860. VOL. XVII.—23 354 BOEHM.—POISONS. caused by sulphuric acid. Apart from a more or less marked shortness of breath, which, though described by certain authors as characteristic of this form of poisoning, may really be due to local disturbances, and are known to occur in poisoning by other acids, the symptoms which indicate an affection of the nervous system are principally located in the sensitive and motor sphere of the same. Formication, both on the trunk and on the extremities, numb- ness and anaesthesia of the finger-tips, dragging pains in the back and lower extremities, tonic and clonic spasms, have been quite often observed, and death frequently ensued with tetanic parox- ysms. Affections of the kidneys also, similar to those which occur in the case of poisoning by vegetable substances—namely, pains in the region of the kidneys and loins, extending toward the extremities, with painful urination—were observed by Chris- tison and Webb,1 but at the same time it was particularly notice- able that the affection of the stomach was slight and evanescent or entirely absent. Perhaps these phenomena are connected with the rapid elimination of the oxalic acid compounds demon- strated by Buchheim. The course is sometimes extremely violent, causing death in a few minutes, and sometimes more retarded and chronic. Recovery may be preceded by the same sequelae as are met with in sulphoxysm and other analogous venenations. On reading the accounts of many cases of oxalic acid poison- ing, the general impression left is that there is very little constancy in the phenomena and symptoms, and that both the local and the constitutional manifestations appear in the most manifold combinations, the exact description of which would be synonymous with a complete report of all the cases observed. We are unable to name a single really pathognomonic symptom of oxalic acid poisoning. The pathologico-anatomical lesions also present nothing that is characteristic. When dilute solutions of the acid have been used as the poison, anatomical changes in the corpse may be altogether wanting. 1 Husemann, loc. cit. ALKALIES.—AMMONIA AND SAL AMMONIAC. 355 In the treatment of oxalic acid poisoning the preparations of lime constitute the best antidote, because of the insolubility of the oxalate of lime, but magnesia may also be used, and in case of necessity chalk-water, egg-shells, and the like may prove useful. Recently Husemann1 has recommended sugar-lime as a suitable antidote. He has obtained experimentally with this substance very favorable results in carbolic acid poisoning. He remarks especially that the quantity of lime required to neutral- ize the acid can hardly be administered in the form of lime-water, and that the use of the carbonate of lime is inconvenient on account of the voluminous disengagement of carbonic acid. The alkalies are of course counterindicated, since it is well known that their combinations with oxalic acid are not only readily soluble in water, but are also themselves extremely poisonous substances. THIRD DIVISION. Poisoning by Alkalies, Earths, and their Salts. CHAPTER I. POISONING BY AMMONIA AND SAL AMMONIAC. Aqueous and gaseous caustic ammonia (water of ammonia, ammonium carbonate and chloride (sal ammoniac) are the few ammonia compounds which are of importance from a toxico- logical standpoint. The ammonia fumes, which escape not only from aqueous solutions of the free base, but also from those of the carbonate, have a characteristic, pungent, unpleasant odor. They are 1 Deutsche Klinik. 1870, 1871. Unfortunately this antidote up to this date has not been adopted into the pharmacopoeias, a fact which it is well to bear in mind in pre- scribing for an urgent case of poisoning. 356 BOEHM. —POISONS. colorless and not combustible in the air. The other salts have no specially characteristic external properties. The absorption of the ammonia salts into the animal organ- ism takes place in the case of the volatile compounds both through the organs of respiration and also through all the mem- branes and surfaces of the body through which processes of diffusion can occur. The non-volatile salts can, of course, only be absorbed through the latter. The elimination of the ammonia compounds and their beha- vior while in the body have frequently been the subject of elaborate investigations. Various authors state that after the administration both of free ammonia and of the salts of this base, they have frequently detected the gaseous ammonia in the expired air, over and above the small quantities which are said to be normally present in the expired breath of animals and men. The statement has been positively refuted by some recent researches which Avere made on rabbits and cats by Schiffer' and also by Lange2 under our OAvn supervision. Elimination through the lungs does not occur even when the elimination in the urine is prevented by ligation or removal of both kidneys. It can hardly be assumed that the human organism would act differently in this respect, though the direct proof can only be furnished for the above-named species of animals. The elimination of ammonia in the perspiration has not yet been demonstrated experimentally, although Castan3 has re- cently declared that he smelt the gas in the cutaneous excretion of a person poisoned by ammonia. Lohrer4 made, under Buch- heim's direction, some experiments on himself and on dogs, to determine the passage of the ammonia compounds into the urine, which led him to the conclusion that all the different salts of this base leave the organism in the urine after varying periods of time. However, these results still require confirmation, inas- 1 Berlin klin. Wochenschr. 1872. No. 42. 2 Inau.-Diss. Dorpat. 1874. und Archiv f. experim. Path. u. Pharmak. II. 1874. 3 Montpellier med. 1870. cit. in Jahresber. of Virch. and Hirsch. vid. Hus. 4 Inaug.-Dissert. Dorpat. 1862. ALKALIES.—AMMONIA AND SAL AMMONIAC. 357 much as there is reason to doubt the accuracy of the Neubaur- Schloesing method for determining the presence of ammonia which was used by Lohrer.1 Lange (loc. cit.) has sought in vain for free ammonia in the blood of animals, into which large quan- tities of ammonia compounds had been injected during life by the jugular vein. The ammonia reaction only showed at a temperature at which the decomposition of the albuminoid con- stituents of the blood might have produced fresh ammonia. According to the recent researches of Knieriem,2 the major part of the ammonia taken into the system is transformed into urea, in which form it appears in the urine. The general phenomena occurring after the absorption of ammonia compounds are common to all the combinations of this base, but some of them are also characterized by an exception- ally severe local action. In the case of the gaseous combinations this local action affects the organs of respiration, while, where an aqueous solution of caustic ammonia is swalloAved, the mucous coats of the digestive tract are attacked. The caustic action of the latter manifests itself also when it is applied to the external skin. In their nature the local actions of the gaseous preparations and of the aqueous solutions of ammonia are closely related ; at least it is difficult to perceive why gaseous ammonia, as well as the solution, obeying its affinity for water, should not extract from the tissues that substance which is their most important constituent. The local effects of ammonia on organs containing nerves are, under all circumstances, coupled with the phenomena of intense irritation of the sensitive nerves, which manifests itself not only by violent pains, but also (in the air-passages) by energetic reflex action. Thus ammonia fumes, when at all concentrated, pro- duce at once, by reflex action, convulsive expiratory movements, fits of coughing, such as occur in animals after central irritation of the nervus laryngeus superior, and spasmodic closure of the glottis. Whether or not these phenomena of intense irritation 1 See Lange, loc cit. 8 Zeitschr. f. Biologie. 1875. 358 BOEHM.—POISONS. are also connected with the chemical action of the ammonia (ab- straction of water) cannot for the present be decided. In other respects the local phenomena are similar in charac- ter to the effects produced by other inflammatory irritants. The assertion that ammonia, when applied either in fluid or gaseous form to the mucous membrane of the larynx and trachea, pro- duces croupous pseudo-membranes, which are regarded by Reitz ' and Oertel2 as the product of a genuine croupous inflammation, has recently been subjected to a thorough test by Heinrich Mayer.3 He came to the conclusion that the products of the inflammation excited in the air-passages by the poison present at the outside only a macroscopic resemblance to croup membranes, but otherwise lack all the essential characters of that form of exudation. The affection is a simple inflammation. The study of the phenomena which ensue after the absorption of poisonous quantities of ammonium compounds establishes beyond question the fact that all the salts of this base exert the same action—varying only in intensity—on the organs of the nervous system and of the circulation. Lange and the writer have proved experimentally that even ammonium chloride does not, as some authors assume,4 form an exception to this rule ; on the contrary, it is distinguished by an especially energetic action upon the nerves. The most striking phenomena are the disturbances of respiration and of the voluntary movements. The former consists in an enormous increase in the frequency of the respiration, which succeeds a short pause in the breathing that occurs immediately after the administration of the poison ; we ascribe it to a central irritation, by the poison, of the respira- tory tract in the medulla oblongata. This irritation is so intense that it even leads to a marked acceleration of the breathing in animals whose nervi vagi were previously severed. This fact is of practical significance, since it affords a theoretical basis for the employment of injections of ammonia, which have been recommended in the treatment of certain forms of asphyxia. 1 Wiener Sitzungsbericht. Vol. LV. 2. 1867. 2 Deutsches Archiv f. klin. Med. VIII. 1871. 3 Arch. d. Heilkunde. 1873. VI. 512. 4 Buchheim, Arzneimittellehre. II. ed. p. 175. ALKALIES.—AMMONIA AND SAL AMMONIAC. 359 The tetanic convulsions provoked by the ammonium com- pounds proceed from the spinal cord. This is evident from the fact that they occur also in animals in which the cervical marrow has been severed between the atlas and axis, and which are kept alive by artificial respiration. The action which all the ammonium compounds exert on the circulation consists in an enormous increase in the blood-pres- sure. This Avas first observed by Blake,' and has recently been investigated by Lange and the writer (loc. cit.), and also by Funke and De Ahna.* The alterations which the frequency of the pulse undergoes under these conditions are inconstant and unim- portant. Experiments on animals, after division of the cord in the cervical region, showed that the increase of pressure could not be referred to some central influence, emanating from the medulla oblongata. Very large doses diminish the blood-pressure so much that the animal succumbs, and at the same time they deprive the respiratory centres of their excitability and vitality. The phenomena described, so far as they relate to the respi- ration, are most intense, and are developed most rapidly, when they are provoked by the carbonate or by free ammonia ; after the administration of ammonium chloride, on the other hand, the action upon the blood-pressure is most prominent, though the disturbance of the respiration is also sufficiently marked. In both respects ammonium sulphate has the weakest action of all the preparations. L. Hirt3 has recently investigated the alterations which the blood of animals undergoes after the inhalation of large quantities of ammonia fumes. He found that the blood really does assume a dark, broAvnish-red color, but when exposed to the atmospheric air it immediately becomes bright red again. The results of the spectrum analysis are in every respect the same as those given by normal blood. The red blood-corpuscles are only destroyed when ammonia gas is intro- duced in large quantities into the blood. The toxic action of the ammonium compounds consequently 1 Edinb. Med. Journ. 1847. 3 Pfluegefs Archiv. IX. 3 Krankheiten der Arbeiter. I. p. 93, 360 BOEHM. —POISONS. consists essentially in local phenomena of irritation, and in a general action on the nerve-centres and the circulation. The non-volatile ammonium salts only cause disorders in the alimentary canal when they are ingested in large quantities and in a highly concentrated form. Cases of ammoniacal poisoning arise as well from the mani- fold applications of the ammonium compounds, in trades and manufactures, as from accident; in rare cases they are suicidal in nature. Hirt has proved (loc. cit.) that the injurious action of ammonia fumes, which are developed incidentally in many chemical works, has been greatly over-estimated, since tolerably large quantities of it can be inhaled by the workmen without special injury to health. Very violent symptoms of poisoning- are only provoked by prolonged inhalation of concentrated ammonia fumes. Very complete data respecting the development of ammonia fumes are given by Eulenberg (loc. cit.). We will allude here only to the presence of this noxious gas in sewers and privy vaults, because it explains the locally irritating action which the gases produced in such places frequently exert. The degree of con- centration which ammonia fumes can attain in badly appointed privies is often so great, that under certain circumstances they may even cause serious poisoning. Medical literature contains only a few cases of poisoning by gaseous ammonia. In a case reported by Tardieu,1 a physician, while in an epileptic fit, was poisoned with ammonia by a porter; the latter, in the attempt to bring the sufferer to his senses, having held a handkerchief, soaked in ammonia, to his nose, and thrust it into his mouth. The case ended fatally, and Nysten found at the autopsy excessive croupous (?) inflammation of the air-passages. In two other cases of poisoning by ammonia fumes, the vic- tims were druggists, and in both the poisoning was brought about in the same way—namely, by the breaking of large flasks filled with ammonia.2 Quite recently a similar accident occurred 1 Etude medico-legale sur l'empoisonnement, etc. p. 285. 2 Souchard, Ann. d'hyg. publ. 1841. I. p. 219. ALKALIES.—AMMONIA AND SAL AMMONIAC. 361 with an ice-machine, which proved fatal to a workman who was tending it. The careless use of water of ammonia to revive fainting drunken, or asphyxiated persons, also sometimes causes poison- ing. Besides the above-mentioned case of Tardieu's an analogous case, which, however, terminated in recovery, is recorded by Delioux de Savignac,! while a third, in which ammonia was per- sistently held under the nose of an epileptic, terminated in death.2 The cases of poisoning by solutions of ammonia are some- what more numerous. They were mostly the result of accident and of inadvertent medicinal use of the drug. With one excep- tion, in all the cases belonging in this category, which are recorded in medical literature, the ammonia was taken inter- nally. The exception is a case reported by Paget,3 in which a dilute solution of caustic ammonia was injected into a naevus. The patient, a child two years of age, died in convulsions imme- diately after the injection. Regarding the quantity of ammonia or of ammonium salts necessary to produce poisoning and death, nothing positive can be stated; on the one hand, because the observations made on human beings are too few in number, and on the other, because in the individual cases the quantity of the poison used can sel- dom be determined. We Avill not attempt, therefore, to give any figures on this point. In the majority of cases the poison used was caustic ammonia; cases of poisoning by the carbonate and chloride are rare. The following small table of statistics, in which the writer has inserted all the cases that are to be found in the medical literature at his command, contains all the points that can be educed from this available material.4 1 Castan, Montpell. med. 1870. 2 Diction, encyclopaed. des scienc. med. I. Ser. III. 1869. 3 Christison, loc. cit. 233. 4 The cases are collected from Schmidt's Jahrbuch, the handbooks on toxicology of Tardieu, Taylor, and Christison, the Dictionnaire encyclopedique des sciences medi- cales; the sources of some are mentioned above. 362 BOEHM. —POISONS. c Di 5 19 1 1 d E o 8 1 fi s o 1 2 Kesult. Occasion. Form in which the poison was taken. Kecov-ery. Death. Acci-dent. Medical Use. Suicide. Murder. 1. Caustic ammonia. a) inhaled. b) internal. c) subcutaneous. 2. Ammonium car-bonate. 3. Chloride. 3 12 2 1 2 15 1 2 4 14 1 1 1 3 1 1 9 1 i l 5 27 1 4 1 Total.......... 26 9 3 1 18 20 20 6 10 2 38 If it be at all allowable to attempt the production of a general clinical picture from the symptomatic material furnished by the few cases of ammonia poisoning in man hitherto reported, spe- cial stress must be laid on the following principal features. In most cases the phenomena produced by the local action of the poison are much the more prominent, those symptoms which, as we have learned from experiments on animals, depend upon the constitutional action of the ammonia being rarely very markedly developed. Thus ammonia poisoning presents an undeniable similarity to the intoxications provoked by the other corrosive poisons. The amounts necessary to produce the general toxic action in men seem to be pretty large. It may be that the local phenomena excited by caustic ammonia render the absorption of large quantities into the blood impossible. As with all corrosive poisons, so in poisoning by ammonia, the reaction of the organism is immediate, whether the toxic action be produced by the penetration of the fumes of the base into the air-passages or of the aqueous solution into the intestinal canal. Very severe pains in the mouth, pharynx, larynx, and along the trachea usher in the symptoms, and excite the active reflex action. Not infrequently the intensity of this irritation of the sensitive nerves is so great that it causes complete insensibility, which lasts, however, only a short time. When the gas is inhaled, the organism responds by spasmo- dic expiration and temporary closure of the glottis, and thus ALKALIES.—AMMONIA AND SAL AMMONIAC. 363 prevents the admission of more of the irrespirable substance. AYhen the poison is taken in the fluid form, whether it be taken accidentally or intentionally, the intense pain, as a rule, causes it to be spat out immediately. Even the firmest determination to commit suicide is paralyzed by the physical pain, which drives all other considerations out of the mind. The disturbances of respiration are not confined to the cases in which the poison has been inhaled; they are also observed after it has been taken by the mouth more frequently than they are in the case of any of the other poisons. The reason for this is either because the solution, while in the oral cavity, evolves fumes in considerable quantities, which find their way into the neighboring air-passages, or because some of the solution itself gets into these passages. After the cessation of the spasmodic reflex movements, a per- sistent and violent burning pain, which is experienced through- out the whole extent of the air-passages, is the most prominent symptom. It is combined with a more or less frequent and labored respiration, interrupted by violent fits of coughing. In consequence of the increased secretion from the mucous glands, caused by the severe irritation, the trachea and bronchial tubes are soon filled with secretion, which is often mixed Avith blood, and is expelled in large quantities during the paroxysms of coughing. The moist rales produced by it are easily distin- guished by auscultation. The vocal cords, as a rule, cease to perform their work. Either complete aphonia occurs, or speaking aloud, when at all possible, causes severe pain and coughing. All these phenomena increase in intensity during the first few days after the poisoning. In consequence of the increasing aavoH- ing of the mucous membranes, and the gradual development of denser masses of exudation and ulcers, the lumen of the air- passages becomes more and more reduced, and the breathing becomes more labored. The frequency of respiration increases at the same time. A painful feeling of suffocation, accompanied by violent pains in the region of the larynx and under the ster- num, deprives the patient of sleep. Even after slight poisoning by ammonia fumes, a severe catarrh of the air-passages is left, 364 BOEHM. —POISONS. which persists for a long time. The lungs themselves, as it appears, are not, as a rule, involved in the inflammation. In only a very few cases have the vestiges of a pneumonia been found at the autopsy. As might be expected, however, when- ever the above-described phenomena persist for a long time, they may readily prove fatal through the agency of oedema of the lungs. Scarcely less intense are the local symptoms of reaction, when considerable quantities of caustic ammonia are taken into the mouth and stomach. The most violent pains are experienced wherever the poison comes in contact with the mucous mem- brane, which is richly supplied with nerves ; they are especially severe in the pharynx and throughout the length of the oesopha- gus, where they are usually felt immediately after the poison is taken, while the pain in the epigastrium, which is very constantly present, appears later. Great difficulty in swallowing and vio- lent vomiting follow quickly upon the ingestion of the poison. On the organs of the mouth the poison leaves visible traces of its action. The lips swell greatly, as do also the tongue and the soft palate, the last assuming at the same time a bright scar- let hue; small extravasations of blood may also be found upon them. In two cases profuse salivation 1 AAras observed. The mat- ter ejected during the frequent attacks of vomiting contains more or less blood, and much tough mucus. The faeces and urine are sometimes retained at first, but later on abundant discharges occur, Avhich at times are passed involuntarily. In several cases the patients were exhausted by very obstinate, profuse, bloody diarrhoeas. The epigastric pain is scarcely ever Avanting, and the abdomen is very sensitive to pressure. The administration of nourishment is attended Avith great difficulty, on account of the extreme dysphagia. The pulse usually becomes very rapid (140), and is at the same time small and weak. The temperature of the body appears to be reduced, the extremities are cold, and the patients invari- ably complain of feeling cold. In a very few of the cases fever set in at a later stage. Case of Fonssagrives, by Tardieu, loc. cit. ALKALIES.—AMMONIA. 365 In general the patient presents the picture of profound col- lapse : the face is pale, the eyeballs are sunken and surrounded by dark rings, and the visible mucous membranes are livid or cyanotic. The sensorium is, as a rule, unaffected, and the patient is fully conscious of the agony he is suffering. At a later stage somnolence and sopor supervene ; convulsions and other nervous symptoms have been but seldom observed, and then only in cases where camphor had been administered in addition to the ammonia. Wandering neuralgic pains in the muscles, formication, and complete anaesthesia, ringing in the ears and dizziness, are symp- toms of which mention has been made only in a feAv cases, among which the only case of poisoning by sal ammoniac,1 which can be found in the literature, is included. In the case of the two-year- old child already mentioned, the injection of ammonia into a nsevus immediately caused violent general convulsions and death. The case reported by Potain,8 in which a diffused erysipelas accompanied the ammonia poisoning, is also unique. The course and termination of poisoning by ammonia compounds are of course determined by the quantity of the poison used, and the therapeutic means resorted to. On the whole, the course is comparatively slow, the symptoms lasting for several days or even weeks. Death is due either to the disturbances of respira- tion, or to the weakness resulting from the affection of the digestive organs. In mild cases the recovery is rapid and com- plete, and is not followed by any serious sequelae. The pathologico-anatomical lesions of this form of intoxica- tion, like those of many others, present nothing that is charac- teristic, unless, indeed, we attribute importance to the isolated observation of croup-like pseudo-membranes in the larynx and trachea of one patient. Ordinarily we find in the respiratory organs only the signs of a more or less intense, simple inflamma- tion—namely, swelling, loss of epithelium, redness, and some- times scattered superficial ulcers. The oesophagus and stomach 1 Crichton-Brown, Lancet. 1868. i L'Union med. 1857. 366 BOEHM.—POISONS. are similarly affected ; the visible local destructions caused by the ammonia scarcely ever extend beyond the stomach. A purely symptomatic treatment is the best to pursue. When caustic ammonia has been taken, and the case is seen immedi- ately, the administration of diluted acids is indicated theo- retically, and has frequently been put in practice. As a rule, ordinary vinegar, which is to be found in every house, is used, or sometimes lemon juice ; both should be given in a very diluted form. At a later stage, this antidotal treatment is of course use- less. Moreover, the dysphagia of the patient always presents an obstacle to its employment. To the use of the stomach-pump there is no special objection, but emetics must be avoided. The French authors have repeat- edly used local blood-letting, such as leeches on the neck and epigastrium, according to their own accounts, with good results. When the dyspnoea is very severe the question of tracheotomy will of course present itself. The treatment of the other symptoms does not require an extended consideration; it must be regulated according to the general laws. CHAPTER II. POISONING BY CAUSTIC AND CARBONATED ALKALIES (POTASSIUM AND SODIUM). Although the difference in the constitutional action of potas- sium and sodium salts has in recent times been very positively demonstrated, we can still treat of them both together when their local caustic effects come into question; for in this respect no difference can be detected in their action. The poisoning in question here closely resembles in its nature that produced by the concentrated acids. At most it presents a few noticeable modifications as regards the intensity of the phe- nomena and the course. The caustic alkalies also, the chemical properties of which Ave assume to be known, are chiefly dangerous to the animal tissues CAUSTIC AND CARBONATED ALKALIES. 367 on account of their affinity for water. To a less degree, their behavior towards the free acids in the tissues and the acids com- bined with weaker bases, as well as towards the albuminous substances, comes into question; all three are deprived of their functions in the organism by an excess of these alkalies. Upon these chemical reactions, which take place immediately at the point of contact, depends their caustic action. On the sensory nerves contained in cauterized spots they act as violent irritants, and thus provoke intense pain ; the parts surrounding these spots react by developing inflammation. The high diffusive power of the alkalies in solution is exceptionally favorable to the extension of their caustic action into the deeper layers of the tissues. The acids, when in a concentrated form, convert the tissues into discolored, dark, tinder-like masses, but the caustic action of alkalies produces less discolored, greasy masses resembling salve. When the alkali meets with tissues containing much fat, a soap is formed. The action of the carbonates of the alkalies is very similar to that of the caustic ; the carbonic acid, being but feebly combined, is easily displaced when they come in contact with the secretions of the stomach. The toxicological importance of the substances here discussed is not very great. Cases of poisoning by them, as a rule, oAve their existence to accident. Being much used in manufactures, they are readily accessible to every one. Cases of poisoning occur not only from potash and soda lye, but sometimes also from soap-water, which always contains free alkali. Several cases of this sort have resulted from the substances designated being mistaken for purgatives. Tardieu1 also reckons the eau de javelle, which is a solution of sodium hypochlorite,2 among those substances Avhich act in the same way as the free alkalies, and mentions cases which afforded the characteristic phenomena of poisoning by lyes. Here, however, a part of the action should properly be ascribed to the chlorine. Casper3 reports a case of attempted murder by soda lye, and Tardieu -describes two cases 1 Loc. cit. p. 234. 2 See previous note (p. 288). 3 Loc. cit. II. p. 493. 368 BOEHM.—POISONS. where potash lye and potassic carbonate respectively served for suicidal purposes. In the literature we could find in all only eighteen cases of this form of poisoning. Of these five were caused by potash,' two by soda lye,5 seven by potassic carbonate,3 one by soap-water, and three by eau de javelle.4 Fifteen cases terminated fatally, and only three in recovery. With respect to the toxic and fatal dose, no satisfactory con- clusion can be deduced from the material at our command. Tardieu (loc. cit.) holds that from two and a half to five drachms of sodium or potassium hydrate is sufficient to cause death. The fatal cases that are reported in the literature of the subject are of little value in this connection, because in almost all of them the concentration of the solutions used is unknown. The symptoms of poisoning by lyes differ from those caused by acids only in intensity. The repulsive taste of the liquids, and the severe pain that is experienced immediately when they are very concentrated, as a rule cause the poison to be spat out at once, so that in all cases only a comparatively small quantity reaches the stomach. This organ instantly reacts by violent vomiting. Loss of conscious- ness and convulsions, symptoms of reaction on the part of the nervous system, which are so frequently observed in sulphoxysm, occur only exceptionally in poisoning by lyes.6 On the other hand, the pains in the pharynx, oesophagus, stomach, and epigastric region are not much less severe than in the case of poisoning by acids. Loss of the power of speech and extreme dysphagia are also seldom absent. The visible portions of the mucous membrane of the mouth and throat are more or less altered; sometimes they merely assume a bright-red color, but again they are covered with a brownish film, and are entirely denuded of epithelium in spots. 1 Beutsch (Preuss. Ver.-Ztg. 1857), Boudet, Behier (Tardieu. loc. cit.), Dewar, Pallas (Frank's Magaz. III.). >l Casper (loc. cit.), Tjeischmann (Jahresber. v. Virchow und Hirsch. 1867). 3 Dewar (loc. cit.), Liegard (Frank's Magaz.), Orfila(loc. cit.), Barclay (Taylor, loc. cit.), Tardieu (loc. cit.), Espagne (Arch. gen. 1867). 4 Tardieu, loc. cit. 6 Liegard, loc. cit. CAUSTIC AND CARBONATED ALKALIES. 369 The vomit has at times a greasy, salve-like consistency, and is seldom bloody; its alkaline reaction has been frequently demon- strated ; in very severe cases shreds of necrotic mucous mem- brane are thrown up. Intestinal symptoms are, as a rule, Avant- ing. The constitutional symptoms are similar to those of a moder- ately severe case of acid poisoning, and require no detailed account. We will speak later of the specific action of potassium ; in poisoning by lyes it scarcely ever manifests itself in an unequiv- ocal manner. The patients usually recover from the immediate effects of the poison when this consists of lye, but very frequently a chronic affection is left behind, which may prove fatal months after- wards. In ten of the above-mentioned eighteen cases strictures of the oesophagus were developed, which led to inanition. The chronic inflammation which causes these cicatricial strictures is usually located in the loAver third of the oesophagus. In one case a large abscess formed, which discharged into the oesopha- gus, and opened a communication between it and the right pleural' sac. It is not necessary to describe in extenso the symptoms caused by these secondary disorders. A simultaneous affection of the lungs (pneumonia) was observed in Casper's case ; it evi- dently resulted from the local irritation produced by the pene- tration of some of the poison into the air-passages. The pathologico-anatomical examination demonstrated, with- out exception, the limitation of the lesions to the mouth, phar- ynx, oesophagus, and stomach; they never extended into the intestines. Even in the stomach we find, as a rule, only a feAv small ulcers, or their residua. In cases which had run a chronic course we find, in addition to the cicatricial strictures, all the signs of inanition—namely, emaciation, anaemia, atrophy of the gastric walls and of the muscular coats of the intestines, etc. In the treatment of poisoning by lyes, the indicatio causalis 1 Leischmann, loc. cit. VOL. XVII.—24 370 BOEHM. —POISONS. is fulfilled by removing any of the poison remaining in the stomach by means of the stomach-pump. Besides this, a liberal administration of acid drinks (vinegar, lemonade, and the like) is to be recommended; otherwise the management of the case must be purely symptomatic. A judicious treatment of the cicatricial strictures with bou- gies, together with careful feeding, has brought about a favora- ble result in several chronic cases. Caustic lime plays a still more subordinate role in toxicology than the alkalies. The disorders which are produced by its external action must, of course, remain unconsidered here. Quick as well as slaked lime acts in a similar manner to the other alkalies, and when introduced in large cpuantities into the stomach may provoke gastrointesti- nal symptoms. In the literature but three cases1 of poisoning by this substance are recorded. They present no points of special interest. The poisonous qualities of the soluble lime salts (calcium chloride), which were determined by Blake2 and others, by experiments on animals, have been verified by researches instituted by Mickwitz and the author. CHAPTER III. POISONING BY SALTS OF THE ALKALIES AND EARTHS (ESPECIALLY POTASSIUM NITRATE). All the salts of the alkalies and earths that are soluble 3 in water, Avhen introduced into the system in considerable quanti- ties, provoke disturbances which vary according to the diffusive power of each combination, and hence must, in a certain sense, be regarded as local effects. The nature of the base has no influ- ence in the production of these effects. For instance, the salts 1 Timaeus (Christison, loc. cit.), Gmelin (Gesch. d. Mineralgifte), Lion (Frank's Mag. I. p. 209). 2 Loc. cit., Edinb. Med. Journ. 1841. 3 We except, of course, those salts which exert a specific poisonous power, by virtue of their acid (potassium cyanide, alkaline arsenites and arsenates, etc.). These will be treated of under the heads of the poisons which they contain. The alkaline sulphides also must be considered under sulphuretted hydrogen, and the hypochlorites under chlorine. ALKALINE AND EARTHY SALTS. 371 which are only slightly diffusible provoke diarrhoea, while those which are readily diffusible cause diuresis. AVhen administered in large quantities in the solid form or in highly concentrated solutions they all act as caustics by the abstraction of water, and produce gastro-enteritis. Apart from these local effects the bases of certain of these salts possess more or less decided specific poisonous qualities. Of the more common of these bases sodium is the only one that has so far proved to be absolutely innocuous. The poisonous nature of potassium has recently been absolutely demonstrated, while that of barium has long been known. Lime and magnesia, although up to the present time they have had no toxicological importance, must, in accordance with the results of experiments, also be classed as poisonous, while strontium, like sodium, is innocuous. On the whole, however, the specific poisonous quality of these substances manifests itself unmistakably only Avhen they are introduced directly into the blood in large quantities. Such quantities as are absorbed from the intestines, as a rule, do not suffice to produce these so-called constitutional effects. Of all these substances barium—which will be considered at length in another place—is unquestionably the most poisonous. The po- tassium compounds come next, Avhile lime, magnesia, and stron- tia probably never produce constitutional effects Avhen absorbed from the stomach. We shall confine ourselves here to the discussion of poisoning by potassium nitrate. While speaking of it in particular, Iioav- ever, the opportunity presents itself to indicate the local effects which are common to most of the salts, apart from the specific action of the potassium. Although even the older observers noticed a difference in the ac- tion of sodium nitrate and potassium nitrate, and although Blake in his experiments—to which hitherto very little attention has been paid—attained results which proved potassium to be exceed- ingly poisonous, this fact, nevertheless, was not generally admitted until the year 1864. It was chiefly the experiments of Grandean' 1 Journ. de l'anat. et phys. 1864. 372 BOEHM.—POISONS. and Traube' which led to its universal acceptance ; and by a natural reaction its importance soon became greatly overesti- mated. In respect to their absorption and elimination, and their chemical behavior Avhile in the blood, the potassium salts differ in no respect, as far as can be determined, from the other soluble salts. The certainly striking brightness of the arterial blood, which is invariably observed in animals poisoned by potassium salts, cannot as yet be utilized in any Avay. The knotty point about potassium poisoning consists rather in the numerous re- markable and absolutely inexplicable effects which the substance produces upon the functions of the heart and the nervous system, in spite of its being itself an integral constituent of the body. The potassium salts, when introduced in considerable quanti- ties directly into the blood of either cold-blooded or warm- blooded animals, stop the movements of the heart.2 Cold-blooded animals are, before this occurs, deprived of the power of volun- tary motion, while warm-blooded animals, after the cessation of the heart's action, die in more or less developed convulsions. Traube (loc. cit.) compared the action of potassium on the heart to that of digitalin, and emphasized particularly the analogous influence of both substances on the blood-pressure. However, this correspondence in the action of potassium and digitalin can hardly be proved satisfactorily. Bunge's3 experiments on cats and dogs did not confirm Traube1 s statements cencerning the blood-pressure. Moreover, Mickwitz4 and the writer have never seen the blood-pressure increase after poisoning by potassium in animals which had not been curarized ; on the other hand, an increase in the pressure invariably ensued after previous poison- ing by curari. The study of the behavior of the cardiac nerves in mammals has contributed just as little towards explaining the nature of the paralyzing action of potassium on the heart as have the ex- 1 Ges. Abhandlung. I. 2 Guttmann, Berl. klin. Wochenschr. 1865. Virch. Arch. XXXV. Podcopaew, Virch. Arch. XXXIII. 3 Pflueger's Arch. 4 Inaug.-Dissert. Dorpat. 1874- ALKALINE AND EARTHY SALTS. 373 periments on frogs. Still the investigations1 which the writer instituted in connection with Mickwitz have opened up to him some new points of view. He found that the paralysis of the heart produced in mammals by the potassium salts is only ap- parent, and that by patient persistence in artificial respiration, and by mechanical irritation of the heart (compression of the thorax) the action of the heart can be entirely restored. Since animals which had already lain for thirty-eight minutes apparently dead, and entirely without pulsation in the heart, were completely restored to life by these means, it is evident that the potassium cannot possibly occasion a profound alteration in the physiological condition of the heart. It is more probable that the effects produced by it are due to temporary anomalies of excitability in the automatic central organ of the heart. After the awakening of the heart from its apparent death, it shows a striking increase of energy in comparison with its action before the poisoning ; this manifests itself both in the frequency of the pulse and in the blood-pressure. These striking facts are not altogether without parallel, since a frog's heart, when its pulsations have been stopped by the action of potassium, can again be set in operation by mechanical irritation, and its con- tractions are then remarkably energetic. The effects produced by potassium on the rest of the nervous system consist in a transitory stage of excitement, which is fol- lowed by general paralysis ; more or less general clonic spasms precede the paralysis both of the motor and the sensory centres. Respiration does not cease until after the heart's action stops. After awaking from the apparent death, the respiratory mus- cles do not regain their power of spontaneous movement until some time after the heart has resumed its action ; the animal is still in a state of total narcosis, and does not respond to irrita- tions of any kind. After the lapse of considerable time the reflex actions gradually return, and then an abnormal increase in the reflex excitability is frequently observed. This increase in the reflex excitability may be so great, that even trifling causes (a 1 Compare Centralbl. f. d. med. Wissensch. 1874. Ueber Wiederbelebung nach Ver- giftungen. 374 BOEHM.—POISONS. shaking, a gentle touch on the surface of the skin) may cause spasms. The local effects produced by the potassium salts on the stomach and intestinal canal are essentially similar to those produced by all other analogous combinations ; they consist in a gastro-enteritis, which varies in violence according to the size of the dose. Cases of poisoning by potassium nitrate are not very frequent. In the majority of cases they arise from mistaking this poison- ous salt for the common purgative salts (Glauber's and Epsom salts). The following small table gives the most important points of all the cases that are to be found in the literature : Result of the Poi- Cause. Observer. soning. Recovery. Mistake. Oberstadt. Recovery. Mistake. Deutsch. Death in 5 hours ? Jour. d.Chimie Death. Mistake. - Mouton. Recovery. Mistake. Rust's Magaz. Death. Mistake. Laflize. Death. ? Jouville. Recovery. Mistake. Buttler. Recovery. Mistake. ? Death. Clyster. 0. A. Meyer. Recovery. ? Ritter. Death. Mistake. Chevallier. Recovery. (Abortion.) Mistake. Alexander. Th,e figures here given demonstrate the impossibility of deter- mining with accuracy the fatal dose for human beings. The symptoms of poisoning by nitre begin usually with vio- lent purging and vomiting, combined with severe pains in the epi- gastric region and the abdomen. In rare cases the masses ejected by vomiting are bloody. To these phenomena coldness of the extremities, cold sweat, and sometimes also painful strangury and tenesmus are very soon added. The pulse is frequent, small, and irregular ; the respiration sometimes labored. The constitutional phenomena which are due to the action of potassium were unequivocally present in five of the above-men- tioned thirteen cases. They consisted in a feeling of intense No. Sex and Age oE Individual. Quantity of Poison. 1 2 3 4 5 6 7 8 9 10 11 12 13 Man 50 Man 30 Man ? Man 20 Girl ? Woman 48 Woman 36 Woman ? Woman 24 Man 40 Man 1 ? Woman ? ^ (pregnant) \ 3 VI. 1IIL Si. Si-Si. Si-s»-3". Sss. 3 vjss. A handful. BARIUM COMPOUNDS. 375 anxiety, pains in the back, spasmodic contraction of certain muscles (pectorals, calves of the legs), aphonia, general convul- sions, loss of consciousness, and coma. In Mouton's case, the local phenomena were said to have been entirely absent. Death ensued in from five to sixty hours. Among the symptoms which occur only in special cases, we may mention abor- tion, which was observed in Alexander's case; also peculiar choreic movements, which, in another case observed by Buttler, that of a pregnant woman, are said to have continued for two months after the poisoning. Sometimes recovery takes place very gradually, various nerv- ous symptoms (twitchings, neuralgic pains, etc.), as Avell as dis- orders of digestion, persisting for a long time as secondary effects. The pathological appearances at the autopsy are limited to the frequently described lesions of gastro-enteritis. The treatment is purely symptomatic. When the patient is asphyxiated or comatose, we must, in accordance with the knowl- edge gained from experiments on animals, recommend the ener- getic employment of artificial respiration, with compression of the thorax in the region of the heart. CHAPTER IV. POISONING BY BARIUM COMPOUNDS. As regards poisonous qualities, the barium compounds hold unquestionably the first place among the salts of the alkalies and earths. Nevertheless, they are only of subordinate importance in practical toxicology, because cases of poisoning by them are of exceedingly rare occurrence. Barium carbonate and chloride are the only preparations which must be considered in this connection, and the chloride (terra ponderosa salita), in consequence of its solubility in water, is absorbed without any further change, and acts as a poison, not only when taken into the stomach, but also when injected into the subcutaneous cellular tissue or into wounds ; the carbonate, on the other hand (baryta carbonica, witherite), being but little 376 BOEHM. —POISONS. soluble in water, is only poisonous in so far as it can be trans- formed into soluble combinations (barium chloride) in the diges- tive fluids. Experiments on animals by different authors have, moreover, proved that all the other soluble barium salts possess a like poi- sonous power. The passage of the barium combinations into the urine has been regarded as proved by the observations of Krahmer and Orfila ;l no recent investigations of this point have been reported. Barium is reckoned among the poisons Avhich exert a local irritating as well as a constitutional action; evidently only because among the symptoms of acute barium poisoning vomit- ing and diarrhcea are seldom wanting. Since, however, the anatomical lesions characteristic of local irritation are usually absent, and since the symptoms ascribed to it are also, as it appears, observed after the direct introduction of the poison into the blood, we see no grounds for endorsing the assumption that barium exerts a local irritating action. Very large quantities of the substance will of course produce the local effects which are common to all salts. Concerning the real cause of the poison- ousness of the barium compounds Ave are absolutely ignorant. The surmise of Onsum,2 that the poison is converted in the blood into an insoluble sulphate, which in a purely mechanical manner produces emboli in the lungs, has been confuted by Cyon.3 Judging from the symptoms, the action of barium must be compared to that of the narcotic poisons. The experiments made upon animals prove that the poison exerts an undoubted influence on the circulatory apparatus. Even the older toxicologists called barium a heart poison,4 and Cyon (loc. cit.) has recently demonstrated this property of the poison by experiments on frogs and rabbits. In mammals the cessation of the heart's action after the administration of barium has been observed by numerous 1 See Husemnnn, Toxikologie. 2 Virch. Arch. Vol. XXXVIII. 3 Arch. f. Anat. u. Physiolog. 1866. 4 Orfila (loc. cit.), Brodie, Blake, and others. BARIUM COMPOUNDS. 377 authors; some have even emphasized the lack of excitabil- ity shown by the paralyzed heart when irritants are applied to it. The investigations recently undertaken by Mickwitz,1 under the direction of the writer, have defined somewhat more precisely the nature of this cardiac paralysis. Although it is not possible to determine from them whether this paralysis is confined solely to the cardiac nerves, or affects also the muscles of the organ, still, the cessation of the heart's action during systole has been sliOAvn to be a constant phenomenon both in warm and cold- blooded animals: in mammals (cats) especially, the cartilaginous consistency of the left ventricle is striking. In this connection the parity of action between barium and digitalis can hardly be overlooked. The blood-pressure increases enormously after the injection of small quantities of barium solutions into the veins, but the increase is, as a rule, preceded by a not inconsiderable lowering of the pressure. The increase often occurs very sud- denly, and the pressure not infrequently becomes three or four times as great as before; at the same time the pulse becomes much more rapid. Increasing the dose then causes a steep sink- ing of the pressure-curve, and paralysis of the heart. Division of the spinal cord in the neck does not at all interfere Avith the development of this phenomena, and hence it does not appear improbable that the muscular coats of the vessels, as well as the heart, are affected by the poison. This hypothesis receives sup- port also from the state of excessive contraction into which, as our own investigations show, the smooth muscular fibres of the intestine and bladder are thrown by the poison. Both organs lose their lumina completely in cases of barium poisoning. This peculiaritjr, which has not hitherto been noticed by any other writer, and Avhich can be recognized even during life by the exceedingly active peristaltic movements of the intestines that are visible through the abdominal walls, seems to us to afford also a sufficient explanation of the alleged gastrointesti- nal symptoms (diarrhoea and vomiting). It indicates a certain preference of barium for the tissues composed of non-striated 1 Inaug. Diss. Dorpat. 1874. 378 BOEHM.—POISONS. muscular fibres, or for the nerves contained in them, which is characteristic of the action of the poison. In cold-blooded animals the other symptoms, caused by the action of the poison on the nervous system, consist in paralysis of the voluntary muscles, which is, however, preceded by a peculiar state of rudimentary, clonic spasms.1 Frequent tetanic spasms are seldom absent in mammals. The disturbances of the respiration are evidently dependent upon the anomalies of the circulation which precede them. Since in all the literature of toxicology, both old and recent, only very few cases of poisoning by barium compounds can be found, it may be assumed that this form of poisoning belongs to the rarities. In the feAv cases that have been reported the poison- ing Avas due to inappropriate medicinal use of barium chloride, or to the chloride or some other barium salt having been mis- taken for Epsom salts,3 Glauber's salts,3 sublimed sulphur,4 or Carlsbad salts.5 Once a powder for rats, consisting of barium chloride, was taken with suicidal intent ; finally, one case has been reported where temporary symptoms of poisoning occurred in a child who had cheAved a paper collar, in the coloring of which heavy spar had been used. The use of barium nitrate in pyrotechnics for the production of the so-called green fire might also cause poisoning, while the sulphate, which is used as a pig- ment on account of its insolubility, is almost innocuous. As for the toxic and fatal dose, no satisfactory figures can be given on account of the meagreness of the material at our com- mand. One drachm of the carbonate and half an ounce of the chloride have proved fatal to adults. However, these are not by any means the smallest quantities that may prove fatal. The clinical phenomena are composed of varying nervous and gastro-intestinal symptoms. Nausea, anxiety, and vomiting usu- ally open the scene ; these are followed by epigastric pains, pro- 1 Compare on this point the essay of the writer on Barium Salts. Arch. f. exper. Path. u. Pharm. 1875. III. 2 Wolf, Casper's Wochenschr. 3 Wach, Henke's Zeitschr. fur Staats-Arzneikunde. 1835. 4 Tidy, Med. Press and Circ., Jahresber. v. Virch. u. Hirsch. 1868. p. 325 L 5 Virchow u. Hirsch, Jahresber. 1867. p. 443. I. ALUM. 379 fuse diarrhoea, and severe colicky pains, which themselves usher in the nervous symptoms; ringing in the ears, diplopia, precor- dial anguish, weakness of the muscles, eccentric pains, cramps in the calves of the legs, and general convulsions. Loss of sensibil- ity and paraplegic phenomena have been observed in two cases. Among the more constant phenomena we must mention cold- ness and paleness of the skin. In one case mention was made of a full, hard pulse. The course of the poisoning was several times very rapidly fatal. Characteristic pathologico - anatomical lesions are lacking ; twice the signs of a gastro-enteritis toxica were observed, and once even perforation of the stomach was found. The treatment must be primarily directed to the removal of any of the poison that yet remains in the stomach. For this purpose the stomach-pump is the best means at our disposal. Emetics (apomorphia) may also be used. As chemical antidotes magnesium and sodium sulphates are recommended; they should be administered in large quantities of water. Otherwise the treatment must be purely symptomatic. The paralysis of the heart can sometimes, as is evident from our experiments on animals, be overcome by persistent irritation of the heart (forcible compression of the thorax and artificial res- piration) continued for several minutes. In desperate cases in men this mode of treatment, or even acupuncture of the heart, should not be left untried. CHAPTER V. POISON BY ALUM (ALUMEN). Alum, which is so extensively used in manufactures, the arts, and medicine, must, according to both ancient and modern expe- rience, be classed among the more powerful poisons. A double combination of potassium sulphate with aluminic sulphate pro- duces this salt, which is a colorless, crystalline, strongly acid substance ; it is readily soluble in water, and has a strong astrin- gent taste. 380 BOEHM.—POISONS. Mitscherlich has studied the action of alum upon albuminous substances, and has found that their solutions were precipitated by solutions of alum. The precipitate contains both alum and albumen, and hence, according to the current terminology, it is designated as alum-albuminate. The passage of alum from the stomach into various secretions has been frequently demon strated. The experiments hitherto made with alum have been under- taken solely Avith a view to determine the answer to the question Avhether it is really poisonous. Christison (loc. cit.) considers it almost absolutely harmless, and Orfila also (loc. cit.), on the occasion of a medico-legal investigation of a case in Paris, ascribed to it only a very trifling poisonous action. Although the experiments made, some of them by Orfila himself, have established the poisonous power of alum beyond question, noth- ing has been learned from them regarding the nature of its toxic action. Whether the active agent is free sulphuric add, as Tar- dieu1 thinks, or the potassium salt, or, finally, the alum as a whole and as a poison sui generis, cannot as yet be decided. The reaction of alum with albumen furnishes a simple expla- nation of the corrosive action of the salt in the solid form or in concentrated solution. The emetic action of the poison also, which we have learned both from Barthez's" experiments on himself and from the cases of poisoning that have been observed, might possibly be regarded as the consequence of a local affec- tion of the mucous membrane of the stomach. The great rapid- ity with which a case, recently observed by Ricquet,3 proved fatal, and some symptoms noted in previous cases of poisoning (tremor of the muscles, spasms, depression, etc.) give us reason to suspect that alum exerts also a constitutional action, the more so as in Ricquet's case the local lesions caused by the poison were found at the autopsy to be comparatively slight, and entirely out of proportion to the rapidly fatal course of the poi- soning. Tardieu (loc. cit.) speaks of a woman who wilfully murdered 1 Toxikologie. II. edit. 1875. 2 Frank's Magaz. III. 3 Journ. de Pharm. et de Chim. Oct. 1873. ALUM. 381 her three-months-old child by administering to it about 0.9 gramme (fourteen grains) of alum. In the majority of the other cases of acute poisoning the alum was taken by mistake for other medicinal preparations (e. g., magnesic sulphate, Ricquet). Von Hasselt states that cases of poisoning also arise sometimes from the administration of too large doses of alum by order of the physician. The sophistication of flour with small quantities of alum, which is much practised in England, appears to have no toxicological importance, although Snow' finds in it one cause of the prevalence of rhachitis. To the three cases of alum poisoning described by Von Has- selt, Taylor, and Husemann, Ave must add one case reported by Ricquet, and two cases by Tardieu (loc. cit.), all of Avhich ter- minated fatally. In the mentioned case of Tardieu, 0.9 gramme (fourteen grains), in that of Ricquet, 30 grammes (nearly one ounce) of alum Avere administered. Of all the symptoms the most constant are the pains in the cavity of the mouth, in the oesophagus and stomach, which are experienced immediately after taking the poison, and also the vomiting, which comes on very soon and is sometimes bloody. Ricquet also observed severe dysphagia, torturing thirst, and retention of faeces. Several writers mention great weakness of the muscles and depression. The consciousness is unclouded. There is great anxiety and sometimes a convulsive tremor of the muscles is observed. The pulse is exceedingly small and fre- quent. After repeated fainting-fits and after a considerable reduction of temperature beloAv the normal point, death ensued inside of twenty-four hours. At the autopsy, yellowish-gray deposits Avere found on the mucous membranes of the mouth, pharynx, and oesophagus; the tongue and palate were swollen. The stomach, intestines, and kidneys were hypersemic, but without noticeable loss of sub- stance. The chemical tests for the poison were repeatedly em- ployed successfully. No special rules for treatment can at present be laid down. 1 Husemann, Toxikol. SECOND PART. !X Poisoning by Anaesthetics and other Poisonous Carbon-Compounds. FIRST DIVISION. Poisoning by Anaesthetics. CHAPTER I. POISONING BY ALCOHOL—ACUTE AND CHRONIC ALCOHOLISM. Ethyl-alcohol (02HBOH), as a constituent of various fermented liquors (beer, wine, etc.), and spirits (brandy, rum, arrack, cognac, etc.), is one of the most widely diffused luxuries of civilized nations. Its useful or pleasant qualities do not now con- cern us. In these pages we only notice it so far as it proves inju- rious to health. The different kinds of alcoholic liquors are for the most part important in proportion to the quantity of alcohol they severally contain. It is only in a very few cases that the differences in their other qualities are of any importance. If we take any notice of their quality, it is generally because some other injurious ingredient accompanies the spirit of wine. To this category some not very important ethers, and absinthe, largely used in France, belong. Alcoholic liquors are often purposely adulterated, but these adulterations do not now con- cern us. Alcohol, free from water (anhydrous alcohol), is lighter than water, but freely miscible with it in all proportions ; it forms a colorless, volatile liquid, which burns with a blue flame. The vapor has a characteristic and agreeable odor, and alcoholic solu- ANAESTHETICS.—ALCOHOL. 383 tions have a pleasant taste, which is combined Avith an intense feeling of burning. Concentrated spirits of wine, or alcohol with but little admix- ture of water, acts upon animal tissues just like irritant corrosive poisons. This is very likely due to its strong affinity for wafer- tile less water it contains, the more eagerly will it attract AA-ater to itself. For the most part, however, in alcoholic poisoning, the local injuries are unimportant when compared with the general symptoms which spring from the absorption and recep- tion of the poison into the circulation—in other words, into the blood. Absorption may take place in several ways. Although not strictly proven, it seems highly probable (considering the remarkable poAver of diffusion possessed by alcohol) that it can be absorbed into the blood by absorption through the unbroken skin. Alcohol, in the form of vapor, is diffused into the blood from the internal surface of the lungs. It goes through the tissues of the mucous membranes, straight into the blood-vessels, mixed with water. Bouchardat and Sandras1 state that spirits of wine intro- duced into the stomach is almost all absorbed by the gastric veins (though the intestinal veins absorb some), whilst none of it will be taken up by the lymphatics and lacteals. Lastly, alcohol may be absorbed by the surface of suppurating wounds ; indeed it is not very uncommon to note a good deal of drunkenness after the application of spirit lotions 2 or spirits of camphor to the stump of an amputated limb. Alcohol is eliminated from the body by three channels: the air expired from the lungs, the urine, and the skin. Although it had long been suspected from the smell of the breath that alcohol was eliminated by the lungs, this has of late years been determined experimentally by Lallemand, Perrin and Duroy,3 and by Parkes and Wollowicz,4 avIio have proved by indisputa- ble chemical tests that alcohol can be detected in the air breathed out from the lungs of healthy men who have taken 1 Annal. de Physique et Chimie. 1847. 2 See Chedevergne, Bullet, gen. de therap. LXVII., and Peronne, De l'alcoolisme dans ses rapports avec le traumatisme. Paris. 1870. 3 Du role de l'alcool et des anaesthesiques, etc. Paris. 1860. 4 Proceed, of the Royal Soc. Vol. XVIII. p. 362. 384 BOEHM.—POISONS. alcohol. The same experimenters discovered alcohol in the secretions of the skin. It has also been recovered from the urine by distillation, not only by Lallemand, Perrin and Duroy, but also by Baudot1 and Schulinus,2 although only in small quantities. It is by no means equally clear how the alcohol that is retained in the system is disposed of; in other words, Avhat becomes of the alcohol not eliminated as such is not so easily settled. The hypothesis propounded by Liebig,3 and at one time generally accepted, that alcohol in the blood and in the tissues undergoes combustion, and is converted into carbonic acid and water, and by its mere presence hinders the combustion of other materials of far greater importance in the organism (lessens tis- sue-changes), has not been confirmed by experiments any more than the assertion of Duchek4 that aldeb^d and oxalic and ace- tic acids are formed in the body out of alcohol. Both Masing,5 who worked under the supervision of Buchheim, and Lallemand, Perrin and Duroy sought in A'ain to discover these bodies in the blood after alcohol had been introduced into the stomach. These authors conclude from this, and from the fact that unde- composed alcohol can be detected in the blood and in most of the organs of the body, that alcohol passes through the system without undergoing any changes or decomposition. The French authors even go a step farther, and maintain, on the basis of quantitative determinations, that alcohol may be retained, and even accumulated, in certain organs, such as the liver and the brain, by reason of a sort of affinity for these organs, and retained a long time. It would seem, ho\vever, from the re- searches of Schulinus [as Avell as from those of Dupre and Anstie —Trans.], that this opinion is based upon errors inseparable from the mode of analysis employed by the French experimenters. 1 L'Union Med. 1863. 2 Inaug. Dissert. Dorpat. 1865. 3 Thierchemie. III. Aufl. S. 59. Booker (Beitrage zur Heilkunde. I. S. 258) was one of the very first to combat this view energetically, and has shown in himself that the excretion of carbon dioxide is considerably lessened by the ingestion of alcoholic drinks. 4 Prager Vierteljahrschrift. 1853. 6 Inaug -Dissert. Dorpat. 1854. ANAESTHETICS.—ALCOHOL. 385 Schulinus differs from Lallemand, Perrin and Duroy, in so far as he feels compelled to admit that there is a partial destruction or decomposition of alcohol in the blood ; because, if Ave kill an animal soon after its ingestion of alcohol, only a fractional part of that alcohol can be recovered, either from its excretions or from the blood itself, or from the organs of the animal. What kind of decomposition goes on, he could not, however, deter- mine ; and this question still remains undecided. As regards the behavior of alcohol in relation to the various constituents of living organisms, our first thoughts, almost of necessity, turn to its power of coagulating albuminous solutions. But though strong alcohol is one of the most certain means of precipitating the majority of albuminous substances, yet we may pretty safely assert that its physiological action, and, indeed, its action when introduced in moderate quantities into the blood itself, is not that of coagulation. Alcohol produces precipitates in gastric juice, and in solutions of peptone. In a living frog one can clearly see a dark coloration of the circulating blood soon after the introduction of two cubic centimetres (about 3 ss.) of alcohol into one of the lymphatic hearts, or into the cavity of the peri- toneum. But in mammalia and in human beings no change recognizable by our present methods of observation is brought about by the introduction of alcohol. Bonwetsch' states that, in ox-blood diluted with water, the reduction of the oxyhsemoglo- bin by stannous oxide soda solution occurs more slowly after the addition of alcohol than it does Avhen no alcohol is present. This fact seems to show that the poison has some affinity for oxyhaemoglobin. The alcohol which circulates with the blood modifies the normal course of organic functions in various AA^ays. The outward symptoms or phenomena, which are the expression of these disturbances, are like those induced by other narcotics. The nerve-centres, to Avhich the poison has access, have their functions stimulated and increased at first, and then their activ- ity is gradually more or less perfectly abolished for the time. These effects are much modified by the different quantities of the poison taken, and by the time during which the poison 1 Inaug.-Dissert. Dorpat. 1869. VOL. XVII.-25 386 BOEHM. —POISONS. works, so that we get a variety of phenomena, in Avhich some- times only the stage of excitement, sometimes only the paralytic stage, or both successively, in singular combinations, are pre- sented to us. The extent to which alcohol affects the nervous system is by no means restricted. Its domain is a wide one. If the results are at first limited to the cortical portion of the brain in the first instance, they may gradually extend so as to embrace almost all the central organs ; the centres for motion and sensa- tion, and for consciousness, the medulla oblongata and the spi- nal cord may all be involved in the action of this poison. Again, alcohol must be ranked with those narcotics which, after long-continued use, leave behind them permanent and en- during changes in the bodily organs. These changes may not always be recognizable by the minute anatomist, but they may be knoAvn very unequivocally by persistent anomalies of func- tion. We know that the system accustoms itself to the poison. In other words, a certain tolerance is established, so that doses originally potent gradually cease to produce the same effect upon the nerve-centres. As the poison is the same as it ever Avas, this tolerance must be founded in a permanent change in the vital activity of the organs concerned. Besides its action on the nerv- ous system, or animal life of the individual, alcohol has most indisputably an influence on the vegetative life. It affects the circulation and the processes of nutrition. Every-day experience teaches us that the habitual moderate enjoyment of alcohol encourages a tendency to corpulence. Liebig, who asserts that Ave have here a diminishing of the processes of oxidation, has explained this fact by the well-known hypothesis Ave have quoted above. But there are other facts which force us to conclude that alcohol most powerfully affects the metamorphosis of tissues. There is a long series of authors who have noted, though not Avith all the scientific accuracy desirable in such matters, that the excretion of carbonic acid is diminished after the use of alco- hol, v. Boeck and Bauer1 have recently established this fact in dogs by an experimental method which seems free from objection. There is, however, this limit, that only small quantities of alcohol 1 Zeitschrift fur Biologie. X. 1874. ANAESTHETICS,—ALCOHOL. 387 diminish the excretion of carbonic acid. Larger doses, on the contrary, considerably increase this excretion. The latter cir- cumstance is explained, according to v. Boeck and Bauer, by the great state of muscular excitement and jactitation (Muskelun- ruhe) into which the animals were thrown by larger doses. These authors believe that we should see diminished excretion of car- bonic acid, even after large doses of alcohol, if we could do away with the increased muscular movements; and if, as happens in human beings, large doses of alcohol were followed by deep sleep. The experiments of Boecker (loc. cit.) and Rabuteau1 are equally in favor of the view that alcohol diminishes tissue- changes ; for they found that the excretion of urea was also diminished by the use of alcohol. To the same effect are a long series of observations on the effects of spirits of wine on the temperature of the body. Unfortunately, many of the observa- tions are wanting in that nicety of observation which could enti- tle them to rank with those facts which may be considered as placed beyond dispute. Still, sufficient is known to indicate the direction in which our inquiries may be extended. If all these observations relating to the excretion of urea and carbonic acid and the lowering of temperature should be confirmed, there could scarcely be room for doubting any longer that alcohol diminishes the forces concerned in tissue-metamorphosis. Bonwetsch's dis- covery of the retardation of [the changes in] oxyhemoglobin by alcohol would then afford a satisfactory explanation of the whole affair. It is only when large and poisonous doses of alcohol are taken that the tempera- ture of the body is very sensibly depressed, so as to amount to several degrees of the Centigrade (100°) scale. With moderate doses the reduction of temperature is far less, and scarcely amounts to 1° Centigrade (1.8° Fahr.). Obernier,2 and Parkes, and Wollowicz (loc. cit.) were scarcely able to demonstrate any effect on tempera- ture from small doses of alcohol. Whilst Dumeril and Demarquay,3 Lallemand, Perrin, and Duroy (loc. cit.), Rage,4 Bouvier,5 Mainzer,6 Sulzynski,7 Daub,8 and Riegel,9 all observed slight falls of temperature. 'L'Union med. 1870. 6 Inaug.-Diss. Bonn. 1870. 2 Pfliiger's Arch. 1869. II. 'Inaug.-Diss. Dorpat. 1865. 3 Archiv. general. IV. S6r. XVI. 1848. 8 Med. Centralblatt. 1874. * Virchow's Archiv. Bd. 49. 1870. » Archiv fiir klin. Med. XII. 1874. 0 Pharmak. Studien liber den Alkohol. 1872. 388 BOEHM.—POISONS. Alcohol has also unmistakable effects on some of the organs of vegetative life. Its influence on the movements of the heart is placed beyond doubt, as regards human beings, by the experi- ments of Parkes and Wollowicz (loc. cit.); and as regards ani- mals, by the experiments of Zimmerberg (loc. cit.). This influ- ence is at first a considerable increase in the energy of the heart, which soon becomes greatly diminished. How far the different cardiac nerves are severally concerned cannot be settled off-hand. It is quite clear also that the vascular system is not exempt from the action of alcohol. The reddening of the skin, as well as the sinking of the blood-pressure after the injection of large quanti- ties of alcohol, both point to a considerable diminution of the tone or tension of the arteries (arterial tonus).1 There is a pretty generally diffused opinion that alcohol, in a reflex manner (by irri- tation of the sensitive nerves), excites and increases the secretions. It is in this Avay that it is credited with improving digestion. Nearly all our text-books of medicine speak of increased secretion of gastric juice as one of the effects of alcohol. But Claude Ber- nard' s experiments 2 have shown that strong alcohol has exactly the contrary effect. In other words, it brings about a diminution of all secretions, Avhilst they are but very slightly increased by very dilute spirits of wine. This is very strikingly so as regards digestion. Claude Bernard found that he could check digestion in the stomach of a dog in whom that process had commenced, by introducing alcohol into the stomach; and if alcohol and food were given together, digestion began a little later than in animals who had taken no alcohol. The secretion of gastric juice is therefore almost entirely suspended for a time by spirits of wine. Bernard has demonstrated the same as regards the activity of the secreting glands of the intestines. The excretory functions of the kidneys are decidedly increased and accelerated by the ingestion of moderate quantities of alcohol. Even the laity are familiar with the diuretic action of alcoholic liquor. The local action of spirits of wine may be partly explained by 1 Compare on this point Parkes and Wollowicz, Zimmerberg (loc. cit.) and Tscheschi- chin, Archiv fiir Anat. med. Phys. 1866. - Lecons sur les effets des substances toxiques, p. 414. ANAESTHETICS.—ALCOHOL. 389 the behavior of this substance with albuminous bodies, and by its affinity for water, of which we have spoken already. Its local action, however, must clearly be due in part to the direct contact of the alcohol with the terminations of the sensitive nerves. For instance, if the spirit be very strong and applied to certain parts, there is more or less of intense burning pain. There is then almost immediately (by reflex action after the irri- tation of the sensory nerves) dilatation of the blood-vessels and increased flow of blood to the part—symptoms which may, if the irritation be continued, go on to exudation and the forma- tion of sores, and may even go on to typical inflammation, just analogous to the effect of epispastics. As regards chronic alcoholic poisoning, or the effect of long- continued doses of alcohol, a number of experiments have been made on animals. Magnan1 fed some dogs for some months with alcoholic liquors, and he gradually saw symptoms analo- gous to those of chronic alcoholism in human beings developed in these animals. The dogs suffered from gradually increasing muscular weakness, general tremblings, and, especially during the night, from hallucinations (?), which were generally recog- nized by yelling out, hoAvling, and symptoms of extreme fear. They gradually sank from a sort of chronic marasmus. Kremi- ansky * instituted analogous experiments, in which he specially directed his attention to the development of a hemorrhagic pachymeningitis. Magnan's results in this direction were neg- ative. He thus differs from Kremiansky and Neumann,5 who were able to demonstrate the pathological changes mentioned above in the dura mater in dogs. The etiology of alcohol-poisoning is very closely connected with the abuse of spirituous liquors. The most popular of all methods of intoxication is simply acute alcoholic poisoning- drunkenness in its various degrees. Cases of chronic alcoholism must also be referred to the voluntary use of alcohol. It is indeed in very rare cases, and they are growing still more rarp, ' De l'alcoolisme des diverses formes, etc. Paris, 1874. ! Virchow's Archiv. 1868. XLII. 8 Inaug.-Dissert. Konigsberg. 1869. 390 BOEHM.—POISONS. that we see alcoholic poisoning produced either by pure accident, or from criminal motives. Mild forms of intoxication may indeed result from the common application of alcohol or spirits of cam- phor as a surgical application to wounds, as is commonly done in France. Schlesinger,1 indeed, noted a case of delirium tremens in a lady who used a great deal of eau de Cologne. [It is well known that this perfume is often mixed with water, and taken as a beverage.—Trans.] In consequence of the widespread use of alcoholic liquors as beverages, the baleful effects of this poison are not confined to individuals. They affect, and are felt by, whole communities. They are therefore deserving of notice, not merely from medical men, but from statesmen and political economists. Accurate statistics, which should show on the one hand the amount of alcoholism in different countries, and on the other side the dis- eases and crimes which are connected with or dependent upon it, would enable us clearly to see the enormous material and moral injury done by this poison. Unfortunately, much of the mate- rial is as yet uncollected. Enough has, however, been done on a small scale to give us an idea how such inquiries would be answered. In England, where special attention has been given to such questions, 75 per cent, of all crimes and 25 per cent, of insanity are closely connected with the abuse of alcohol. It is still worse as regards Ireland. It has been ascertained that in Glasgow every three-and-twentieth, in Liverpool every twentieth, and in Dublin every tenth person accused was found in a condi- tion of drunkenness. The consumption of spirituous liquors is generally larger in northern countries (Russia, Sweden, England, the north of Ger- many) than it is in southern countries (the south of Germany, Italy, and Spain). Hermann2 has given us some interesting ac- counts regarding Russia, and St. Petersburg in particular. The removal of the brandy monopoly in 1863 caused an enormous increase in the diseases which are due to alcohol. In the five hospitals of St. Petersburg, in the years 1861-1865, 3,206 1 Casper's Wochenscrift. 1835. " Petersburg med. Zeitschr. XIII. 2. 1867. ANAESTHETICS.—ALCOHOL. 391 patients were treated for alcoholism, or 1-3 per cent, of all the patients. Whilst in the years 1861 and 1862 (before the removal of the monopoly) some 26 and 23 cases respectively Avere fatal from alcoholism, these numbers rose, in the three years folloAving the removal of the monopoly,' to 33, 102, and 89. Of late years the consumption of the liquor called absinthe has reached enormous proportions, particularly in the large towns. The percentage of alcohol in the beverages consumed is naturally a point of special interest, for all those countries where the use of brandy prevails, afford, in consequence of this, a larger contingent of cases of alcoholic intoxication than those Avhere beer and other beverages poor in alcohol are the staple drinks. As regards the various ranks of society, the rule is that an overwhelming majority of drunkards is drawn from the lower classes—the proletariat and artisans. There are, hoAvever, no very accurate statistics on these points, and Ave know that drunkenness occurs far too commonly among the educated classes. Hermann says that in St. Petersburg the majority of drunkards are not taken from the very lowest class, but rather from the ranks of clerks and officials of the lower grades and small traders. In the year 1862, for example, among 109 alco- holic patients, 44 were clerks, 40 artisans, and only 20 day- laborers. In the year 1863 (in which the brandy monopoly Avas removed), among 297 patients, 107 were clerks, 99 artisans, and 32 day-laborers. It is easy to understand why the male sex is more commonly given to alcoholism than the female. (Of the 3,206 cases collected by Hermann, only 400 were women, or about one-eighth.) It is also natural that children and very old people less often suffer from alcoholism than people in middle life, or, in other Avords, between thirty and fifty years. Nothing definite can be laid down as regards the quantity of alcohol required to intoxicate, except as regards concentrated alcohol (over 50 per cent, in strength). As a rule, very small quantities of this are enough to bring on symptoms of poisoning in a very short time. In children, two tablespoonfuls of alcohol of 60 per cent, strength 392 BOEHM.—POISONS. has proved a fatal dose.1 In grown-up people not accustomed to stimulants, a larger quantity of rum or arrack (from one and a half to three fluidounces) will be required to rapidly produce symptoms of intoxication. Absolute alcohol (over 90 per cent. solutions), under all circumstances, even in small quantities, produces symptoms of poisoning by its local action. The symptoms and course of poisoning by alcohol are pecu- liar from the variety and complexity of the phenomena. In order to facilitate the study of these, we divide the sub- ject as folloAvs: I. Acute alcoholic poisoning, (a). Drunkenness (or mild form), (b). Poisoning by larger doses of alcohol (severe form). II. Chronic alcoholic poisoning, (a). Delirium tremens, (b). Chronic alcoholism. I. (a). Drunkenness. Familiar and well known as this con- dition Is, we must, for the sake of completeness, give a brief account of it here. The primary pleasant effect of moderate quantities of alcohol, and it is to these it owes its great popu- larity and extended use—is a sort of amiable (wohlthatig) altera- tion of common sensations—an exalted cerebration—more facile association of ideas—a feeling of increased bodily strength—and the banishment or vanishing of all previously present unpleasant sensations in the domain of both bodily and physical life. The expression to be "elevated" (angeheitert sein) capitally describes this condition, Avhich can scarcely in itself be considered an abnormal state (yet is so for the individual at the given time). Generally speaking, this condition leaves no unpleasant conse- quences behind it. The quantity and quality of the alcohol required to bring about this simplest form of poisoning varies greatly according to the individuality or personal character of those avIio take it. Only a very little more of the poison (alco- hol) requires to be taken, and the person already under its influ- ence is immediately lost to propriety. The state previously described is now greatly exaggerated. The man expresses his opinions more loudly and more freely, the tendency to put all his feelings into words becomes more and more uncontrollable, 1 DeutsclCs case. Preuss. Vereinzeitung ; quoted in Schmidt's Jahrbuch. Bd. XXV. ANAESTHETICS. —ALCOHOL. 393 and the cerebral centre, which should control his actions and his words—that "prudent, cautious self-control" which (according to Burns) is "wisdom's root," and gives to the sober the stamp of rationality, becomes weaker and weaker. The uncontrolled com- bination of ideas, the unfettered imagination, causes a flood of words, without arrangement, to roll over the tongue in a cease- less torrent. The hidden "I"—the whole man, willingly or unwillingly, comes to light, and the sober spectator and listener often gets unexpected glimpses of those depths of the soul's inner life which the man at another time would most anxiously screen from the gaze of the world around him. At the same time the excitation of the motor centres—the exaggerated ten- dency to action—often keeps pace with the general excitement, and urges on the drunken man to purposeless exhibitions of strength, often impelling him to seize hold of the living or lifeless objects which surround him. All the passions press to the front, without any concealment and with exaggerated intensity; love, hatred, revenge, fear, and anger lend their changing colors to the uncontrolled impulses which urge him on. But the over- strained bow is easily broken—often with a sudden snap. The hurly-burly is hushed, and the drunken man falls into a state of deep coma or narcotism. All the symptoms of excitement are weakened, and are succeeded by almost complete paralysis, and the over-stimulated and excited organs refuse to do their duty. This description, naturally enough, is not always accurate, but it pretty fairly represents the general s3rmptoms of intoxication. It is not possible, in our limits, to include all the varieties met AAith in practice. It must, however, be noted that in some cases the effects of alcohol are diametrically opposite, having a depress- ing effect upon the individual who takes it, even from the very first, making him reserved, tranquil, and even secretive, and he goes on to a state of narcotism without any of the ordinary out- ward signs of drunkenness. The amount of consciousness and rationality retained by the drunken man varies greatly, and is by no means always proportioned to the quantity of poison imbibed. Men who are manifestly drunk, often act and transact business, though perhaps only for a brief time, with complete reflective faculties and with a good deal of consideration. It is just the 394 BOEHM.—POISONS. same as regards the memory of what took place in the drunken state. No rule can be laid down, for some remember everything perfectly when they awake, others have no recollection of any- thing. The bodily condition during drunkenness, and the narcosis which follows, exhibit the following peculiarities : the face of the drinker becomes flushed and reddened, so do the ocular conjunctiva; the pulses beat more forcibly,' the skin is of ten profusely bathed in sweat, the frequency of the pulse is in- creased, and the pupils are, for the most part, contracted. The quantity of urine is generally increased and its speciflc gravity diminished, especially when much water has been ingested with the alcohol. The movements of the voluntary muscles, which were at first considerably increased in energy, become at a later stage decidedly less powerful, and a diminished power of co-ordination of movements becomes specially evident. The drunkard speaks stammeringly, staggers, and easily falls to the ground. It is very common to have repeated vomiting before narcotism sets in, but this symptom may be entirely absent. In the comatose condition, or full narcosis, the faculty of responding to external impressions—in other words, reflex action—is weakened in various degrees, and sometimes, in very deep intoxication, entirely lost. The dead-drunk man lies with relaxed and limp limbs, perfectly motionless, breathing deeply, but seldom. The pulse is now generally small and quick, the skin cool, and covered with clammy sweat. It is with great diffi- culty, if at all, that any sign of consciousness can be elicited by loud calls, shaking, sprinkling with water, or other modes of irritation. As a rule, he awakes spontaneously, after sleeping for a varying time, with different kinds of sequelae of his ex- cesses. Then he feels a severe, oppressive headache, finds it difficult to think, for his ideas are all at sixes and sevens; and at first he has scarcely any recollections of his recent debauch. Very commonly symptoms of acute gastric catarrh come on. Severe vomiting sets in, which often lasts for some days, and 1 Mendel (Virchow's Archiv. Bd. L.) found the temperature of the head, in drunk- enness, higher than that of the rectum. ANAESTHETICS. —ALCOHOL. 395 occurs several times in the same day ; he has complete loss of appetite, great thirst, an unpleasant taste in the mouth, and in addition, a great feeling of weariness and muscular prostration, felt all over the body. We have thought it better thus to sketch the general features presented by drunkenness, than to describe the spontaneous and often arbitrary varieties of one and the same condition under special names, and in great detail.1 Drunkenness is in its essence nothing else but a transient insan- ity. It may assume almost any form ; and indeed all the forms assumed by true insanity are imitated with great accuracy in a manner well worthy the study of those who devote themselves to psychology. Since the time of Percy,2 French authors have specially noted a form of drunkenness under the name of " convulsive intoxica- tion" (ivresse convulsive). It is distinguished from the ordinary kind by severe general convulsions and maniacal delirium. The attacks generally come on some hours after the person attacked has drunk heavily. They occur during sleep, and often without any clear symptoms of drunkenness having previously mani- fested themselves. Two powerful men could scarcely restrain the patients, Avho showed fight, and several of these attacks have ended fatally by the patients springing out of windows. In fact, t*he Avhole description is that of an acute attack of mania. The bodily condition differs very little from that common in the usual forms of drunkenness ; sometimes, however, general anaesthesia has been noted. According to Percy, this convulsive intoxica- tion may occur in very sensitive or "irritable" people, after any great excess of devotion to Bacchus ; but it is especially common after the use of new wine fortified with corn-spirit, or old wines adulterated in the same way. I. (b) The symptoms are, however, considerably modified in those cases where large quantities of strong alcohol are intro- duced into the system at one time. In these cases there is gene- rally no stage of excitement observed, but from the very begin- ning the signs of profound general depression of all the vital 1 Compare Falck, Intoxicationen, in Virchow's Pathologie und Therapie. II. 1, 2. 2 See Percy, Diction, des sciences med. t. XXVI., and especially Magnan (loc. cit.) and Lallemand, Perrin, and Duroy, loc. cit. 396 BOEIIM.—POISONS. functions are present. In this category most of the criminal cases of alcoholic poisoning will be found. Many cases are recorded in books and periodicals where children of a few months old, up to eight years of age, have been purposely killed in this way. There are also many analogous cases in grown-up people, who for the purpose of beastly gratification of appetite, have gone on imbibing strong spirits till they sank insensible to the ground. [Such cases are common in the docks, and are known as " sucking the monkey."—Tisans.] It is usual to find the per- sons thus poisoned in a state of deep coma and unconsciousness (sopor), with various degrees of general anaesthesia, with deep, ster- torous respiration, small, rapid, and easily compressible pulse, and, as a rule, dilated pupils, insensible to light. The skin of the face is generally reddened and bloated-looking, but some- times cyanotic ; the skin of the trunk and extremities cool and covered with clammy sweat. The mucous membranes of the mouth and throat may sIioav similar changes as in mild cases of poisoning by acids, especially a whitish coloration of the swollen and spongy epithelial lining. Vomiting, though often noted, is by no means a constant symptom. Many of the recorded cases mention the passage of thin, slimy stools, mixed with blood. In very young patients (children under three years of age), this sort of poisoning may terminate in death in a very few hours— it is, however, usual to find this preceded by general, or some- times purely local1 convulsions. The older the children are, the more likely is it that remedial measures will avert death. The symptoms in grown-up people are strictly analogous. Here, too, it is usual to find the patient in a condition of the deepest stupor; and in many of the recorded cases it is expressly stated that the patient fell down insensible whilst drinking. Conscious- ness is generally entirely abolished, and it is the same with sen- sation. The skin is cool, and the face and mucous membranes are cyanotic. If these dead-drunk people remain long on the ground in this condition, acute gangrene is sometimes seen on those parts of the skin most exposed to pressure. The epider- mis is first raised in blisters, which are filled with blood-stained 1 Thus, in the case previously quoted from Deutsch, convulsions were noted only in the right side of the body. ANAESTHETICS.—ALCOHOL. 397 serum, just as in burns, and the case may go on to the formation of a line of demarcation, and actual dropping off of portions of the body. The surrounding surface is highly cedematous, swol- len, and red, just as in phlegmonous erysipelas. Mitscherlich relates a case of this kind.1 The man fell down, and lay thirty hours with his left arm under him. The hand became gangrenous, and the whole of the left arm was highly cedematous, swollen, and reddened. In these cases, too, the breathing is deep, stertorous, and intermittent; the pulse small, and scarcely to be felt. The extremities are of marble coldness, and the temperature of the whole body is considerably lowered. In the most severe cases of this kind the pupil is dilated, and does not respond to light. In less severe ones, especially when some traces of consciousness are still present, the pupil is contracted to a pin's point. Burkitts describes a case, in which the previously contracted pupils dilated for a moment whenever the unconscious patient made attempts to speak. It is very common to find both the eyelids and conjunctivae with livid blood-spots (suggillirt). The eyeballs are sometimes very prominent and staring—sometimes deeply sunk in the orbits. Local symptoms of any disorder of the digestive organs are not usually much marked at first during the comatose con- dition—and begin to appear at a later stage, if the case have not ended fatally. In the mouth, except a very strong smell of alcohol, and a dry, fissured red tongue, covered with a thick fur or scab, there is notning very remarkable. Vomiting of blood, and stools containing blood have been noticed in a very feAV cases. Sometimes the stage of complete coma alternates with either furious or frisky delirium ; and convulsive movements of single groups of muscles, or extending over the whole of some region of the body, and even general clonic spasms, are not infrequently met with. The duration and course of these conditions are very varied, especially so as the treatment, or attempts at recovery, have been ' Virchow's Archiv. Bd. XXXVIII. 1867. 5 Dublin Medical Press. 1839. Quoted in Schmidt's Jahrbucher. 398 BOEHM. —POISONS. begun early or delayed till a late period. Loss of consciousness and coma may last several days, and may then terminate by the supervention of favorable symptoms, or may pass into a condi- tion very similar to delirium tremens. If no efforts be made at recovery for a considerable time, death may occur very easily in the first stage, in consequence of asphyxia and paresis of the heart. But death may also occur in the later stages. In the cases which begin to improve, the patients become conscious after some time, and then complain of violent headache and general weakness, and they labor for a considerable time under the symptoms of a more or less acute gastritis, which specially shows itself in frequent retchings and vomiting, pain in the epi- gastrium, total loss of appetite, and other symptoms of the same class. Post-mortem examinations of the bodies of those dying from acute alcoholic poisoning exhibit in some instances an exceed- ingly prolonged and remarkable resistance to putrefactive pro- cesses ; * but the opposite has also been noted, namely, an exceedingly rapid development of decomposition (compare Mitscherlich, loc. cit.). On those parts of the skin most subject to pressure during life (shoulders, nates, etc.) very large post- mortem stains or ecchymoses will be found ; sometimes the epi- dermis is raised into blisters, or there may even be more or less advanced bed-sores (decubitus). The mucous membrane of the digestive tract will sometimes have contents smelling plainly of the poison, while at other times there will be no trace of alcoholic odor. These mucous membranes will sometimes exhibit only redness and swelling, sometimes there will be ecchymoses, very seldom ulcers. Pennetier2 observed that ulcers were beginning to form in the lower part of the oesophagus and in the stomach in a fatal case of poisoning by alcohol. The mucous membrane of the respira- tory tract exhibits a widely-spread and intense injection of blood-vessels ; the lungs themselves are very often found in a 1 In the case previously quoted from Deutscli, in spite of a very hot summer no sign of putrefaction was found as long as thirty-six hours after death. s Theses. Paris. 1865. ANAESTHETICS.—ALCOHOL. 399 state of cedema ; still more frequently we discover in their poste- rior and inferior portions hypostases and hepatization. The smell of alcohol can nearly always be detected in the abdominal cavity. The same is affirmed of the cranial cavity, in which also serous exudations and great injection of the meninges are usually found. There are no other characteristic appearances in the brain. II. The condition known as general chronic' alcoholism exhib- its a variety of differing symptoms, Avhich sometimes alternate with one another. If we were to comprehend all the pathological changes which occur in notorious sots, we should have to make numerous subdivisions and distinctions in order to facilitate the study of a subject on which so many mistakes have been made by both ancient and modern writers. It appears to us essential to declare at the very onset that in a number of cases chronic alcoholism is perfectly identical with other forms of disease. In other words, that the poison of alco- hol, either alone or combined with other pathological causes, produces bodily or mental diseases Avhich in themselves afford nothing characteristic of the effects of alcohol. To this category belong many cases of imbecility, of paralytic dementia, and of melancholia, as well as of tabes dorsalis, atrophy of the liver, morbus Brightii, and other diseases which we often find de- scribed as special forms of alcoholism without any claim, in our opinion, to such a designation. We shall gain far more insight into the whole question if we start with the proposition, that besides the special diseases resulting from this poison, the habit- ual misuse or abuse of alcohol is one of those primary causes which combine together to generate a great many forms of dis- ease. In this place, however, we are chiefly concerned with those diseases which are more.or less characteristic of alcoholic poison- ing. The changes and maladies of the digestive organs, such as gastritis with or without jaundice, cirrhosis of the liver, etc., though very commonly the consequence of chronic alcoholism, must be treated separately in other portions of this work, under special sections of pathology and therapeutics. In this some- 400 BOEHM.—POISONS. what restricted department there are consequently only two truly characteristic groups remaining, namely : 1. Delirium tremens, which is essentially the acute form of chronic poisoning by alcohol ; and 2. Chronic alcoholism, properly so called, consisting of a complexity of symptoms of a general diseased state of the ner- vous system, involving both mind and body. Here, too, it must be admitted that even these two groups very often resemble and may be confounded with other forms of disease, so that their right to a separate place in our nosolo- gies may sometimes be very fairly disputed. In the true sense of the terms, the effects of alcohol are no more specific than those of any other poison. II. a. The term " delirium tremens" was first introduced into pathological literature by the English doctor Sutton,1 in the year 1813. This author marked as a special character of delirium tre- mens that, unlike other acute forms of delirium, it was not im- proved, but rather made worse, by bleeding; but on the other hand it could be cured by opium. He lays no stress on alcohol as the pathogenetic agent or prime factor in the disease. This was first specially insisted upon by Rayer in 1819, who proposed the name " oino-mania " for it.2 However, the original name has held its ground, and is now commonly known, not only to the medical profession, but even to the general public. With regard to the true etiology of delirium tremens, two rather opposite opinions have long been held. According to the first view alcohol itself is the immediate cause of the delirium, since it acts as a special irritant or stimulant to the brain and nervous system. This, the so-called toxaemic theory, is almost universally accepted in France and Germany, and is becoming so in England also. The question has been discussed with much AArarmth in that country by such men as Peddie, Anstie, Laycock, Hughes-Bennett, Gairdner, and others. Other observers, who base their view on the proposition that the delirium breaks out 1 A. Fovitte, Du delirium tremens, de la dipsomanie, et de l'alcoolisme. Notice his> torique et bibliographique. Archives generates de medecine. VI. S. Bd. X. 1867. 2 Memoire sur le delirium tremens. Paris. 1819. ANAESTHETICS.—ALCOHOL. 401 first just as the soaker is deprived of his alcohol, contend that the withdrawal of the accustomed stimulus, and thus the with- drawal of the poison, is the true and real cause of the outbreak of delirium (Cuming1). They hold that the nervous system, weakened by the long-continued operation of the alcohol, cannot tolerate the removal of the customary stimulus without suffering a tumultuous disturbance of its equilibrium. And this disturb- ance occurs just as the alcohol is suddenly withdraAvn from the system. According to this view, therefore, delirium tremens is a sort of delirium of inanition. Cuming supports this view by a long series of carefully observed clinical facts, and he does not dispute the possibility of a delirium produced by acute alcoholic poisoning. Other authors, to reconcile these conflicting vieAvs, propose to recognize several varied forms of delirium tremens. Thus, for example, Marston2 recognizes a delirium ebrietatis, which devel- ops itself immediately after a single great excess or debauch, in opposition to a delirium potatorum (of habitual sots). In the first case the alcohol itself, in the latter its withdrawal, would be the proximate causa morbi. Hermann (loc. cit.) has noticed that true delirium tremens more commonly occurs after some great excess at one time, Avhilst long-continued drinking (the so- called "quiet sotting") more commonly induces a condition of chronic alcoholism with paralysis. Sander3 also has noticed cases in which the delirium potatorum seemed to originate in a solitary debauch. It is a matter of old clinical observation that the delirium of sots shows a sort of preference for injuries (such as fractures and dislocations), and for the intercurrent internal diseases of soakers (such as pneumonia). Here the external sur- roundings, for the most part, naturally make a great change in the whole mode of life of the individual who is accustomed to take spirits freely. It is very difficult to hold the balance evenly in such contro- versies. Indeed, it seems probable that both views have some 1 On delirium tremens. Dublin Quart. Journal of Med. Science. No. 98. 1870. p. 62. 2 Edinburgh Medical Journal, Oct. 1860. 3 Archiv fiir Physchiatr. und Nervenkrank. 1868. VOL. XVII.-26 402 BOEIIM.—POISONS. truth, and that both alcohol itself and its [sudden] withdrawal may both be factors in different cases of this disease. But the clinical cases and observations which lie before us do not favor the theory propounded by Marston of varied forms of delirium tremens, according to the cause—since varying causes, in this in- stance, do not seem to produce any variety, or at all events not a corresponding variety, in the symptoms—for delirium tremens is essentially the same under all circumstances. Magnan (loc. cit.) distinguishes the following various degrees of intensity in delirium tremens (delire alcoolique) : 1. Simple delirium tremens (delire alcoolique afebrile). a. Slight form, terminating quickly in recovery. b. More severe form, with more tedious restoration to health, and great tendency to relapses. Particular delusions based on persistent hallucinations are obstinately persisted in. Suicidal tendency. c. Delirium tremens in people with hereditary predisposition to psychosis. G.eat impressionability ; long duration of attacks; imperfect recovery. Very slight . excesses induce slight relapses. 2. Febrile delirium tremens. The outbreak of this disease is always more or less sudden. Well-characterized prodromal or premonitory symptoms are not knoAvn. Occasionally it is preceded by a similar prodromal stage of melancholy, though a shorter one, to that which pre- cedes true attacks of insanity. As a rule, the scene opens with the well-known specific hallucinations of vision common to topers. For the most part they see little dark animals (beetles, rats, birds, serpents, and the like) wherever they turn their eyes. But they are also very often troubled in addition by other hor- rid images, which sometimes assume the form of the devil, some- times of a policeman, or of great black beasts, and the like. Magnan (loc. cit.) considers that the hallucinations of topers are especially characterized by their mobility, as well as by their horrid nature. Delirium tremens is never filled with stiff, fixed visions. In the hallucinations of the sense of hearing, dreadful sounds predominate, although the patients sometimes hear music, and songs, or other pleasant things. Besides all this there are a variety of abnormal sensations, apparently due to anomalies of ANAESTHETICS.—ALCOHOL. 403 the sense of touch and of cutaneous sensibility. The patients will believe that they are enclosed in a fine net of spun glass, or of some textile fabric. All sorts of little insects are crawling under their skin—these sting and torment them—or they have some other delusions of similar kind. At a little later period a peculiar restlessness attacks the voluntary muscles. The patients are continually making little objectless movements with their fingers. Lying in bed, they drum continuously with their fingers on the counterpane, reach out all round them with their hands, as if they would move away some small objects. They have always a very unsteady look—a sort of wild appearance. Sometimes they have even nystagmus. But they seldom entirely lose consciousness, or only for a very brief interval. The patients know where they are and who is with them, and for the most part they answer questions correctly. Very often the last scene in the recent debauch, such as a quarrel, etc., is repeated, some- times half-aloud, sometimes in a noisy delirium ; and sooner or later, along with increased restlessness, there is more or less fierce mania and fury. Delirium tremens differs from mere intoxica- tion in this, amongst other things, that the general deportment and aspect of the patient almost always assumes a character of depression. The delirious patient is worried by his hallucina- tions, and most of his violent acts are done with the object of freeing himself from his tormentors. It is very rare to find the cheerful, hilarious deportment which is characteristic of some forms of mania, and of the earlier stages of intoxication. Cheer- ful delirium is more commonly met with in patients who suffer from pneumonia or some other febrile affection, as well as from delirium tremens. Occasionally we find Avell-marked delusions as to persecution, in which the devil, the police, and similar objects of terror to common men, play the chief part—they imagine that they are being pursued by these objects. It is not uncommon to find the patients inclined to fight those about them, and they are often very mischievous and destructive. These symptoms are usually exacerbated at night, and there is much more dread then than at other times. Complete inability to sleep is also a symptom which is never absent. Another somatic symptom is the tremor, 404 BOEHM.—POISONS. which varies both in extent and intensity, and may even be absent altogether. The face is generally flushed, the conjunctiva injected, and the patient usually perspires very freely. The patient looks very feverish. It is easy to understand that accurate thermometrical observations are not easy to take under such circumstances, and we have, therefore, no very reliable information on this point. The duration of delirium tremens is limited to a few days in the great majority of cases—at the most it extends to a fortnight, whilst the disease is at its height. There is delirium even in the daytime, it grows worse Avhen twilight begins, and is most severe at night. On the other hand, when convalescence commences, one of the first signs of improvement is freedom from delusions during daylight. During the evening hours and in the night the patient is still more or less troubled with a return of the hal- lucinations, until at length, after he has enjoj^ed tranquil sleep for a few nights, he may be regarded as quite cured. If there are surgical complications, or some internal malady complicate the case, the course of the disease is often very unfa- vorable, and death may occur as early as in the first week, with all the symptoms of asthenia. Every practical surgeon knows, from his own experience, that the prognosis of cases of pneumo- nia or fractures, complicated with delirium tremens, is a very unfavorable one. Magnan, in his recent work on Alcoholism, in addition to the ordinary form of delirium tremens Avhich we have just described, mentions a severe febrile form which very commonly runs a fatal course in a very few days. The fever in such cases, according to Magnan, is not so much dependent upon any internal or external complications or symptoms, but must be regarded as idiopathic. Up to the present time he has published seven cases of this kind, which were remarkable, not only for the high fever (tem- perature of 42° C. = 107.6° F.), but also for the very severe tremors which extended all over the body, and continued even in sleep. These tremors could be plainly felt by the hand in almost every region of the body. Besides this, the " febrile de- lirium " is characterized by extreme muscular weakness, and the pulse, which is slow at first, becomes much quickened later on, ANAESTHETICS. —ALCOHOL. 405 and is extremely weak. Sometimes there is albuminuria, Fi- nally death occurs, with sjmiptoms of extreme general asthenia. The special etiology of this form is as yet unknown. Yet it is known to follow repeated and recent excesses (unlike the deliri- um tremens which follows accidents or intercurrent diseases—the so-called traumatic delirium of many authors). It is not possible to describe here in detail all the modifica- tions of symptoms met with in different cases of delirium tre- mens, which deviate in different ways from the sketch just presented to the reader. It should, however, be noted that tetanic and eclamptiform convulsions have been observed in some cases. It is very rarely that we find a man attacked only once by this complaint, unless, indeed, the first attack has proved fatal. It is far more common to see the same patient come again and again to the hospital, at longer or shorter intervals. The dele- terious effects of alcohol on the nutrition of the tissues cause the intervals between the attacks to become shorter and shorter in most cases, because the patient after each attack has a lessened store of bodily and mental power to sustain him. So, unless death speedily closes the scene, the patient gradually settles down into the ranks of the demented and paralyzed, and sooner or later succumbs to marasmus. In the bodies of such patients we find signs of varied and severe chronic diseases of the stomach, pigmented and thickened mucous membranes, the liver most frequently in a state of fatty degeneration, and the kidneys are sometimes in a similar state. Pachymeningitis is also a common condition, especially when several attacks of delirium tremens have occurred. The pia mater is found more than normally adherent to the superficial cortical layers of the brain, and the brain itself is described by several observers as more than usually dry and anaemic. II. b. It is far more difficult to describe within a moderate compass the varied forms of "chronic alcoholism," properly so- called. It is without exception the consequence of long-con- tinned and continuous abuse of spirits, through which the body is gradually and systematically accustomed to larger and larger quantities of the poison ; and the whole system, down to its very 406 BOEHM.—POISONS. foundations, is shattered and shaken. Those who belong to this category are very seldom seen in a state of actual drunken- ness in the later periods of their wasted lives—in fact, at those periods which concern us at present. They follow their busi- nesses or professions, or exercise their trades with a constantly and rapidly diminishing remnant of their physical and moral powers, and are compelled to sustain these extremely tottering bodily powers by constantly increasing quantities of alcohol. Some of these habitual sots are attacked by and succumb to diseases of a casual kind, which present no symptoms charac- teristic of chronic alcoholism. We need not therefore concern ourselves with these. But other habitual soakers suffer from symptoms which cannot be clearly identified with any of the known and recognized diseases in our nosologies. In the first place we must mention a number of psychical disorders, which are, if we may say so, specially characterized by their want of character or want of individuality—reminding us of the "moral insanity" which has lately given rise to so much discussion. In such cases we really do not know if the craving for drink, the alcohol mania, be the original cause of the malady, or whether we must regard the craving as itself one of the symptoms ; unless, indeed, Ave have watched the develop- ment of the disease from its very beginning. Continual struggles with temptation, and continual yieldings to it, reduce the man who was, perhaps, at first a well-meaning person, to a state of irreconcilable conflict and dissension with himself, with duty, and with the world around him. Although at first their intellectual powers are as strong as ever, such persons suffer severely from great anomalies of the passions and affections, and from a condi- tion of deep melancholy, which is often associated with a ten- dency to kill themselves; and they strive to rid themselves of these feelings by a continual resort to their one remedy of fresh indulgences in alcohol. Their power of resistance grows gradually weaker and weaker, whilst at the same time, step by step, their intellectual and physical powers grow more and more feeble. The man is now capable of committing crimes in order to satisfy the craving which is now his one ruling passion. In this category one often ANESTHETICS.—ALCOHOL. 407 finds men of position and eminence—high-class men in every sense. And just in proportion to the original development of what we may call the higher ethics, is the psychical conflict in- creased, and is the completeness of the moral ruin. Sots of the lower orders do not fall so Ioav, because they have never climbed so high. In the few moments when the man is free to think, the very consciousness that he has ruined not only himself, but his family, becomes itself a fresh factor in the generation of fresh mental disorders, and assists the action of the original agent of mischief, the alcohol. The further course of cases of this kind is by no means uniform ; very many, indeed, put an end to their own lives. Comparatively few are reclaimed in the long run. The great majority, indeed, perish by intercurrent diseases, or are attacked by general paralysis; or some one of the psychical anomalies from which they suffer develops into a dementia which is strongly tinctured with gloom. A large number of the cases of so called dipsomania un- questionably belong to the class of cases which has just been described. Salvatori and Bruhlkramer,2 who first accurately described this form of insanity, and others of the earlier writers on the subject, referred the whole of the symptoms, including the craving for drink, to the abuse of alcoholic beverages. In later times, however, especially since Esquirol, writers on mental diseases admit that there may be other causes which bring about this condition and this craving, without excesses in drink hav- ing necessarily been indulged in previously—such causes, for example, as hereditary predisposition, grief and privations, loss of property, and the like. There are, however, many points, even in such cases, of resemblance to those before described, especially as regards their first beginnings. AH who have written on this subject agree in regarding a sort of cyclical course to be one of the pathognomonic signs of the disease. Dipsomania occurs in the form of a repeat- edly recurring rage for drinking, which, according to the de- scriptions of the older writers, is preceded by very pregnant prodromal symptoms, particularly unpleasant sensations in the 1 For the history and bibliography of this subject, see Fovi/le, loc. cit. 408 BOEHM.—POISONS. lower part of the abdomen, nausea, vomiting, want of appetite, and general depression. It is these premonitory symptoms which act as the proximal causes which drive the man to drink, which he continues to excess for a longer or shorter space of time, until either an attack of common insanity (Raserei) or general depression, combined with disgust at all spirituous liquors, puts an end to it for the time. In all these cases the sotting itself is the leading pathological symptom. In their further destiny these cases perfectly agree with the other forms of chronic alcoholism. This is not the place for any discussion of the question, whether dipsomania should be considered as a characteristic disease in itself. There is a great discrepancy of opinion in the literature of the subject. In the article by Cum- ing, quoted before, undoubted cases of dipsomania (periodic rage for drinking) are described as preceding all attacks of the com- mon form of delirium tremens. Even Griesinger' remarks that this condition very often terminates in an attack of madness. As regards the etiology it must be owned that the number of cases in which there have been no previous excesses in Baccho is very limited." The closing scenes in the course of chronic alcoholism are so varied, that it is difficult to present a general picture of the whole disease. However possible or profitable it may seem to be to pick out a number of identical or similar cases for clinical observation, and thus to construct typical forms or groups of cases of chronic alcoholism, yet such a systematic semeiology does not seem justified in a scientific point of view, and may even prove dangerous, by seeming to support views which may after all be erroneous. In truth, there is little order or constancy in the grouping of the various symptoms. They may be mingled together in the strangest combinations, thus producing mixed forms, which would certainly lead any one who looked upon them as pathological entities, or as accurate typical forms of disease, into sad mistakes. Unfortunately, as regards chronic alcohol- ism, we have not yet a sufficiently firm foundation of anatomical 1 Die psychischen Krankheiten. Stuttgart. 1861. 2 See also C. With, Ueber Dipsomanie Dissert. Berlin. 1869. ANESTHETICS.—ALCOHOL. 409 and pathological facts whereon to rear a systematic edifice. In order to get some direct ideas from this chaotic mass, it is very desirable, for the present, to sever as far as possible the psychical from the somatic or corporeal disorders. The psychical bear the general stamp of imbecility, and of persistent and general psychi- cal decay, which manifests itself in various ways, and more or less actively. The general psychical degeneration extends to the intellectual powers as well as to the character of the patient. Both intelligence and character are stamped with feebleness, and this exhibits numerous gradations doAvn to the absolute psychi- cal nullity of apathetic dementia. This great variety in the behavior of the patients is to a great extent dependent upon the number and character of the delusions from which they suffer, and the erroneous notions which are founded on these by a large number of those suffering from chronic alcoholism. These, com- bined with the remains of the emotions or affections, the amount of which differs greatly in different patients, produce varied and anomalous forms or conditions of insanity: sometimes forms of exaltation with changing and absurd delusions, sometimes melancholic forms with religious mania, delusions of persecu- tion, and the like, and sometimes mere tranquil dementia. It is not very uncommon for the steady downward course of this disease to be temporarily interrupted by maniacal exacerbations, which occur also in other mental diseases not caused by the abuse of alcohol. Such patients as we have now endeavored to describe are, as a rule, free from any very severe bodily or somatic ailments, and they form a large contingent in the popula- tion of our asylums. As might be naturally supposed, they are all perfectly incurable and hopeless cases. Another class,1 scarcely less numerous, is made up of those who suffer from various symptoms of the so-called general neuroses. A large number of these are included in the class of general paralytics. Here, in addition to the psychical symptoms characteristic of this condition (psychosis), we have different degrees of paral- ysis of motion and sensation. Paralytic dementia is one of the commoner terminal diseases of chronic alcoholism. We need not stop to describe this condition, since the symptoms are but little affected by the etiology. And besides these, apoplectic and epi- 410 BOEIIM. —POISONS. leptic attacks may occur (intercurrently) in the course of chronic alcoholism. The apoplectic seizures are manifestly the basis of the " hemiansesthetic form" of chronic alcoholism, which Mag- nan (loc. cit.) describes from observation of ten parallel cases of the kind. The characters of this form are as follows: More or less complete loss of sensation (anaesthesia) of one-half of the body occurs in the course of chronic alcoholism in consequence of a more or less typical apoplectic seizure ; sometimes this may be preceded by slight premonitory symptoms, such as headache, tingling sensations (formication), and giddiness. This loss of sensation is not confined to the skin merely. The mucous membranes (ocular and palpebral conjunctivae, that of the nos- trils, mouth, urethra, and anus) are also affected, so are the organs of sense (amblyopia and amaurosis); and deep-lying tis- sues, such as the muscles, are also affected. Paralysis (of motion) is at the same time more or less clearly pronounced; and may even improve, whilst the lost or impaired sensibility remains as before. The temperature of the affected side is often diminished by 2° to 3° Centigrade (=3.6° to 5.4° F.). Magnan believes that these symptoms depend upon central disease (Herderkrankung) in the neighborhood of the thalamus opticus, of the corona radiata, and of the lenticular nucleus (of the corpus striatum); but apart from this we may have in the course of chronic alcoholism, in combination with any of the psychical symptoms named above, partial paralyses, anaesthe- sias, hyperaesthesias, cramps, and convulsions in various parts of the body. Of all the organs of sense, the eye is the most frequently attacked. Galezowskil generally found well-developed dyschromatopsia in alcoholic patients. Of yellowish-green and bluish-green they could only distinguish the green; they confounded violet with red, and brown with gray. Magnan (loc. cit.) has repeatedly observed the same. Besides this, amblyopia and amaurosis occur in various degrees. Daguenet" investigated these condi- tions still more carefully. He found atrophy of the optic nerve 1 Paris. 1868. Reference in Schmidt's Jahrb. " Annal. d'oculist. 1869. LXII. Reference in Schmidt's Jahrb. 1869. ANESTHETICS.—ALCOHOL. 411 in many cases of disordered vision. The sudden commencement of weakened sight appeared very remarkable to him; every- thing round the patient seemed in a mist, so that even persons ten paces off could not be recognized, and so on. The patients saw better on dull days than on bright ones. They could not be trusted as to colors. The tint of well-known people seemed altered to them ; sometimes they confounded gold coins with silver ones. There were very few objective symptoms with all this. The rather dilated pupils acted badly. At the beginning the ophthalmoscope only revealed a slight infiltration round the optic papilla, later on actual atrophy of the optic nerves. Besides all these various disturbances of the nervous system, and all this disorder of the inner life of the man, it is very com- mon to find the general nutrition of the body much altered by chronic alcoholism. No doubt, the chief cause of this is to be referred to the changes in the digestive organs—the chronic gas- tric catarrh alone being quite sufficient to prevent a proper and regular quantity of nourishment being taken, and making diges- tion, in the true sense of the term, almost an impossibility. But the dissolute mode of life of the patients and the psychical dis- orders themselves must also share the blame, and partly explain the gradual decay and diminution of the bodily powers and the great amount of emaciation usually present. It has been remarked already that many forms of disease, morbus Brightii, cirrhosis of the liver, and the like, may develop themselves in alcoholic patients, and thus help to bring about a fatal termina- tion. Surmay' describes several cases of chronic alcoholism in which the patients died with symptoms of uraemia, but without albumen in the urine. But there do not seem to have been any very extraordinary symptoms ; and as there were no post-mor- tem examinations, there seem to be no special reasons for mak- ing a new type of chronic alcoholism, under the name of the '•uraemic form." A few remarks must be made on the sexual functions in habitual drunkards, and on the influence of alcohol on genera- tion. In the earlier stages, as a rule, the sexual functions are 1 De quelques formes peu connues de la cachexie alcoolique, etc. L'Union Medi- cale. 19, 21. 1868. 412 BOEHM.—POISONS. very little altered, if at all, and it is only in the later stages that sterility attacks both sexes. It seems impossible to doubt any longer that the children of alcoholic parents not only exhibit, for the most part, a very great predisposition to psychical disorders, but that they also generally inherit a very badly-constituted ner- vous system. Indeed, it is asserted in books that children begot- ten in a state of drunkenness are epileptics from their very birth. Alcoholism in the father is worse as regards the offspring than alcoholism in the mother (Bruhl-Kramer). The results of recent researches into the specific effects of the liqueur called absinthe are very closely related to the varied symptomatology of alcoholic poisoning. This liqueur is gener- ally admitted to be more used in France than anywhere else. Besides alcohol, it contains several ethereal oils (anise, fennel, etc.), of which the most important is the oil of Avormwood. It has been over and over again observed in France that the dis- orders from which absinthe drinkers suffer differ from the cus- tomary forms of alcoholism by the frequency of well-marked epileptiform convulsions. Then Magnanl made experiments on animals with the different constituents of the absinthe liqueur, and found that moderate doses of oil of wormwood were suffi- cient to bring about paroxysmally occurring tetanic convulsions in dogs and other warm-blooded animals. Neither alcohol alone nor the other constituents of absinthe would do this in similar doses. Alcoholic mixtures containing the oil of Avormwood pro- duced the characteristic effects of alcohol in dogs, and a little later the specific effects of the wormAvood. The anatomical changes, in other words, the morbid anatomy of cases of chronic alcoholism is almost as protean and incon- stant as the forms under which the disease occurs. We may find the most varied degenerations and atrophic conditions; and it is almost impossible to include all of them in this slight sketch. Of all the organs which are most commonly found dis- eased in the bodies of alcoholic patients, the mucous membrane of the gastro-intestinal tract takes the first place. There the ' Loc. cit. See also CMlland, Etude experiment, et chimique sur l'absynthisme et l'alcoolisme. Paris. 1871. ANESTHETICS.—ALCOHOL. 413 various stages and sequelae of chronic catarrh may be found, as has already been intimated. According to Lancereaux1 the thickening of the mucous membrane occurs especially in the stomach and caecum; and is doubtless due to an overgrowth of connective tissue. On the mucous membrane of the stomach we find patches of hyperaemic vessels, sometimes flat (superficial) erosions, and very commonly indeed, a great increase in pigmentation. We do not know of any accurate microscopical researches on the changes in the glands of these organs. No changes are to be met with in the organs of respiration which are specially characteristic of chronic alcoholic poisoning. The large glands of the abdomen are far more frequently the seat of very extensive tissue-changes. The liver is sometimes found only exhibiting fatty degeneration, sometimes in the gran- ulated condition due to interstitial development of increased connective tissue, which is, in fact, cirrhosis of the liver. The kidneys, though not quite so often, are affected in the same way. As regards the nervous system and its envelopes (mem- branes), pachymeningitis haemorrhagica plays so important a part, that it has been considered by many as pathognomonic of chronic alcoholism. According to Kreminansky (loc. cit.) and Neumann (loc. cit.) these changes can be induced experimentally by giving dogs alcohol for a long time, mixed with their food. The brain is sometimes attacked with a peculiar dry and tough condition, in which the cortical substance of the convolutions is smaller than usual (wasted), and the ganglionic cells have under- gone fatty degeneration (Wilks4). Fatty degeneration of the voluntary muscles and the same disease of the heart, and thick- ening of the coats of the veins (pylephlebitis potatorum) till their calibre is almost obstructed, are very common conditions according to Lancereaux. The treatment of the different stages of alcoholic poisoning has given rise to a great deal of contro- versy and difference of opinion. In the acute form of alcoholic poisoning the stomach-pump has lately been used with very 1 Gazette hebdom. 186j. 2 Journal of Med. Sciences. 1864. 414 BOEHM.—POISONS. good effect in order to remove the alcohol which remains in the stomach, often in large amounts. But for the rest, it may easily be understood that the chief part of the treatment must be purely according to the symptoms, since we possess no medi cine which can act as a direct antidote to alcohol, or neutralize at once its pernicious effects. The local and general abstraction of blood, though formerly recommended, has very properly been generally abandoned. When coma threatens, and respiration is defective, cutaneous irritants (frictions, cold applications, mus- tard poultices, etc.), and under some circumstances artificial respiration, are indicated. Treatment by pouring in drugs, we believe to be superfluous and useless. The therapeutics of delirium tremens, of late years, has chiefly consisted in the free use of opium in some cases, of the use of chloral in others, or the use of moderate quantities of alcohol—those authors who attribute the outbreak of delirium tremens chiefly to the sudden withdrawal of the alcohol express themselves most warmly as to the good effects of the treatment by alcohol (see Cuming, loc. cit.). Digitalis and the oxide of zinc have also been much recommended. It cannot, however, be denied that many cases of delirium tremens do very well with- out any special medication if the patients are carefully watched and nursed for a few days. Such treatment is indeed to be very highly commended in those cases where the general bodily con- dition of the patients is not such as to cause anxiety, and when the case is not complicated by any acute disease. The tolerance of those afflicted with this delirium for even enormous doses of opium is a well-recognized fact; and the opium treatment of the disease is one of the most Avidely-diffused methods. In estimat- ing its success, it must not, however, be forgotten that in very many cases it seems to have no effect whatever on the progress and course of the disease. In those patients who are much reduced, and whose hearts show but little power, we consider the use of large doses of opium to be counterindicated. The points of view which appear to necessitate the use of narcotics coincide in this, that they aim at combating and overcoming the excitement and the sleeplessness. It seems, however, not to make very great difference whether opium, chloral, or some other ANESTHETICS.—ALCOHOL. 415 hypnotic be used for this purpose, if due regard be paid to the special points in the case and the constitution of the patient. An attempt to set up a model is just as objectionable here as any- where else ; and we do not think it by any means desirable to lay down as a canon that all cases of delirium tremens should be treated by large doses of opium. The recommendations of digi- talis in delirium tremens, which have generally come from Eng- land or Sweden, have been based upon the most diametrically opposite views of the pathology of the disease and of the mode in which the drug acts. Fothergill' has very recently recom- mended digitalis, more particularly in those cases of delirium tremens in Avhich the pulse is small and irregular and the pro- pulsive poAver of the heart is Aveakened. But the ordinary con- dition of the digestive organs of tipplers is the chief objection to the general use of digitalis. Waring-Curan2 has recommended oxide of zinc, in pills, as a ionic after-treatment. This ought never to be taken on an empty stomach. Those who have taken the zinc for a long time are said not to suffer from delirium tre- mens again, even if they return to excessive drinking. Marcet3 has also observed good results from this remedy in cases of chronic alcoholism, and cured ten cases out of twenty-seven with it. Hermann (loc. cit.) says the acetate of zinc is the next best remedy to opium. But the general experience of the use of this remedy is not yet sufficiently large to enable us to give a decided opinion on its merits. The same may be said of the treatment by alcohol. It is very likely that many cases would do better by a more gradual withdrawal of the alcohol, or by allowing a little to be taken all through. Of the other remedies which have been proposed for delirium tremens, we may mention capsicum, Avhich Hermann has several times used successfully when other means failed ; also camphor and sumbul-root, which sometimes prove very useful to old topers; lastly, tartar emetic in large doses. Far more important than any, or all, of these remedies is the dietetic treatment of the patients, who, especially when the disease lasts long, require the diet to be carefully studied 1 Brit. Med. Journal. 1871. 'Lancet. 1868. 3 Med. Times and Gazette. 1859. 416 BOEHM.—POISONS. and adapted to their case, in order that they may recruit their strength. The treatment of cases complicated by acute dis- eases'5 belongs to the special departments of Pathology and Therapeutics. The treatment of chronic alcoholism generally proves a fail- ure, since we can seldom perfectly succeed in following the causal indication. In other words, we can seldom wean the patient from alcohol at a sufficiently early stage. Here, too, the proper nourishment of the patients is a subject of the greatest importance. We may say the same of the careful treatment of the stomach diseases from which they suffer. Nor is a moral regime suitable to the individual patient of less importance. Drugs are of less value here than in delirium tremens. We therefore refrain from filling our pages with a long catalogue of remedies. CHAPTER II. POISONING BY CHLOROFORM. It is scarcely possible to find any other substance except chlo- roform which combines, within so narrow a compass, properties at once so salutary and so deadly, as regards its action on the human body—properties, too, which, although exactly contrary, pass, by almost imperceptible gradations, one into the other. On this account, ever since Simpson introduced it into surgical prac- tice in 1847, its action as a poison has engaged almost as much general attention as its therapeutic uses. And although it has again and again conquered in the now almost annual contest Avith new candidates for favor as anaesthetics, this very pre-emi- nence is doubtless due, in great part, to the diligent study which has been given to its dark side, and the precautionary measures these have suggested. Chloroform (OHCl3) is a very mobile colorless fluid, of greater density than water, not miscible with that liquid, and very vola- tile. When evaporated it should leave a peculiar but pleasant smell behind it, which some people characterize as "sweet," on account of the impression simultaneously made by the vapor ANESTHETICS.—CHLOROFORM. 417 on the nerves of taste in the mouth, the sensations of smell and taste being curiously blended. Its physical properties render chloroform just as adapted to diffuse itself through the circula- tion, along with the inspired air, as it is unsuited for introduc- tion into the stomach (by itself); for its sudden evaporation, and perhaps immediate action on the nerves of sensation, as a strong irritant to all mucous membranes, do not permit of large doses being introduced into the stomach for medicinal purposes. No doubt, however, some of the vapor gets into the blood, even when swallowed. Chloroform acts in a similar manner upon the skin, although its irritant action is less marked. It may pass into the blood through this channel also, provided the necessary external conditions are complied with (hindering its evaporation into the atmosphere, etc., etc.). This is rendered still more easy by the property chloroform has of easily dissolving the fatty matters which coat the epidermis of all parts of the surface, except perhaps the palms of the hands and soles of the feet—a property not shared by watery solutions. Parisot * has shown by experiment that when, for example, a solution of atropine in chloroform is applied to the skin, it is much more quickly absorbed than an alcoholic solution applied in a similar manner, its action being tested by the production of mydriasis. The greater part of the chloroform is eliminated in the air breathed out of the lungs—that is, in expiration. But Perrin, Lallemand, and Duroy (loc. cit.) have found chloroform vapor in the cutaneous secretions of persons chloroformed, although they could not detect it in the urine. Views and hypotheses founded upon d priori reasoning, on the well-known physical and chemical properties of this agent, have led to numerous mistakes as to its behavior in relation to the blood, and many errors had to be abandoned when they were put to the test of experiment. For example, B. Clemenz thought that the rapidly fatal action of chloroform was due to its not containing any oxygen, because we cannot conceive of life with- 1 Sur le role de l'epiderme en presence de l'eau, du chloroforme, et de Tether. Acad, des sciences. Seance du 17. VIII. 1863. Gazette des hopitaux. 1863. No. 99. p. 396. VOL. XVII.—27 418 BOEHM.—POISONS. out oxygen. Others thought that chloroform sometimes rapidly abstracted oxygen from the blood, or decomposed it into prussic acid and sal ammoniac, etc. A more detailed account of these erroneous views may be found in the article by Schmicdc- berg.1 But it was very soon established by the experiments of A. Boettcher (and, it Avould appear, simultaneously by Sansom2) that under certain conditions the blood of various animals is acted upon by chloroform in such a way that the blood-corpuscles are dissolved, and the haemoglobin crystallizes out. In human blood chloroform produces the same solution, but no formation of crystals. Schmiedeberg (loc. cit.) shows that it is highly probable that chloroform enters into chemical combination with the substance of the red blood-discs. For when defibrinated blood and chloro- form are mixed together, outside of the body, there is produced a peculiar albuminous precipitate, of the color of red sealing-wax (chloroform coagulum), the chemical constitution of which shows a considerably greater percentage of chlorine than normal blood exhibits. On the other hand, the serum of the blood, mixed with chloroform, contains almost as much chlorine as normal serum. It would therefore appear that in this chloro- form coagulum, from which very little chloroform can be recov- ered by simple distillation, this substance has entered into some peculiar combination with the blood-corpuscles, the exact nature of which we do not yet know. In the meanwhile the fluid por- tions appear not to contain any chloroform. It is a matter of great interest to note that in forming this compound chloroform loses its own peculiar and striking physical properties, so that, in medico-legal investigations on the presence of chloroform in the blood, it can never be recovered from that fluid except in extremely small (minimal) quantities. Bonwetsch (loc. cit.) has also shown by his experiments that chloroform, like alcohol and ether, retards tissue-changes in the 1 Ueber die quantitative Be=timmung des Chloroforms im Blute und sein Verhalten gegen dasselbe. Archiv fur physiologische Heilkunde. VIII. 1867. 2 Ueber Blutkrystalle. Eine physiologisch chemische Abhandlung. Dorpat. 1862. Ueber die Wirkung des Chloroforms auf das Blut. Virchow's Archiv. XXXII. 1867. Chloroform, its Action and Administration. By A. E. Sansom. London. 1865. ANESTHETICS.—CHLOROFORM. 419 blood. Blood mixed with chloroform gives up its oxygen (oxy- hemoglobin) to reducing agents far more slowly than normal blood. Unfortunately, none of these facts are fully applicable to the living human body, since they all relate to blood drawn from the veins. No one has yet observed the blood-corpuscles, dissolved in blood, still circulating.' Schmiedeberg (loc. cit.) thinks that it is very probable that the combination of chloroform with the blood-corpuscles which he has noted does not occur in the blood which circulates through a living animal, since the combination which occurs outside the body is again broken up by exposure to the oxygen of the at- mosphere. The constant presence of oxygen in the circulating blood, therefore, renders it unlikely that any such compound can be formed in life. The conclusions drawn by Sansom" from the behavior of chloroform with blood are at least not to be implicitl}r relied on, since he does not hesitate to attribute the whole of the effects of chloroform to this solution of the corpus- cles. We are still a long way off from a perfect knowledge of the effects of chloroform. Yet the facts just mentioned are valu- able as furnishing us with hints (finger-posts) as to the direction our inquiries should take if we hope to succeed. That solution of the blood-corpuscles cannot well be the primary cause of the effects of chloroform would appear, amongst other reasons, from the fact furnished us by Hermann (loc. cit.), that even those mem- bers of the animal kingdom which have colorless blood are af- fected by chloroform. Some time since this observer laid espe- cial stress on the effects of chloroform upon protagon, effects which he himself had demonstrated. These are common to all 1 L. Hermann (Ueber die Wirkungsweise einer Gruppe von Giften. Archiv fiir Anatomie, Physiologie, etc 1866) remarks that a sure test of the occurrence of dissolu- tion of blood-corpuscles is afforded by the presence of bile-pigments in the urine, and eventually by jaundice. We do not know of any further observations in this direction. Jaundice is sometimes met with as a consequence of chloroform narcosis, in accordance with Hermann's views. 2 Loc. cit. p. 62. Narcotism (or, to speak more particularly, chloroform narcotism^ is due not to a special poison which " mounts to the brain," but to the influence of an altered blood. "Narcotism is suspended oxygenation." (!) 420 BOEHM.—POISONS. the volatile anaesthetics. Protagon is the substance which 0. Liebreich is admitted to have first discovered in the brain-sub- stance. Volatile anaesthetics dissolve protagon, and this solution may probably be the basis of their anaesthetic operations, accord- ing to L. Hermann. It is quite out of the question for us to discuss here the question of the existence of protagon, or of its relations to lecithin. Under any circumstances we may pretty safely admit that these agents are solvents for those constituents of the nerve-substance which contain phosphorus. But alas ! we are ignorant as to the part played by such substances in the vital actions of the nervous organs. Hermann's hypothesis is, therefore, as he himself admits, by no means one that fully ex- plains the phenomena. But it is one of the best representatives of that class of theories which seeks to explain the operation of chloroform, not by any altered constitution or properties of the blood, but by a direct action upon the nervous organs. In the absence of fully explanatory facts, it is open to us to choose whichever of these theories Ave like, although we certainly be- lieve that the opinion of a direct action upon the nerves is the most probable one. The essential symptoms produced by chloroform are the expression of functional disturbances of the central organs of the nervous s}Tstem. A short-lived exaltation of the activity of these organs is succeeded by a more or less perfect suspension of this activity; a suspension which, in extreme cases, extends to those centres of the vegetative functions of the organism (respiration and the action of the heart) which are usually not attacked. It is no doubt due to its physical properties that chloroform has the peculiar poAver of producing its narcotic effects, one after the other, in a far briefer space of time than is the case with most other narcotics. As quickly as it is received into the blood, and is again eliminated from it, so suddenly do its effects appear and disappear again. It has just been remarked that the action of chloroform is by no means limited in all cases to the organs which regulate the animal functions of life. And since this encroachment on the most important vital processes, those of respiration and the movements of the heart, are the special and almost only dangers of chloroform, it has for a long while been ANESTHETICS.—CHLOROFORM. 421 the earnest endeavor of medical men to discover accurately the real causes which underlie these unwelcome properties. To this we owe a long series of careful experiments upon animals, Avhich have been made with the object of discovering the causes of the toxic action of chloroform. Scheinesson * has explained the action of this poison on the circulation by means of experiments on animals. The movements of the heart become weaker, and the lateral pressure in the arterial system is lessened not only on this account, but because the vaso-motor centre in the spinal cord (or medulla oblongata) loses its irritability through the poison, and may even be perfectly paralyzed. The weakening of the activity of the heart does not depend upon any influence from the nerve-centres, but is dependent rather on a direct alteration of the motorial power of the heart, which may be con- sidered by some as due to a weakening of the automatic centres for movement in the heart itself (ganglia of the heart), or on direct weakening of the muscular fibres of the heart. These changes in the circulation are, it would seem from Scheinesson's experiments, also the cause of the decrease in the bodily temper- ature, and of the retardation of tissue changes in chloroformed animals. The results of the English Chloroform Committee's experiments perfectly agree with those of Scheinesson.8 In these, also, decrease of arterial pressure was observed as a constant effect of chloroform. Lenz's3 experiments with the haemo- dromometer, in which the swiftness of the blood-current in the carotid artery sank to one-seventh of its normal value, also speak strongly of the diminished propulsive power of the heart from chloroform. Vierordt, however, established a far less considerable diminution of the rapidity of the circulation—amounting to about four-fifths of the normal rate. Brunner and Gall4 have also made experiments upon the blood-pressure. If we are thus able to refer the deaths from chloroform, in a large number of the cases, to the paralyzing effects of this agent 1 Untersuchungen liber den Einfluss des Chloroforms auf die Warmeverhaltnisse des thierischen Organismus und den Kreislauf. Dissert. Dorpat. 1868. - Report of the Committee appointed by the Royal Medical and Chirurgical Society, etc., etc. Med. Chirurgical Transactions. Vol. XLVII. 1864. pp. 323—412. 3 Dissertat. Dorpat. 1853. 4 Compare Scheinesson, 1. c. p. 68. 422 BOEHM.—POISONS. upon the heart, it is no less true that there are yet other observa- tions which make it more than probable that the fatal termina- tion is sometimes brought about by paralysis of the respiratory centres. Numerous experiments in this direction were instituted by the London Chloro- form Committee. A difference was at once noticeable, according as concentrated or dilute vapors were inhaled. The duration of life of the animals (dogs) was almost directly proportional to the concentration of the vapor. The concentra- tions (or as we should call them, dilutions) used were (1) weaker, of air containing from 1 to 15 per cent, of chloroform; (2) stronger, with at least 40 per cent, of chloroform in the air. In the weaker compound, the intensity and quality of the symptoms produced were not much affected by the mode of breathing, whether through mouth or nose, or through an opening in the trachea. But when the strong concentrated vapors were used, through either mouth or nose, almost immediate slowing of the pulse (after 80 seconds), and respiration (after 105 seconds) occurred, and somewhat later, stoppage of the heart, in about five minutes. But if the con- centrated vapors were inhaled through an opening in the trachea, the heart stopped before respiration ceased. The pulse always vanished a little before the move- ments of the heart ceased. Concentrated vapors often caused an immediate, though somewhat brief, stoppage of respiration. This was absent when a mixture of 6 per cent, of chloroform in air was employed. This was always followed by increased frequency of breathing, at first with greater, afterwards with less depth of the separate inspirations, which gradually decreased to nothing. When diluted vapors were used, the respirations often sank to nothing, and then began again afresh after from twenty to forty seconds. The fresh application of chloroform stopped them again. Section of the vagus nerve in chloroformed dogs had less effect than it has on dogs not under chloroform. Chloroforming after section of the vagus nerve diminishes the consequences of this operation (increase of the frequency of the pulse and dyspnoea). We must pass over a number of theories and experiments on the action of chloroform,1 but we cannot refrain from alluding to one very important point as regards the true nature of chloro- form narcosis. Some authors have considered the primary cause of the occurrence of certain symptoms affecting respiration and circulation to be a reflex irritation of the centres concerned. 1 Consult on this Kohler, Die neueren Arbeiten iiber die Anaesthetica. Schmidt's Jahrbiicher. Bd. CXLII. p. 209, CXLV. p. 305, and CLI. p. 193. ANAESTHETICS.—CHLOROFORM. 423 Dogiell and Holmgren2 considered the stoppage of the heart and the disturbed respiration, which they both noted as common in animals in the first stage of the action of chloroform, as the result of a previous reflex irritation of the vagus .centre in the medulla oblongata, through one of the sensory nerves of the nose, or of the naso-laryngeal mucous membrane. Holmgren (loc. cit.) has shown, however, that only those branches of the trigeminus are affected which ramify in the naso-laryngeal mucous membrane. The phenomena in question are weakened after section of the superior laryngeal nerves, and are altogether absent after cutting through the trigeminal nerves, as Avell as the vagus in the neck. These disorders are not produced in the first stage of the inhala- tion if the chloroform be inhaled through a tracheal fistula (thus avoiding the above-named portions of the mucous membrane). Lastly, we must notice a view lately advocated by A. W. Smith.3 This author considers that a very common cause of the stoppage of breathing in chloroform narcosis is to be found in the paresis (anaesthesia) of the termination of the sensory nerves in the lungs, induced by chloroform—these nerve-endings being concerned, in the normal state, Avith the regular performance of the respiratory movements. We cannot deny that there is some foundation for this theory, when we recall to mind the results of Breuer's4 experiments on the part played by the peripheral ter- minations of the vagus nerves in the act of respiration. Accord- ing to Breuer, each inspiration causes an irritation of the sensory terminations of the vagus nerve by the very act of expansion of the lungs. It is carried by the centripetal vagus fibres to the centre for expiration, and an expiratory movement is at once set up. By a similar mechanism an inspiration is made to follow an expira- tion, so that in a certain sense the movements of respiration are automatic and self-regulating. As the cooperation of the vagus 1 Ueber die Wirkung des Chloroforms auf den Organismus der Thiere. Archiv fiir Anatomie und Physiologie, etc. 1866. 2 Virchow und Hirsch, Jahresbericht, etc. 1867. .Referat von Th. Husemann. 3 One of the Causes of Death from Chloroform. American Journal of Medical Sciences. 1871. 4 Die Selbststeuerung der Athmung durch den Nervus vagus. Sitzungs-Bericht der Kaiserlichen Akademie zu Wien. Mathem. -physik. CI. Bd. LVHL 424 BOEHM.—POISONS. nerve plays a leading part in the whole of this mechanism, it is quite conceivable that the sudden paralysis of the sensibility of the lungs, especially when the central organs of respiration are simultaneously affected, must greatly contribute towards the stoppage of respiration. Richardson l believes that death from chloroform is brought about in many different ways, by func- tional disturbances of the various parts of the nerves belong- ing to or regulating the heart. We think, however, that his views are not much supported by fact, and are somewhat too dogmatic in tone. From the foregoing statements it is quite evident that our knowledge of the real nature of the action of chloroform is by no means sufficient to form data for precise theories and formal propositions. All the theories mentioned only correspond to certain special cases out of a great number of others, in a long series, whose combinations are often far from being manifest. The mania of many authors for the construction of positive and generally applicable propositions or theses as to the nature of the action of chloroform, and the original causes of death by chloroform, appears to us to originate in a fault}" con- ception of the physiology of the subject. Our present task is to treat of those circumstances in which experience teaches us that the unfavorable effects of chloroform are manifested, as if by preference ; whilst we purposely neglect, for the reason assigned above, any further consideration of the primary physiological causes of death by chloroform. In our opinion, these causes have nothing to do with the etiology. The cases of poisoning by chloroform which occur in medical practice are, for the most part, cases in which chloroform is made use of for surgical purposes. It is not always in the power of the surgeon, who seeks to utilize a part of the poison- ous action of this agent, to exactly limit its operation, so as to shut out the unfavorable and unwished-for part of the same action. In a smaller number of cases, latterly becoming more numer- ous, poisoning by chloroform occurs either to medical men, or to others who take it either for suicidal purposes or with the 1 On Death from Chloroform. Medical Times and Gazette. 1870, July 23, p. 85. ANAESTHETICS.—CHLOROFORM. 425 object of gaining sleep, which they have in vain sought to obtain by other means. Lastly, we have lately met with cases in which chloroform, having been long taken as a sort of intoxicating agent (Genuss- mittel), for the pleasure it affords, has at last given rise to a kind of chronic poisoning. There are also a few cases of poi- soning by chloroform which have originated in its being acci- dentally mistaken for some other fluid. The statistics of death by chloroform in surgical operations have been very carefully collected by many observers for some few years past.1 The numbers already collected relieve us from the necessit}' of discussing the question whether chloroform itself is really a cause of death, in spite of the well-known dictum of Sedillot, "Le chloroforme pur et bien employe ne tue jamais." The question, as to which stage of chloroform narcosis is most exposed to the danger of death, has been much and freely dis- cussed. Apart from those rare cases in which the true cause of death must be sought, not in the chloroform used, but in what is called "shock," occurring after severe accidents, and sometimes occurring in very sensitive people—cases which ought properly to be excluded from, our consideration—we shall be very nearly right if we admit, with Billroth, that death may occur in all stages of narcosis. But the statistical material at our disposal does not allow us to draw any absolute conclusions from it, as regards this point. The following figures are taken from Sansom 2 and the Report of the Chloro- form Committee.3 The first author gives the following table: Stage of the Operation in which Death occurred. Before the operation began. During the operation...... Soon after the operation ... 18 22 6 22 6 12 14 14 1 It appears to us quite unnecessary to consider in any detail the now celebrated controversy as to the relative merits of ether and chloroform. It is very likely already decided, whilst we write this, in favor of chloroform [—not in America; see foot-note, p. 443J. 2 Loc. cit. p. 65. s Loc cit. p. 374. 426 BOEHM.—POISONS. The Chloroform Committee collected 109 cases, of which there died : At the beginning of the inhalation......................... !" In the stage of excitement.......................-........ 16 Under imperfect anaesthesia............................... 24 With perfect chloroform narcosis.......................... 38 After the operation was over.............................. 14 Not known at what period................................ ? 109 or, Before they were perfectly under chloroform................ 50 During chloroform narcosis............................... 52 Condition not known..................................... ? 109 The fact, first specially noticed by English authors, that an overwhelming majority of the fatal cases are in males, is very remarkable. The proportion between men and women, accord- ing to the statistical materials furnished us by Sansom,1 is as follows: According to Snow................... 3 males to 2 females. " Scoutteten............... 2 " 1 female. Kidd................... 4 " 1 " Sansom..........'....... 2.8 " 1 " " Committee..............72 " 37 females. Sansom justly remarks that this result is all the more remark- able, inasmuch as the obstetric use of chloroform in childbirth has given women almost a monopoly in its use. The age of the individual does not seem to have any special influence. That very young children bear chloroform extremely well, as a rule, is evident from the hare-lip operations one so often sees [and from the experience of ophthalmic hospitals, no- tably Moorfields.—Trans.]. It would, however, be rash to decide on these grounds that children under five years of age possess an absolute immunity from the ill effects of chloroform. Indeed, there have been cases observed of late which show the contrary result, and perfectly justify Bouvier's2 caution to neglect none of the usual precautions, when administering chloroform to small children. 1 Loc. cit. p. 67. * Bulletin de Therapeutique. Aug. 1867. ANAESTHETICS.—CHLOROFORM. 427 The statistics of the Chloroform Committee (and we have as yet no others which we can trust) only show that most chloro- form deaths occur precisely in those periods of life in which the greatest number of men are chloroformed. Under 5 years there died................ 0 From 5-15 " " " ............. g " 15-30 « " «..........'.'.'.'.'.'!!!;;;!!!;; 3o .......................... 32 .......................... 12 " 30-45 " " 45-60 " Over 60 " At unknown ages . 24 109 Constitution and physical strength seem to stand in this peculiar relation to chloroform, that robust and healthy systems seem far more exposed to the dangerous effects of this material than delicate, weakly men who have been reduced by previous ill-health. Sansom1 discovers in this a certain "law of toler- ance." As a result of this law, chloroform is far less dangerous for women and children than for men. We may also explain in a similar way the fact that the largest relative number of fatal cases of chloroform administration have occurred in cases of very trilling surgical operations, minor cases, such as the extrac- tion of teeth, the operation for removal of ingrowing nail, and such like, where for the most part the general health of the patients has been tolerably good. Sansom collected 107 cases of death from chloroform, in which the reasons for which it was given are assigned, and from these it appears that I. After very slight operations there died............................. 62 II. " more severe " " " ............................. 26 III. " "capital" " (amputations, lithotomy, etc.) there died... 7 IV. " herniotomy, forceps-labors, there died........................ 69 V. Delirium tremens and mania, there died............................ 4 VI. Natural labor, there died......................................... 2 107 1 Loc. cit. p. 68. [In my copy this reads "Reduction of dislocations (5); forcible extension, 6." Instrumental labors go in class II., and herniotomy in class III.—Trans.] 428 BOEHM.—POISONS. Our space does not allow us to enter at greater length into Sansom's arguments on this point. An objection may fairly be raised that the total number of cases col- lected is not sufficient to allow of safe conclusions. And again, it may be said that minor operations are far more common than more severe ones, and must therefore, in the nature of things, furnish a larger number of fatal cases. For these reasons it is perhaps well not to lay too much stress on the " catholicity " of the " principle of tolerance." It is not possible to say exactly Iioav much chloroform can be given to any one without danger to life, because it is in most cases quite impossible to accurately estimate between the quan- tity of chloroform used and that actually inhaled, or, in other words, absorbed (resorbirt). However, all authorities agree in this, that the degree of concentration of the chloroform vapor, the more or less perfect absence of atmospheric air in the respir- atory medium, is of special importance. That concentrated vapors can destroy animal life in an exceedingly short space of time has been many times demonstrated by actual experiments ; surgical experience leads to the same conclusion. On the other hand, the actual quantity of chloroform inhaled, if spread over a longer space of time, is of less importance, and Sansom 1 calls attention to the fact that death very commonly occurs after only a few whiffs of the chloroform, and much more rarely in the later stages of narcosis. The figures given by the Chloroform Committee can scarcely be said to confirm this. Our OAvn view is, that on this point also we must suspend our judg- ment. This much is, however, thoroughly established by cases, that very large quantities of chloroform may be inhaled safely enough, whilst very frequently quantities AAdiich are very moder- ate indeed may bring about fatal accidents.3 It is almost equally difficult to determine what is a fatal dose of chloroform, when taken into the mouth, and swallowed as a liquid. In six cases of this sort which ended fatally, from one- half to eight and a half fluidrachms of pure chloroform were taken. Ever since chloroform has been popularized in surgical 1 Loc. cit. p. 73. 2 It is scarcely necessary to dilate upon what is called "idiosyncrasy" with regard to chloroform as a primary cause of its injurious effects. ANAESTHETICS.—CHLOROFORM. 429 practice, the general experience of medical men has confirmed their belief that certain morbid states of the system are particu- larly liable to danger from chloroform narcosis. Amongst these special prominence must be given to anoma- lous conditions of the heart. Here, too, we must admit that in.many cases "post hoc, ergo propter hoc," has led to erroneous conclusions. Sansom' insists, and rightly so, we think, that simple valvular incompetency, in the absence of fatty degenera- tion of the cardiac muscles, does not render chloroform more dangerous, or contraindicate its use. This opinion has been amply corroborated by practical experience. But unfortunately the one pathological condition of the heart which seems to be really a predisposing cause of the bad effects of the narcosis- fatty degeneration of the cardiac muscles—is, as a rule, diagnosed first on the post-mortem table. Indeed, as regards this, we can scarcely talk of clinical experience, as Koehler does (loc. cit. 2. Article, p. 25). Indeed, no case is known to have been chloro- formed in spite of a previous diagnosis of " fatty heart," and then, after death, this condition to have been found. But this is what we should understand, when we are told of clinical experience being confirmed. That 21 out of 55 cases exhibited fatty hearts when examined post-mortem is just as much to the point as Kidd's experience, that, in 250 cases of sudden death, he never found a single case of degeneration of the heart. Whenever it is possible to diagnose this condition with absolute certainty, we shall hold clinical observers inexcusable, if they exhibit chloroform in such cases. But at present the fact that chloroform is injurious in fatty degeneration of the heart is a result, not of clinical experience, but of post-mortem pathology. Sansom (loc. cit., p. 76) has collected 5.1 post-mortem records of fatal cases of chloroform, with special reference to the condition of the heart. In 21 cases the heart was perfectly normal; there was fatty degeneration in 18; in 14 it was pale, soft and flabby; and in two cases there was valvular incompetency. No one as yet has actually proved that the cardiac changes in any case have been the primary cause of the death from chloroform. There is also a general agreement amongst authors, as to this, that alcoholism may greatly increase the dangers of chloroform narcosis. This has been observed not only in the cases where chloroform has been given to calm the excitement of delirium 1 Loc. cit. p. 77. 430 BOEHM.—POISONS. tremens, but also in surgical operations on drinkers, in whom chloroform narcosis is generally very difficult to induce, and runs an irregular and unfavorable course. Kidd (loc. cit.) has collected nine cases in which chloroform, used as a remedy in delirium tremens, proved fatal; and Sansom (loc. cit.) has brought together eight other cases in which chloroform, administered to habitual drinkers for surgical operations, ended fatally. Without disputing that alcoholism may serve as a predisposing cause of death from chloroform, we must add that it is not safe to assume that all these cases really died on this account. For, Avhenever a death occurs from chloroform, Ave can easily understand that every effort will be made to remove a part, at least, of the blame from the chloroform itself, and the mode in which it was admin- istered, and thus undue significance may be given to such con- ditions as the one named. Our experience has furnished us with eases enough in which regular sots, who exhibited great resistance to the effects of chloroform, have inhaled great quantities with- out a trace of injury from it. English authors (SnoAv, Sansom, and the Report of the Chloro- form Committee) lay great stress on the different methods and modifications of inhalation, as regards the amount of danger. But in regard to this the real point of importance is the con- centration of the vapor and the amount of admixture of atmo- spheric air. Let the circumstances be what they may, the most dangerous of all methods is the administration of chloroform to one's self. We must now sketch briefly the symptoms of chloroform narcosis in its various stages, and the effects of chloroform in human beings. The first subjective symptoms, which are noticed almost immediately Avhen chloroform is brought close to a patient, are a burning feeling in the nose and conjunctiva and a remarkably sweet taste in the mouth. Tears and saliva are generally secreted more abundantly, and the latter most generally causes efforts to swallow, which frequently bring considerable quantities of chloroform, in the gaseous form, into the stomach, which may at once induce vomiting. If the air charged with chloroform be now breathed continu- ANAESTHETICS.—CHLOROFORM. 431 ously for some little time, we get in different individuals a number of symptoms, which are as multiform, indefinite, and varying as the psychical conditions of the individuals ; they defy any precise description or analysis. All we can do is to describe some of the chief characteristics, and point to some of the varieties brought about by individuality and external con- ditions. In most of those who are chloroformed, there is observed during the so-called first stage, or stage of excitement, a striking alteration in behavior and in the expression of their feelings. Most commonly this change of feeling is a cheerful one, mani- fested by laughing, gay gestures, singing, etc., but it is not rare to find the patient melancholy, weeping and wailing, and some- times very angry, and there may sometimes be temporary mania. It is impossible to say on what this behavior depends, or why it assumes such different aspects in different cases. People who are usually cheerful become lachrymose, mild people get angry, modest and retiring people get bold and shameless, and vice versa, in manifold and complex variety. Just in the same way, under the influence of chloroform narcosis, the patient's charac- ter alternates from grave to ga}^, from lively to severe. It is, indeed, indisputable that this condition strongly resembles the slighter degrees of alcoholic intoxication. Those who divide chloroform narcosis into several clearly de- fined stages do, in fact, prefer method to truth. Their picture is clearly draAvn, and its colors are bright, but it is not like nature! For example, even the first stage, which Ave have been trying to sketch, is very different in different people, if we investigate the amount of consciousness, the degree of mental activity and of sensibility, etc. As a rule, the senses are not much affected in the very beginning. But their activity is very soon affected. Those who are chloroformed very soon become conscious that their senses are rendered more acute—there is a peculiar sharp- ness about them, a vast increase in the force of particular sensa- tions ; for example, the ticking of a watch seems like strokes of a sledge-hammer ; not infrequently the words that bystanders whisper gently are heard with amazing distinctness. Other senses besides hearing are sometimes, but less commonly, inten- 432 BOEHM. —POISONS. sified in a similar way. The sense of sight, as a rule, is affected in an exactly contrary manner—a cloud seems to come over the eyes, and prevents the objects around from being seen clearly, and at last things seem to be all jumbled up together. Taste very soon becomes as it Avere lost, and at last all the senses be- come more or less impaired and defective. As a rule, conscious- ness remains intact during this first stage, although necessarily affected by the false coloring of the anomalous sensations Ave have described. The reflective faculties are therefore unimpair- ed, so that questions are answered correctly. Indeed, there are many men avIio give correct answers during this stage as regards their sensations. But many others are so altered as to be quite oblivious of those around them, or of the circumstances in which they are. In their condition of half-aAvake and half-asleep, they busy themselves with the past, "wear their heart upon their sleeve," and declaim loudly like those under delusions, or as if they were dreaming aloud ; they sing and pray as though they were in church, and answer incorrectly, or not at all, when they are questioned. Lastly, although such cases are rare, we meet with those A\dio, after inhaling a few whiffs of chloroform, fall rapidly into a deep slumber, without any trace of a preliminary stage of excitement. The objective symptoms of this first stage are, as a rule, exceedingly well marked. The face is flushed, the forehead bedewed with perspiration, the pupils are manifestly contracted, and the body makes either definite, voluntary, and well-co-ordinated movements (tries to rise up, walk, hit out, etc.), or is moved spasmodically (generally with extreme tension of muscles) hither and thither with no apparent object. Hiccups and vomiting often set in, the pulse seems somewhat quickened, and its resistance in general diminished. During this stage sensation, too, is by no means uniformly affected. Many patients complain of crawling sensations (formi- cation), like insects crawling over them, felt in the extremities, and unpleasant feelings of pricking and stinging in the skin— symptoms which are generally associated even then with dimin- ished sensibility to external irritants. Partial or complete an- sesthesia of the skin has frequently been observed even in this early stage. ANAESTHETICS. —CHLOROFORM. 433 The duration of this stage of excitement seems to be subject to no rule, and the limits of variation are very wide, and do not seem at all definite. If the inhalation be vigorously pushed, it is commonly found that a very few minutes suffice to change the scene. The previous excitement is either suddenly or more gradually allayed; the talking, singing, swearing, and so forth, is hushed, the muscles become relaxed and limp, the arms are dropped, the flush on the face vanishes, and deep sleep is indi- cated by very audible snoring. The relaxation of the muscles very soon extends all over the body. The masseter muscles perhaps resist the longest. Breath- ing is deep and slow, as in those who sleep; the movements of the heart are somewhat weakened, but still regular. The pupils now become some whatdilated, and when narcosis is quite com- plete the ball of the eye can be touched without exciting any reflex movements of the eyelids ; there is, in fact, perfect anaes- thesia, and we may now use the surgical saw or the knife or the actual cautery without the patient being at all conscious of it, and without exciting any reflex movements. The general rule seems to be that sensibility lingers longest in the region of the sensory branches of the trigeminal (fifth) nerve, at the tip of the nose, and in the two temporal regions. The lower limbs and other parts of the body may be quite insensible to pain, Avhilst the corneal conjunctiva still gives rise, when touched, to active movements of a reflex nature. It is therefore quite unnecessary in surgical operations to delay the beginning of the operation till such time as the eyeball becomes insensible. If the chloroform be pushed still further, it is very easy to reach a third and very undesirable stage, in which death occurs, for the most part, very suddenly, sometimes under the guise of syncope, sometimes taking the form of asphyxia. Herein lies the special risk of chloroform, that danger comes before it is expected, and that what we call unfavorable or dangerous symp- toms are generally the immediate forerunners of death. In fact, death treads on the heel of danger. A sudden stoppage of the pulse or breathing, a sudden paleness overspreading the face, cyanosis or duskiness of the lips and dilatation of the pupils, and sometimes sudden relaxation of the sphincters, the passage VOL. XVII.—28 4;;4 BOEHM.—POISONS. of urine and ffeces, vomiting, a sudden stoppage of the flow of blood during an operation—these are the alarm-signals ; and of'these sometimes one, sometimes another, most prominently attracts the attention of the by-standers. We have previously discussed the physiological questions concerned in this condi- tion. We need only repeat here, that it is by no means easy to say, in any given case, whether cardiac paralysis (syncope) or the respiratory centre has brought about the unfortunate ending. We may grant that the first method is the commoner one, and at the same time the more quickly fatal one, since attempts at resuscitation are generally quite useless ; whilst anomalies of respiration, conditions of apncea, or mechanical obstruction to breathing, in consequence of paralysis of the tongue and of its falling back and obstructing the aperture of the glottis, and similar conditions, can generally be remedied by appropriate means. In the first class of cases the face, as a rule, grows pale, and we note a stoppage or irregularity of the pulse, whilst res- piration continues a little longer; in-the latter class of cases, the various disturbances of respiration and the interruption of the breathing precede the stoppage of the pulse. Death is not seldom quite sudden. Violent cramp-like muscular movements must also be regarded as an unfavorable symptom, which com- monly ends with the patient's dying suddenly. Sansom (loc. cit. p. 92) remarks that this is particularly likely to occur in those patients who have tippled freely, and in whom it is very difficult to induce narcosis. We have previously insisted that we can as yet give no pre- cise rule as to which stage of chloroform narcosis is the most dangerous. Indeed, there are not wanting authors who insist that the unfortunate cases are more apt to occur at the very beginning of the chloroforming (often, indeed, after only a whiff or two of it) than they are in the later stages. We now return to the cases in which the desired narcosis is obtained without any untoward complications. If the inhalation be discontinued, the narcotized patient generally awakes sud- denly, as from a deep sleep, in from one-half to three-quarters of an hour, without the faintest knowledge of what has befallen him in the interval. After some slight delirium and confusion, ANAESTHETICS. —CHLOROFORM. 435 the senses gradually return. Vomiting often occurs in these cases, but there is seldom any other abnormity. Serious sequelae are hardly ever known to occur. In rare cases, how- ever, the course of the narcosis is so far abnormal as to be com- plicated by general convulsions, of varying severity. These con- vulsions, which are sometimes epileptiform, and sometimes of a tetanic nature, may sometimes be sources of considerable dan- ger, in so far as they involve more or less deeply the muscles of respiration. The real nature and cause of these convulsions is at present simply conjectural. We must briefly consider those cases which are remarkable, either for the unusually long duration of the narcosis, or for the persistence, when the narcosis is over, of certain anomalies of the nervous system, such as anaesthesias, paralyses, and the like, for more or less time. All these modifications point to individual peculiarities in the constitution of the nerve-centres, and have been noticed to occur occasionally as after-effects of most nar- cotic poisons. Although the published cases have been recorded less accu- rately than we could wish, it is no longer possible to deny the existence of a peculiar chronic form of poisoning or intoxication by chloroform (chloroform drunkenness). For the most part this consists in the ordinary use or abuse of large quantities of this narcotic, which is first employed for therapeutic purposes (the relief of pain, or to procure sleep, etc.), and gradually becomes an almost absolute necessity to the morbidly altered nervous system, as is the case, although in still more marked a manner, with alcohol and opium. The cases of this kind observed up to the present time present symptoms of mental (or psychical) alienation, and are more particularly of the class denomi- nated periodic psychoses, to which the abuse of chloroform seems to predispose. This was at all events unmistakably evident in a case which fell under our own observation. Perfectly free and lucid intervals alternated in this case with attacks of the most intense melancholy and delusions as to persecution, leading to several attempts at self-destruction. No chloroform was consumed in the free intervals. Biichner's case (Husemann, loc. cit p. 682) also took the form of periodic mania. Two other cases by Merie (loc. cit.) and Vigla (Med. Times, Nov. 21, 1855), in the first of which about a pound every five days, in the latter from twelve to fourteen drachms daily of chloroform were used, were, it would seem, of a different kind. 436 BOEHM. —POISONS. Merie's case appeared to e one of extreme moral depravity, a sort of moral insan- ity. The patient, who had formerly taken morphia, gradually became unable to procure sleep in this way, and so betook himself to chloroform. He laid in bed nearly all day, and chloroformed himself whenever he woke. At last he acci- dentally fractured both thighs; these had to be amputated, and this was done under chloroform, which acted very nicely for this purpose. He finally sank with symptoms of general marasmus. In Vigla's case there was also a peculiar kind of insanity. It appears by no means an unusual thing for people who thus intoxicate themselves with chloroform to begin with inhal- ing it only, and to go on to take it internally. This naturally leads us to make some brief remarks on the way in which chlo- roform affects the stomach. As regards this, our present infor- mation is by no means copious. The report of the Chloroform Committee (loc. cit.) contains four fatal cases, Tardieu's work on poisons,' three each of death and of recovery. Out of ten cases in all, seven ended fatally. The narcotic symptoms in these cases are, from obvious reasons, complicated by the local gastric affection, consisting in the vomiting of quantities of slimy, and sometimes bloody, matters, and of violent epigastric pains, etc. Simultaneously, it is usual to find the narcotic oper- ation of the poison fully developed, and in several of the cases the poisoned patient has been found in a condition of the deep- est coma, with dilated and immobile pupils, deadly coldness of the extremities, and almost imperceptible pulse. Death is some- times preceded by convulsions. The post-mortem appearances in those who die comatose from chloroform do not afford a single characteristic or pathog- nomonic sign. Whatever may have been set down as charac- teristic in the past, we now know is to be met with in many other kinds of death. We shall therefore waste no time in the discus- sion of this question. In cases where this poison is taken by the mouth, it is easy to understand that we shall find more or less severe lesions of the mucous membrane of the gastro-intestinal tract—sometimes only simple reddening, sometimes ecchymoses and signs of extensive and severe inflammation. The prophylaxis, or, in other words, the cautious application 1 Etude medico-legale et clinique sur l'empoisonnement. Paris. 1867. ANAESTHETICS.—CHLOROFORM. 437 of this narcotic, is the most practical and important part of the whole question. We cannot enter here on a detailed considera- tion of the principles on which the administration of chloroform (with safety) is founded. This is a subject which partly belongs to surgery, and partly to materia medica. An anxious and painstaking observation of both pulse and respirations, as well as of the external appearance and behavior of the patient under chloroform, with especial reference to those symptoms which we have spoken of before as indicating danger, should always, when chloroform is administered, be the special duty of an assistant skilled in this matter, who should have nothing else to do but to superintend the narcosis. In other words, whoever is giving chloroform should have nothing else to do but watch its effects and administration. A sufficient amount of atmospheric air mixed with the chloro- form all the while it is administered is indeed the chief element of safety. The moment any threatening symptoms are noticed, the chloroform must of course be immediately suspended. The proper treatment of poisoning by chloroform will, therefore, necessarily depend on either combating the tendency to death from cardiac paralysis, or on striving to recall the patient from a condition of asphyxia. In practice, however, these two objects are not so remote as they may seem to be in theory, since, as a rule, the cases in Avhich there is any considerable risk from symptoms of cardiac paralysis are cases in which also the busi- ness of respiration comes to a standstill. The practical signifi- cance of the distinction is lost if we reflect that the means of deliverance in both cases are very nearly identical. Widely as authors differ as to the mode in which death occurs in poisoning by chloroform, they all, Avith very few exceptions, agree in earnestly recommending that Ave should immediately and energically set about artificial respiration in all cases of threatened death from chloroform. Those who contend for the toxemic theory, which attributes the injurious effects of chloroform to the action of this agent in robbing the blood of its oxygen, make oxygen play the principal part in their therapeu- tic efforts, and some have recommended the inhalation of pure oxygen gas (Blanchet, Jackson, Ozanam, etc.). Those who, on 438 BOEHM.—POISONS. the contrary, regard chloroform as a direct nervine poison (Lalle- mand, Perrin, and Duroy), admit the advantages of this means of treatment, since the poison still present in the blood and nervous system may thus be taken into combination, although its elimination is hindered by the paresis of respiration. They even think that inhalations of nitrogen or hydrogen might be useful in this way. Another group of authors, whose views are intermediate between those named above, and who consider its action on the cardiac nerves and the muscular fibres of the heart as the real element of danger, still consider that in oxygen we have a salutary irritant, which may spur on or rouse up the heart, which has in one or other of these ways been paralyzed, to new activity. All these theoretical views appear to us unsatis- factory and crude. Let us be content, for the present, to establish this proposition, that in all cases where the natural respiration is deficient or wanting, we ought at once to set about artificial respiration. How far we act upon the heart and its movements in this way we cannot as yet determine. Nor need Ave enter into details as to the best Avay of instituting and carrying on artificial respira- tion. The proposal of C. O. Weber, to act upon the phrenic nerves in the neck by faradization with a fork-like electrode, simultaneously applying one electrode to the diaphragm, seems to us one of the most useful. It is warmly commended by Weber. Simple inflation of air and passive artificial respiration by up- and-down movements of the thorax, drawing the tongue forward at the same time with a pair of forceps, have been successful in many cases. If the heart has actually stopped beating, direct electro-puncture of the heart has been several times proposed, and carried out. It certainly deserves a trial in any case, and should be combined with artificial respiration. But we have not much reliable experience on this point, and besides, we cannot assume that the results obtained by experiments on animals will also follow in the case of human beings. When threatening symp- toms in chloroform narcosis have been marked by sudden col- lapse, pallor, apnoea, etc., it has generally been customary to apply strong irritants to the skin, in order to rouse the par- ANaESTHETICS.—SULPHURIC ETHER. 489 alyzed nervous system, and to stimulate it to its usual reflex action—of course combined with artificial respiration. Pouring or sprinkling of water, dropping ether on the skin, the appli^ cation of strong water of ammonia to the mucous membrane of the throat, all belong to this category. Sansom (loc. cit.) has lately opposed this sort of treatment, and especially recom- mended warmth as a means of resuscitation, combined with artificial respiration. But at the proper time—that is, imme- diately on the first indications of collapse setting in (small pulse, pale face, etc.)—the application of these means, or the mere sprinkling of cold water, does most undoubtedly have a good effect. There is no medicinal treatment for cases of chloroform poisoning, because we know of no direct antidote to chloroform. Cases of poisoning by the internal administration of chloroform must be treated on general principles.1 CHAPTER III. POISONING BY ETHER (SULPHURIC ETHER—DI-ETHYL ETHER— aETHER SULPHURICUS). Ether, which is a colorless and extremely mobile fluid (C4H10O) has a very much lower boiling point than chloroform. The latter boils at 62° C. = 143.6° F., whilst ether boils at only 35° C. = 95° F. It is also of much less specific gravity than either chloroform or water, very volatile, and the vapor diffuses a very intense characteristic odor, which can be recognized clearly when very much diluted. Ether does not mix with water, but it is miscible with alcohol in all proportions. Like chloroform, ether can gain access in a gaseous form to the blood, through the surface of the organs of respiration, both in human beings and in other animals. 1 In a case of this kind, where an old man hnd swallowed nearly one ounce and a half of chloroform, I administered oil, and then solution of sulphate of zinc with the stomach-pump, afterwards demulcents and stimulants per rectum. He recovered.— Trans. 440 BOEHM.—POISONS. Absorption from the mucous and serous membranes takes place more slowly. It has been found, when it is introduced into the stomach, rectum, or serous cavities, that very much larger quantities of ether are required to produce its characteristic effects than when it is inhaled. Anstiel strives to explain this in the following way : When it is introduced through mucous or serous membranes, the ether which is absorbed must necessarily pass through the portal system of veins and the lesser cir- culation, before it can get into the arteries, and thus reach the seat of its operations. From this we may infer that small quan- tities of ether may be discharged from the lungs before any effect on the general system is produced. Indeed, the elimination of ether by the lungs has been repeatedly determined by experi- ments (Snow, Anstie, Lallemand, etc.); it has also been found in urine, though in very small quantities. In this way it has been established that a very large quantity of the ether which is taken in leaves the body in the same form, quite unchanged. Whether the remainder is decomposed in the body is as yet unknown. The effects of ether on the blood are essentially the same as those already mentioned when discussing chloroform, with the excep- tion of the peculiar compound described by Schmiedeberg (loc. cit.), as occurring between one constituent of the blood and chloroform. No similar compound has been described as occur- ring with ether. Like chloroform and alcohol, the effect of ether on blood is to retard the giving up of its oxygen to reduc- ing agents (Bonwetsch, loc. cit.). The blood of etherized animals has a remarkably dark, venous appearance. The effects of ether are partly due to its remarkable rapidity of evaporation, produc- ing a fall of temperature, and partly to a peculiar, and as yet unexplained property possessed by ether of acting as an irritant on the terminations of the sensory nerves in human beings. Since ether boils at (or even below) the temperature of the body, there is this danger when introducing large quantities of fluid ether into the stomach, that through the expansion of its vapor the intestines may be so greatly distended that the respiratory movements of the diaphragm may be thus rendered impossible. 1 Stimulants and Narcotics. London. 1864. ANaESTHETICS.—SULPHURIC ETHER. 441 Claude .Bernard1 has shoAvn that the functions of secretins organs are rendered more active by ether when this substance is applied in or near the locality of their excretory ducts. For example, the gastric juice, the pancreatic juice, saliva, etc., are much increased in quantity when it is given internally to ani- mals. Glycosuria is very commonly, though not constantly, pro- duced by ether ; whether we consider, with Claude Bernard, that this symptom is also to be regarded as a phenomenon of irrita- tion, and as the expression of an increased secretory activity of the liver, or whether, with Anstie, we should regard it as a sign of weakened functions, a sort of paralysis or narcosis of the liver, we will not attempt to decide. In any case, the production of diabetes by ether must be classed along with the other forms of diabetes due to the action of poisons, regarding which we unfor- tunately as yet know very little. Although the other local effects of ether are of little interest from a toxicological point of view, the general effects of this substance agree in most points with those of chloroform and other anaesthetics. Here, too, we must regard them as essentially due to the general operation of a change in the functions of the nerve-centres, of the exact nature of which our present knowledge is extremely limited. Here, too, an exalted sensibility of individual nerve-centres precedes the more or less perfect suspension of consciousness, and the loss of the knowledge of things external to the patient. The long-discussed, and as yet unsettled question, as to whether ether or chloroform is best fitted for the production of surgical anaesthesias and for other therapeutic purposes, or which is the safer of the two, has instigated numerous experi- ments on the physiological effects of ether. There is a pretty general agreement that large quantities of ether are required for the production of perfect anaesthesia. The chief difference between ether and chloroform seems to be the opinion advanced by most of the experimenters as to the relation of ether to the activity of the heart. Whilst chloroform admittedly kills in not a few instances by bringing about a stoppage of the heart, ether almost always proves fatal by paralyzing the respiratory 1 Lecons sur les effets, etc. loc. cit. 442 BOEHM.—POISONS. centres. Anstie (loc. cit.) lays special stress on the way in which ether affects the sympathetic nerves—which is shown by the red- dening of the face, the breaking out of perspiration, increased secretion of saliva, and increase in the frequency of the pulse. Unfortunately, there are as yet no conclusive experiments in this direction, so as to set the question at rest whether these phenomena do really depend upon the implication of the sym- pathetic nerve. As regards the order in which the functions of various parts of the nervous system are affected, or one may say abrogated, by ether, Flourens'and Snow2 state that, in the first instance, the peripheral sensibility and the co-ordination of the voluntary muscles are affected and abolished, and in such a manner that sensibility in parts at a distance from the brain and spinal cord lose sensation earlier than organs which lie nearer to these. Then follows suspension of consciousness, and last of all, the breathing is suspended. The movements of the heart go on some time after respiration has ceased. Valuable as all this may be from a practical point of view, it is yet clear that we are still in want of more definite knowledge, to enable us to draw any very accurate distinctions or conclusions between these different anaesthetics and their operation. The etiology of ether poisoning differs only very slightly from that of poisoning by chloroform. Most of the cases occur from its medicinal or surgical use in those places Avhere it is preferred to chloroform. Besides this, the internal use of ether (Hoffmann's anodyne) may lead to poisoning. It must also not be forgotten that in some coun- tries (north of Ireland) ether is taken as a sort of luxury, to in- duce narcosis ; and it is very easy to understand that poisoning cases may occur in this way. In spite of all this, the published cases of poisoning by ether are very few, and bear no comparison at all with the numbers of cases of poisoning by chloroform. However, this is not so much due to the greater safety of ether, but rather to the fact that whilst the use of ether has steadily diminished, that of chloro- 1 Compt. rend. XXIV. » Chloroform, etc. loc. cit ANaESTHETICS.—SULPHURIC ETHER. 443 form has as constantly increased. [We doubt if this be true of the last two or three years in the British Islands.—Trans.] ' Neither the poisonous nor the fatal dose of ether has yet been determined, and we therefore refrain from giving figures which can only be founded on isolated cases. At least half an ounce of ether is required to fully anaesthetize a grown-up person, and, as a rule, considerably more. Just as it is with chloroform, so is the case with ether: the degree of concentration of the vapor and the amount of atmospheric air mixed with it are the chief matters of moment. The symptoms of ether narcosis are pretty well known, partly from observations on patients, and partly from the exper- iments of those who have taken it themselves (Anstie). All agree in giving prominence to the unpleasant odor of ether, which is probably one of the chief obstacles to its general use as an anaesthetic. The first symptoms verified by Anstie in several experiments upon himself were a general feeling of exhilaration of spirits, with an inclination to laugh, a pleasant feeling of warmth, extending all over the body, and palpitation of the heart, with increased frequency of pulse. This is soon succeeded by a feeling of numbness and pricking sensations, commencing with the lower extremities, quickly running all over the body, with a breaking out of perspiration on the forehead. Surround- ing objects began to dance before his eyes ; he was unable to con- trol or verify the movements of his hands, and felt as if there were enormous weights on all his limbs. Then he lost conscious- ness. From the observations made by him it would seem that he lost the power of writing as early as about forty seconds after the beginning of the inhalation, and that the narcosis from inhal- 1 The enormous clinical experience with ether in America (seemingly unknown to German authors) overwhelmingly disproves the inference above made. There is no es- cape from the conviction that ether kills so seldom, simply because it is so safe. As ad- mitted by the author, ether almost never primarily paralyzes the heart, and its only dan- gerous effect—stoppage of respiration—is one easily foreseen by striking premonitory symptoms, and readily and surely relieved by the simple means of removing the anass- thetic and making a few passes of artificial respiration. New York surgeons, thus con- vinced of the vastly greater safety of ether, very generally prefer it to chloroform, and the same is probably true of the majority of American practitioners.—Edw. Curtts. 444 BO EH M. —POISONS. ing half an ounce of ether had lasted thirty-five minutes before he again recovered consciousness. When he first recovered con- sciousness he felt unable to move, and had a feeling of crawling (like insects creeping) in the limbs ; in a few minutes more, how- ever, he felt perfectly himself again. In other cases, a great degree of motorial excitement has been observed in the first stage of the operation of ether, along with unconnected speech, laughing and crying, just as is often ob- served in narcosis from chloroform. The flushing of the face, the occurrence of sweating, the increased frequency of the pulse, are matters on which most authors are agreed. In cases which have ended fatally, there has usually been noticed a sudden stoppage of the breathing, which is, as a rule, not much affected in the ordinary cases. But stertorous breath- ing has sometimes preceded death. Convulsions have not been observed in these cases. The pupils, which have either been contracted or unaltered during the normal narcosis, have suddenly dilated at the moment of death. Martin' has recorded a case of chronic poisoning by ether in a woman who took large quantities of ether (internally) on ac- count of pains in the stomach. Her symptoms consisted of tremor, formication, pains in the chest, and muscular weakness —all of which soon vanished entirely on the removal of their cause. The post-mortem appearances present nothing peculiar, ex- cept a very perceptible smell of ether, which is scarcely ever absent, and is known to persist for some time after death. There are no other characteristic symptoms. The treatment must be similar to that of poisoning by chloro- form. . 1 Virchow und Hirsch, Jahresbericht {Husemann). 1870. ANaESTHETICS.—CHLORAL HYDRATE. 445 CHAPTER IV. POISONING BY CHLORAL HYDRATE. The more this anaesthetic, introduced into surgical practice by Liebreich' in 1869, has grown into favor with medical prac- titioners, the more indubitably, though slowly, has its nature as a poison come into notice ; partly from observations on patients, and partly by pharmacological experiments. Although this new remedy is a very valuable one, we have learned by the experience of the last few years that its use is not always devoid of danger even in the most skilful hands. The more firmly it is established as a remedial means of undoubted usefulness, the more incumbent is it on toxicologists to discover its injurious effects, and to study the circumstances which cause these to replace the beneficial results which are wished for when it is prescribed. The hydrate of chloral (02C130H, +H20) is met with in the form of white crystals, which possess more or less of a characteristic penetrating smell, according to the purity of the substance. It is easily soluble in water, and the solution is neutral to test-paper, and gives rise to a peculiar aromatic and rather unpleasant taste, which is associated with a feeling of scratching or soreness in the throat. It is now manufactured in very large quantities for medicinal use. Chloral is absorbed and received into the general circulation in the same way as all other bodies which are soluble in water and diffusible. It is subject to the ordinary laws of diffusion, and its absorption is therefore possible wherever an exchange can take place between its solution and the fluids of the body ; it can therefore be absorbed by mucous and serous membranes, and in the subcutaneous areolar tissue. The absorption through serous membranes is the slowest of all. Porta2 has never seen the general effects of chloral after the injection of a considerable quantity into the sac of a hydrocele, though he has done this 1 Das Chloralhydrat, etc. Berlin. 1869. '* HvAemann, Ueber Chloralhydrat. Schmidt's Jahrb. Bd. 151. 1871. 446 BOEHM.—POISONS. experiment repeatedly. As it is volatile, though only slightly so, a small portion may pass into the blood in the form of vapor, through the membrane of the air-cells of the lungs. The ques- tion, in what way and in what form chloral is eliminated from the bodies of animals is not yet settled, in spite of numerous experiments. Liebreich found neither chloroform nor chloral in the urine of animals poisoned with chloral. On the other hand, he found an increase of the chlorides. Byasson says that he has found salts of formic acid. Hammarsten* also found no chloral in the urine, and none at all in the expired air, but he found it in the blood of animals thus poisoned. Hermann * has lately succeeded in showing, by means of the isocyanphenyl reaction of Hofmann, that small quantities of chloral are present in the urine of men who are chloralized. No trace of chloroform was discovered by him in the fluid. Liebreich's theory that chloral is decomposed in the blood into chloroform and formic acid has given rise to a long series of researches, the general result of which is best expressed by say- ing that the question must still be regarded as an open one. The similarity in the effects of chloroform and of chloral, and the fact that this splitting up of chloral does occur in alkaline fluids, justify the opinion that some similar process occurs in the blood Avhen chloral is taken. Hammarsten, Porta, Gubler, and others have, however, rendered it pretty certain that we must not reckon the blood as identical with alkaline solutions merely because its reaction is alkaline. Hammarsten could find no chloroform in either the blood or the expired air of chloralized animals. Radjewsky3 and Frln. Tomascewicz4 met with similar negative results in relation to the elimination of chloroform by the lungs in such cases. The latter made use of the very delicate reagent of Hofmann in the tests which she carried out in Her- mann's Institute. Richardson, Roussin, Personne, and Byas- son6 met with positive results, in consequence of which they 1 Compare Husemann, loc. cit 8 Experiment. Toxikolog. p. 272. 3 Centralblatt f. d. med. Wissenschaften. 1870. 4 Hermann, Experiment. Toxikol. * Compare L. Lissonde, De chloral hydrate, etc. Paris, 1874. Lissonde, certainly AXaESTHE'JTCS.--CIILOKAL HYDRATE. 447 became defenders of Liebreich's theory. Hermann brings very grave objections against their experiments. There is another bod}r of the fatty eicids series, the trichloracetic acid, which is similarly split up by alkalies into chloroform, etc., and actually reckoned by Liebreich as a narcotic. It was, however, found to be absolutely devoid of narcotic properties by Hermann. In the same way he disposes of the narcotic action of iodal. According to Liebreicirs theory iodoform ought to be formed from this substance in the blood. It has, however, no narcotic action. Until further facts are knoAvn Ave must, therefore, leave any possible 'formation of chloroform out of sight in our explanation of the operation of chloral. Its effects are indeed similar to those of chloroform, but not more so than those of other organic chemical anaesthetics. We must, therefore, for the present, ac- cept chloral as a neAv member of a series of anaesthetics whose effects all have a family likeness, but can, in the present state of our knowledge, be only very imperfectly explained in either their physiological or their chemical relations. The stroma of the red blood-corpuscles is not dissolved by chloral, but swells up under its influence (Hermann). Ritter and Feltz,1 who injected different quantities of chloral into the veins of dogs, found, after repeated injections and long con- tinued narcosis, that the blood-corpuscles were misshapen and deprived of their elasticity. The plasma of the blood was col- ored red (haemoglobin in solution) and haemoglobin crystals very readily formed on object-glasses, and even the urine contained blood-coloring. Besides this, the blood had absorbed little more than half its normal proportion of oxygen. In a very concen- trated state, chloral has a corrosive or escharotic action; on fresh wounds, on muscles which are laid bare, on mucous mem- branes, and suppurating surfaces it produces a superficial white scab, and it causes redness and vesication of the skin when ap plied externally. without any idea of Hammarsten's experiments, mixed blood and bicarbonated salts and chloral together, and in both experiments obtained chloroform reactions. Hammarsten, however, shows that this is no proof that the same thing happens in the blood which circulates. 1 Bullet, general de th^rapeut. 1873. 448 BOEHM.—POISONS. From the remaining physiological investigations we learn that chloral, like all analogous remedies, very materially affects the functions of the higher nerve-centres, and in some circum- stances causes death by paralyzing the heart, or by stopping respiration. In animals of different classes it causes a diminished frequency of the heart's action, apparently by exciting the cere- bral origin of the vagus nerves ; in larger doses, it paralyzes the action of the heart (Radjewsky).1 In a similar way, small doses diminish the frequency of the respirations, whilst larger ones sometimes cause stertorous breath- ing and stoppage of breathing altogether. If we were to enter into details on these matters, we should have to repeat almost the very expressions we used when speaking, in relation to these effects, on the action of chloroform and ether. But we think Heidenhain's2 experiments, establishing the paralyzing effects of chloral on the centre for vascular nerves, are of great signifi- cance, because a great many of the injurious results of the therapeutic use of chloral can be explained by these. In experi- ments on animals, this paralysis is manifested by an enormous diminution of the arterial blood-pressure; in men, on the other hand, the feeling of weakness, and the ultimate failure of the radial pulses, point to considerable disturbances in the vaso- motor sphere. The practically interesting effects sometimes pro- duced by chloral on human beings, and more particularly in those mentally afflicted, will be discussed in their appropriate place. As yet, physiology has given no explanation of them. As chloral hydrate is still far too commonly prescribed in excessive doses, it is easy to explain why the majority of cases of poisoning by this substance occur in medical practice. Of late, however, both in England and Germany, there have been several cases in which it has been voluntarily taken by persons not in the medical profession. As a rule, these are persons who suffer from want of sleep (insomnia) and are delighted with this drug, but too commonly take it in excessive doses. If Ave con- sider how short a time has elapsed since the discovery of chloral, 1 Centralblatt fur die Med. Wissensch. 1870. 3 Pfliiger's Archiv. Bd. TV., p. 551, et seq. ANESTHETICS.—CHLORAL HYDRATE. 449 the great number of these unfortunate cases must not only strike us with surprise, but ought to furnish a strong motive for the exercise of caution in prescribing its use. All authors agree as to the great difference between the sus- ceptibility of different patients as regards the effects of chloral. There have even been known persons who appeared to be abso- lutely unaffected by this drug, and who have been able to take enormous quantities, not only without the usual effect, but with- out any injury accruing; and there are other cases where very small quantities have produced very unpleasant effects. The temperament or constitution of patients seems, according to our experience, not to have any effect in regard to susceptibility to the effects of chloral, although Porta (loc. cit.) holds that chil- dren and delicate patients are more amenable to its effects than others, which seems probable on a priori grounds. The only pathological conditions specially noted by writers on this subject as modifying the susceptibility to the influences of chloral are alcoholism and frequent indulgence in the use of stimulants. These greatly hinder the effects of chloral. Although chloral has been very largely used in psychical diseases, yet no very definite conclusions can as yet be drawn from this experi- ence. However, paralytic patients appear to be specially obnox- ious to the injurious effects of chloral on the vaso-motor nerves. Whether the injurious effects of chloral are most prone to occur in cases of failing heart and vascular degenerations (such as atheromatous and similar processes), is also not definitely settled, though it seems likely that such conditions may predispose to danger. It is also as yet undecided how far chloral exhibits what may be called a cumidative action, or whether it belongs to those substances to which the system gradually becomes accustomed. Although it is pretty well established that, if we desire to keep up the hypnotic action in long-continued use of chloral, we must go on increasing the doses, it is at least doubtful whether the power of the nervous system to resist its injurious effects increases in at all the same proportion. The phenomena of the so-called chronic poisoning by chloral (which we shall comment on by and by) do not by any means negative the idea of its accumulation in the system. The poisonous and fatal doses VOL. XVII.—29 450 BOEHM.—POISONS. of chloral hydrate can only be approximatively determined. We have gradually acquired by experience a knowledge of the fact that doses of seventy-seven grains, which used to be considered quite a safe dose for grown-up people, should by no means be prescribed as a mere matter of routine, nor indeed without very careful consideration. Indeed, fatal cases have occurred, not only from this dose, but from even smaller ones, and that quite suddenly. So far, therefore, as a general rule can be established, we must consider forty-six grains as the maximum limits for safety. For children and delicate adults, still smaller doses must clearly be prescribed. The symptoms produced by chloral, so long as they are sim- ply medicinal and salutary, are those of simple narcosis. This occurs, as a rule, without any particular stage of excitement, and without any peculiar subjective symptoms, in the form of a quiet sleep, the duration of which varies very greatly, according to the surroundings and the individual peculiarities of those who are chloralized. As a rule, there are no particular sequelae, and no recollection of the beginning of the sleep, or of dreams dur- ing the slumber. Occasionally it leaves behind it, for a short time, some headache, want of appetite, and muscular Aveakness. The objective phenomena of this moderate or normal chloral nar- cosis, are also not very characteristic. The temperature of the skin, and the frequency of the pulse and of the respirations, have been found diminished. The pupils are affected but slightly; sensation is not so keen as before, but is not so far abolished as to permit the performance of very painful operations. The excre- tions are not affected in any manner deserving of special notice. These symptoms, which are all more or less modified in special cases, are sometimes specially so by the occasional occurrence of symptoms of excitement, like those which are the rule in chloro- form narcosis. In such cases, the persons under the effects of chloral give one the impression of being drunk, because their excitement is manifested by talking, laughing, crying, and all sorts of movements. This stage of excitement may either grad- ually terminate in the return of consciousness or may pass into the customary narcotism. Even in cases where the symptoms of chloral narcosis are more noticeable, there is, as a rule, no strik- ANAESTHETICS.—CHLORAL HYDRATE. 451 ing outward warning of the approach of danger or death. It is far more common for these to set in suddenly, so that, for ex- ample, soon after the patient has taken the dose, or a little later, he sinks into a helpless condition, from which he never wakes again. More rarely death has been observed to be preceded by dyspnoea and stertorous breathing (thus approximating to the type of asphyxia). The symptoms of chronic poisoning by chloral, which have hitherto been noticed chiefly in asylums, may be divided into three distinct classes. In the first class we have the often observed disorders of digestion, induced by the long-continued use of chloral, and these are indisputably due to its local action as an irritant. When affections of this kind occur in persons who are already in a depressed bodily condition, especially in paralytics, it is easy to understand that they may prove somewhat serious, and even hasten the fatal termination. Pelmann has published cases of this kind. In one case jaundice supervened, and the patient died in seven days, having been somnolent nearly all the time. In the second group we may class the numerous cases of skin diseases observed after long use of chloral. They may assume the forms of various exanthems (erythema, urticaria, papulae, purpura, petechiae, etc.), and they clearly prove themselves to be exanthems due to poison (Intoxicationsexantheme), since they generally vanish again very quickly when the drug is dis- continued.1 With these we may class the cases in which the use of chloral has given rise to more or less extensive bedsores (see Reimer2). These have occurred, for the most part, in cases where the patient, after large doses of chloral, has lain a long time in one position. Reimer has observed the development of more or less deep ulcers and wounds from mere circumscribed redness and swelling of the skin, with the formation of blisters on the trochanters, knees, knuckles, tips of fingers, and even on the face and ears and other parts. Lastly, Schuele3 and Jolly4 1 Consult on this Husemann (loc. cit.) and the Jahresbericht iiber die Fortschritte, etc., of Virchow und Hirsch. 1871 and 1872 (art. Chloral). ' Allg. Zeitschrift fiir Psychiatric Bd. 28. 2. 1871. 3 Allg. Zeitschrift fur Psychiatric Bd. 28. 1. 1871. 4 Bayer, iirztl. Intell.-Blatt. 1«72. No. 14. 452 BOEHM.—POISONS. have quite recently observed a number of symptoms in lunatics treated with chloral, which must indisputably be referred to anomalies in the innervation of blood-vessels. Along with symptoms of increased action of the heart, gener- ally in consequence of very moderate use of spirits, there sud- denly occurred an erythematous blush, spreading itself over a large surface of skin, sometimes on the face, and then with hyperaemia of the conjunctivae and of the posterior surface of the eyes (retinae), and sometimes in other parts of the body. Schuele noticed at the same time a change of behavior in his patients. All these symptoms perfectly vanished when the chlo- ral was left off. If we exclude the gastric disorders, which are easily explicable, almost all the other symptoms of chronic chlo- ral poisoning may be referred to the anomalies of the circula- tion, which are brought about by the paralyzing influence of the chloral on the vaso-motor centre — on which we have before insisted so strongly. Even the tendency to bedsores may be thus explained. Hitherto no characteristic post-mortem appearances have been described in fatal cases of chloral poisoning. The treatment of cases of acute poisoning must clearly be analogous to that for poisoning by chloroform. For the chronic forms, as a rule, it is sufficient, along with appropriate regimen, to insist on a timely discontinuance of the drug which is the source of the mischief.1 CHAPTER V. POISONING BY SOME OTHER ANaESTHETICS. Besides chloral, chloroform, and ether, several other members of the so-called "Fatty Acids Series" have of late years sought introduction into medical and surgical practice. Although the majority of these have been introduced as substitutes for chloro- form, on the ground that they were free from the dangers which attend the use of this agent, yet most of them, as soon as they 1 See a paper by the translator in Vol. IV. of the St. Andrew's Medical Graduates' Transactions, p. 222. ANaESTHETICS.—AMYLENE. 453 have been put to the test, have proved at least quite as danger- ous, if not more so, than chloroform, which they were introduced to supersede. Repeated cases of death, attributable to their use, have up to the present time prevented any of them from obtaining anything like general acceptance from the profession. Most of these sub- stances agree in all essential points as regards their operation on the system and their properties, with what has been already ascribed to chloroform and ether. It will therefore suffice, for the present purposes of this work, if we collect together the most important toxicological observations which have been published as regards the most important of these anaesthetics. I. Amylene. C5H10. This hydrocarbon, in which the carbon is not fully saturated, is distinguished by its peculiar smell, somewhat resembling the odor of garlic. Its boiling point is 35° Centigrade = 95° Fahren- heit ; its specific gravity, 0.65. It was long ago repeatedly tried as an anaesthetic in surgical operations, at the recommendation of Dr. Snow. Very numerous experiments on both men and animals have confirmed the powerful anaesthetic effects of this substance, without our being able to discover that its effects differ in any very essential manner from those of similar sub- stances. Nor can we find that it possesses any peculiar advan- tages, although it has been lauded in extravagant terms. That it is not any safer than chloroform was shown by the occurrence of two fatal cases very shortly after Snow had recommended its use. These cases were witnessed by Snow himself. The death was by narcosis, and the symptoms were similar to those of death by chloroform. II. Bichloride of methylene. CH3C12. This substance, which is not only very like, but closely allied, to chloroform in its composition, has been particularly recom- mended by Richardson and Junker. Except in England, where it was a good deal used in several hospitals, it does not appear to have found much favor with the medical public. Richardson has lately recommended a mixture of bichloride of methylene and sulphuric ether, under the name of methylether, as a very useful anaesthetic. Three cases of death from the former and 454 BOEHM. —POISONS. one case of death from the latter secure for these substances a place amongst poisons. There is, however, no essential differ- ence between their effects and the mode of death to which they lead and those of chloroform. We must, therefore, as before, refer to that chapter for details. III. Bichloride of ethylidene. C2H4C12. (Boiling point 60° to 62° C.=140° to 143.6° F.) This substance was recommended by Snow and Liebreich as an anaesthetic, and from the favorable accounts of several au- thors it would appear that the results of its use have generally been fortunate. Yet already one death has occurred from its use in one of the Berlin clinics. We must refer to special works for information as regards the differences between these substances and chloroform in their effects. As regards their poisonous properties we consider ourselves justified in saying that no important difference is yet known.' No cases of poisoning have been hitherto reported from the use of nitrite of amyl or of croton chloral. Interesting as these medicines are, we are therefore compelled to pass them over without further notice. IV. Nitrous oxide (laughing gas). Although the narcotic effects of this gas were discovered by Sir Humphrey Davy at the beginning of this century, and although they were observed by numerous authors who suc- ceeded him, it was first introduced into dental practice as an anaesthetic some thirty years ago in North America. Of late years its use for this purpose by dentists has attained to very large proportions in Europe, and general experience is unanimous in the verdict, that for operations which only last a very short time, such as the extraction of teeth, it is a very serviceable, and if properly employed, a very safe means of benumbing pain. The mode of action of this gas was first placed in its proper light, and confirmed by experiments, by L. Hermann, viz., that when breathed without admixture of atmospheric air or oxygen, like hydrogen, and other indifferent gaseous bodies, it kills by suffocation (or simple deficiency of oxygen). Inhaled in a mix- 1 Compare, as regards this, the references of Husemann in the Jahresbericht iiber die Fortschritte der Medicin of Virchow and Hirsch. 1865-74. ANaESTHETICS.—NITROUS OXIDE. 455 ture in the proportion of four of nitrous oxide to one of oxygen it produces in human beings a cheerful narcosis, like inebriation by alcohol, which quickly disappears when the in- halation of the gas is discontinued. Consciousness and sensa- tion are never perfectly abolished during this condition. There can, therefore, be no doubt that nitrous oxide, like other anaes- thetics (chloroform, ether, etc.), affects the functions of the cere- brum. In animals this mixture of gases seems to have no effect. The mode of using this gas by dentists differs from that in which other anaesthetics are used, because the access of the oxy- gen of the atmosphere is prevented, and only the pure unmixed nitrous oxide is used as the anaesthetic. In consequence of this the narcotic effects of the gas are combined with the first stage of suffocation, so that deep narcosis speedily occurs, during which operations which only last a few seconds can be performed quite painlessly. It follows, as a matter of course, from what has been said, that if the experiment be prolonged to a period of a few minutes, death by suffocation must necessarily result. As loss of consciousness and anaesthesia also occur in the first stages of suffocation, without breathing in any narcotic gas, it is some- what doubtful how far the gas participates in the effect, when used in dental practice in the manner described. A narcosis which greatly resembles this can be produced by the inhalation of hydrogen whilst the atmospheric air is simultaneously ex- cluded. The enormous number of teeth extracted at the present time by the aid of this gas, without any accident, would seem to show that there is no very great danger in it. But some few fatal cases which have occurred, either during or after the narcosis, show that it is not absolutely devoid of danger. These, however, appear to be simply and solely due to suffocation, and the gas itself appears innocent. This is not the place to lay down rules for the safe use of this gas ; moreover, it appears very doubtful whether the unfortunate cases ought to be reckoned as cases of poisoning at all. The indications for treatment in such cases are precisely those which are laid down in surgical manuals for the treatment of asphyxia from other causes. 456 BOEHM. —POISONS. CHAPTER VI. POISONING BY CARBONIC OXIDE, AND BY THOSE GASEOUS MIX- TURES IX WHICH CARBONIC OXIDE IS THE ESSENTIAL INGRE- DIENT (AS POISONING BY THE VAPOR OF CHARCOAL AND POISONING BY' COAL-GAS USED FOR LIGHTING) Carbonic oxide plays a prominent part amongst poisonous gases. It is a colorless, and almost odorless gas, which is very slightly soluble in water, and burns in the air with a pale bluish flame. It is easily generated when coals or charcoal are burnt with insufficient access of air, and besides this, it is an ingredient in gas used for illumination.1 In most cases this poison is received into the system by the organs of respiration; from the surface of the lungs it diffuses itself into the capillaries. Whether carbonic oxide may gain access to the blood in other more indirect Avays, seems doubtful, and there are no trust- worthy experiments on this point. Friedberg ! has contradicted Husemann's 3 assertion that Carminati had proved the possibility of the absorption of the vapor of charcoal through the surface of the body. Carminati's experiments did not relate to carbonic oxide at all, but to the vapor of sulphur (Schwefeldampf). Nor is anything known accurately as to the ways in which carbonic oxide is eliminated from the system. On this account the manner in which this poison acts upon the system, and especially on the blood, deserves especial study. This gas is not easily soluble in blood, though more so in this fluid than in water, which will only dissolve about j\ of its volume. In regard to its solubility in blood it is far inferior to carbon dioxide, and to hydrogen sulphide. Claude Bernard4 found that blood could absorb 9.4 volumes per cent, of carbonic oxide, and confirms Nysten's5 assertion, that large quantities of this gas, 1 See also the chapter on Etiology. 2 Die Vergiftung durch Kohlendunst. Berlin. 1866. S. 79. 3 Handbuch der Toxikologie. S. 656. 4 LeQons sur les effets des substances toxiques. p. 157. 5 Recherches de physiologie et de chimie pathologiques. Paris. 1811. CARBONIC OXIDE. 457 injected suddenly into the veins of an animal, brought about death mechanically by gaseous embolism, which does not hap- pen after injection of carbon dioxide or sulphide of hydrogen in gaseous form. Small as the quantity of this gas absorbed by the blood may be, it suffices to bring about very extensive and serious changes in its properties. The researches of Claude Bernard (loc. cit.), of Lothar Meyer,1 and Hoppe-Seyler3 have established the fact that carbonic oxide displaces oxygen from the blood, and enters into combination with the coloring matter of the blood in such a way as to render this incapable of absorbing more oxygen. The out- ward sign of this change is manifested by a peculiar, bright cherry-red coloration of the arterial as well as venous blood; whilst in the spectrum of blood containing carbonic oxide the two usual bands of oxyhemoglobin are replaced by two others, which appear nearer to the violet end of the spectrum, and these carbonic oxide bands exhibit the special character of not vanish- ing on the addition of reducing agents, as those of oxyhaemo- globin do. The compound of haemoglobin with carbonic oxide is crystallizable just like oxyhaemoglobin. It is more solid than this, and is less easily evaporated in vacuo. However, it can be decomposed by passing other gases through the blood and also by the use of the air-pump, just like oxyhemoglobin; so that we cannot help considering the two compounds as very analo- gous one to the other.3 One especial result of these investiga- tions is to show that carbonic oxide combines with haemoglobin just in the same volumetric proportions as oxygen does. It seems almost unnecessary to try to prove that this relation of carbonic oxide to the blood, which equally occurs in the living body, must to a very great extent explain its poisonous proper- ties. It makes the further reception of oxygen, and therefore life itself, impossible, and so much the more as, owing to the stability of the compound, the whole mass of the blood very speedily becomes robbed of its vital properties, provided only 1 De Sanguine oxydo-carbonico infecto. Inaug.-Dissert. Breslau. 1858. 2 Virchow's Archiv. Bd. 11. 1857. 3 Consult, on this, Zuntz, Pflueger's Archiv, V.; Donders, ibid.; and Podolinski, ibid. VI. 458 BOEH M. — POISONS. that the poison is present in sufficient quantities in the medium respired. Notwithstanding this, there is by no means such una- nimity on this point amongst those who have written on the sub- ject as we might expect, a priori. Whilst one set considers that the symptoms of poisoning by carbonic oxide are perfectly explained by the above theory, and regards the whole symptoms as essentially a form of suffocation produced by want of oxygen (Claude Bernard [loc. cit.J, Hoppe-Seyler [loc. cit,], Pokrowsky,1 Friedberg2), others insist most strongly on disturbances in the circulation (atony of the muscular coat of the blood-vessels), which must be considered as a result of poisoning by carbonic oxide, not dependent on its power of robbing the blood of oxy- gen (Klebs3). They consider that this poison acts like a narcotic on the organs of the central nervous system (Siebenhaar and Lehmann"). Pokrowsky has endeavored to establish the identity of poisoning by carbonic oxide with other forms of suffocation (breathing of nitrogen, hydrogen, carbonic acid, and mechanical occlusion of the air-passages) by a careful physiological anal- ysis of the symptoms. The results of this agree essentially with those of an inde- pendent inquiry of the same kind made by Traube,3 and founded on experiments. Indeed, the results of this inquiry are a most evident agreement in the physiologi- cal effects of the various modes of suffocation. Although we may not always agree in every minute point with Pokrowsky's arguments, yet his conclusions are undoubt- edly justified by Traube's experiments. Pokrowsky's experiments show the follow- ing results: That after the first breathing of a medium poisoned with carbonic oxide, the blood-pressure, which was first considerably increased, soon sinks consid- erably with a simultaneous considerable retardation or slowing of the pulse. This second phase in the phenomena of the circulation in poisoning by carbonic oxide has all the characters of a blood-pressure and pulse-curve due to peripheral irrita- tion of the vagus. This stage is succeeded by a third, in -which a still lower grade of blood-pressure, and a shallow, but more frequent, pulse are met with. Unless artificial respiration is resorted to in this stage, death follows with constant increase of the symptoms last named up to the moment of death. Division of the vagus nerves in the second stage completely annuls it, but under certain conditions only retards it, when the operation has been done before the poisoning ; as for instance, 1 Archiv f. Anat. und Physiol. 1866. * Die Vergiftung durch Kohlendunst. Berlin. 1866. 3 Virchow's Archiv. Bd. XXXII. 4 Die Kohlendunstvergiftung. Dresden. 1858. b Gesammelte Beitrage zur Pathologie und Physiologic 1. Band. CARBONIC OXIDE. 459 when the attempt at poisoning has been repeated several times in rapid succession, or when the animal is already suffering severe dyspnoea as the result of the previous section of the vagus. In the third stage (of low blood-pressure, with small and fre- quent pulse) irritation of the medulla oblongata, or of the cervical cord, is fol- lowed, as a rule, by a considerable increase in the blood-pressure. In the present state of physiological opinion on the circulation, these views of Pokrowsky, which are established by a long series of experiments, all pointing in one direction, are explained in the simplest manner by considering them as simple results of the deficiency of oxygen. This at first causes a transient increase in the blood-pressure, by irritation of the vaso-motor centres, which is succeeded by a period of central (and perhaps peripheral also) irritation of the vagus, in its turn succeeded by paralysis of the vaso-motor centres. All these events are also seen to occur if we stop the aeration of the blood in any other way, provided it be not done too suddenly. Pokrowsky differs from this conclusion, inasmueh as he believes the first as well as the last-named stages to be dependent on excitement or excitability of an excito-motor centre for the heart, situate in the medulla oblongata. He does not hold our view of the case to be valid, because he sees no increase of pressure follow compression of the aorta in the third stage. On this account he admits a weakening of the action of the heart, which may be temporarily removed by irritation of this centre in the medulla. We have felt obliged to differ from him, because the existence of this excito-motor centre in the medulla, which, it is well known, von Bezold admitted in his day, is at the present moment more than doubtful. Pokrowsky also seems to us to be decidedly wrong in believing that contrac- tion of the (small) arteries coincides with the sinking of the (blood-)pressure; and still more so when he brings this forward as an argument against Klebs's theory of poisoning by carbonic oxide, for this is well known to be based on atony of the arteries. The effects previously quoted from his paper on irritation of the cervical cord, show clearly that P. has probably deceived himself in this matter, and observations on the calibre of the vessels of the mesentery or other parts, with or without a microscope, are at present not very reliable modes of physiological inves- tigation. Klebs, indeed, despairs of any generally acceptable view of the true nature of carbonic-oxide poisoning, but he pronounces in no doubtful terms against the view of the symptoms given above ; and he considers the atony of the vessels as a sort of middle term between the poisoning and the asphyxia which finally suc- ceeds it. But all controversy apart, there is atony of the vessels, though it may not be very great, in all stages of the whole affair. Klebs considers the want of suffocative spasms as a sufficient reason for not assigning the symptoms in this kind of poisoning to mere deficiency of oxygen. And he draws particular attention to the general occurrence of sopor in poisoning by carbonic oxide—a symptom not noted in simple abstraction of oxygen. Lastly, whilst he will not assert the absolute impossibility of the two conditions being alike, he thinks that at least their identity is not proved. Whilst agreeing with him in this last opinion, we cannot accept all the arguments and experiments on which he founds it. As regards the absence of 460 BOEHM.—POISONS. convulsions or spasms, Klebs contradicts almost all who have written on the sub- ject. Though this symptom may be wanting or imperfectly developed in some instances, it is present in an overwhelming majority of the cases, and even some of Klebs's cases seem not quite free from doubt on this point. Nor can we agree with Klebs in the importance he attributes to sopor. Against this doubtful symptom, we have to set the general agreement in the disorders of the circulation produced both in carbonic-oxide poisoning, and also in the various forms of suffocation. We must agree with Klebs as to the significance of the vascular paresis, but not in attrib- uting the comatose condition met with in poisoning by carbonic oxide to direct blood-pressure on the cortical surface of the brain produced by the vascular dilata- tion. Simple reflection will show us that, in every paresis of the vaso-motor cen- tres, there must result a relative anaemia of the central organs of the nervous system; because whilst the efflux through the veins is unhindered, the afflux through the arteries is diminished; and since the chief mass of the blood is circulating through the great vascular domain of the abdominal vessels, it is clear that the mean blood- pressure is diminished. Vascular paresis is therefore more likely to cause anaemia than hyperaemia of the cerebral vessels. It is only one link in the chain of the symptoms of poisoning by carbonic oxide, and necessarily results from the grad- ually decreasing vital excitability of the organs of the central nervous system through the failure of oxygen. The modern classification of carbonic oxide as a narcotic poison, warmly advo- cated by Siebenhaar and Lehmann, need not detain us, because no fresh facts or explanations are given. The expression, " narcosis," is a vague term for a number of things which differ widely as regards their physiological basis. There are, how- ever, a few facts not mentioned, which seem to contradict any special action of carbonic oxide on the nervous system. Frogs do not die much more quickly in this gas than they do in other indifferent gaseous mixtures deprived of oxygen ; and invertebrate animals, which do not possess blood containing oxyhsemoglobin, are not all affected by it.1 The nerves and muscles of the frog, and the heart of the same animal, are not at all affected by this gas as regards their vital properties. The explanation of the various symptoms in poisoning by carbonic oxide will be dealt with, as far as practicable, in the section relating to the Symptomatology. It is not possible, in the present state of our knowledge, to definitely decide for or against either of these theories of poison- ing by carbonic oxide. However numerous the facts which tend to make us accept the tlieory of a pure toxaemic action of this gas, we must not forget that there are others which cannot be reconciled with this view. It has very properly been insisted on that, even in the corpses of men killed by carbonic oxide, oxygen- ated haemoglobin can be detected in the blood by the spectro- 1 See Pokrowsky, loc. cit. CARBONIC OXIDE. 461 scope; and we are therefore still uncertain how much oxygen must be Avithdrawn from the system before toxic symptoms are induced, or whether, in a given case, the actual deprivation or removal of oxygen has been sufficient to explain the symptoms in their entirety. The remarkable immunity of some persons as regards this form of poisoning would seem to support the view that the abstraction of oxygen is not an essential factor in the action of carbonic oxide on the nervous system. But it must be remembered that some people can bear to be deprived of oxygen much better than others, whilst we have no very satisfactory examples of an analogous immunity as regards any specific nerve-poison. Experiments made by injection of blood saturated with car- bonic oxide into the circulation of animals, such as those of Claude Bernard, Klebs, and Traube, have not hitherto furnished any certain results. As oxygen is not withdrawn in these experi- ments, and yet symptoms of poisoning occur, we might conclude that this was in favor of a direct toxic action of carbonic oxide. But the quantity which can thus be introduced is, after all, but little, and the symptoms produced have not amounted to much more than slight dyspnoea. The antagonism which, as Klebs asserts, exists between carbonic oxide and ergotin, might be held a weighty argument against the toxaemic and in favor of the spe- cific poisonous action of carbonic oxide. For ergotin cannot sup- ply the deficient oxygen, and if, notwithstanding, it is really antagonistic, Klebs's theory would seem to gain support. But, alas! this action of ergotin seems not sufficiently proved. Klebs's report on these ergotin experiments gives no figures for the mean blood-pressure before and after the poisoning by carbonic oxide, and after the ergotin injection, so that the particular action of the ergotin on the diminished blood-pressure cannot be estimated. And again, we are left in doubt by this report whether the administration of the gas was continued or broken off after the injection of the ergotin. A true antagonism could only be admitted if the poisonous symptoms decreased in spite of continued inhalation of the carbonic oxide. In all the cases in which the carbonic oxide was removed, we are led to doubt whether the access of oxygen, and not the ergotin, proved the 462 BOEHM.—POISONS. antidote, or at least did the good which is recorded. Lastly, the sequelae of carbonic oxide poisoning, so often met with, require comparison with the facts which are so difficult to recon- cile with the simple abstraction of oxygen. Further experi- ments may be needed to remove the difficulties which exist in the way of either theory. In the meanwhile, therefore, our judg- ment must be suspended. Chemically pure carbonic oxide is very seldom the means of poisoning. In general, this poison is mixed with other, in part indifferent, in part equally injurious gases, so that, however strongly inclined, we can scarcely regard the cases as simple cases of poisoning by carbonic oxide. Yet multiplied experiences have taught us that the danger of these mixtures depends un- doubtedly on the carbonic oxide present, and that, apart from this, the gaseous mixtures produce but very trifling symptoms. We may, therefore, practically disregard the admixtures. The most important compound of this kind is the vapor of charcoal, which contains, in addition to carbonic oxide, large quantities of carbonic acid, and some traces of the. carbides of hydrogen. Any certain estimate of the relative quantities of these gases in the vapor of charcoal is not possible. According to Eulenberg, most of the analyses have given about 2.5 per cent, of carbonic oxide and 24.6 per cent, of carbonic acid. It is easy to understand that in general there is also an admixture of atmospheric air. Sometimes hydrogen sulphide and combus- tible gases are also mixed Avith it. The second mixed gas of which carbonic oxide forms the most important constituent is the coal-gas used for illuminating purposes. We must, therefore, consider cases of poisoning by the vapor of charcoal and those due to lighting-gas. The special etiology of poisoning by the vapors of charcoal almost always depends on the imperfect combustion of materials rich in carbon (wood, charcoal, anthracite, coke, etc.), and the commonest cases of all are those due to defective heating appa- ratus (stoves, braziers, etc.). When the stove-pipes, destined to carry away the products of combustion, become choked with soot, or when the valves are closed, the gases generated by com- bustion can only accumulate in the space which is being warmed, CARBONIC OXIDE. 463 and those persons who remain in the place where the stove is are poisoned; the more easily the smaller the room, or the more defective the ventilation. An opinion formerly prevailed that the poisonous gas is most abundant in the lower portions of the room, just above the floor, but it is now known that the poison- ous mixture of gases is most dense, as might be expected, close to the burning materials. But they may be capable of doing a great deal of harm at a very considerable distance from the place where they are generated. Cases are on record in which the vapor of charcoal has dif- fused itself through several large rooms, or through communi- cating flues, into stories quite separate from the floor on which it was generated. Even in the open air, in the immediate vicinity of charcoal ovens, there may be very dense accumulations of the vapor. There are several cases in which the smouldering of beams under the floor or in walls, from accidental combustion, has caused danger in dwelling-rooms from the vapor produced. The unskilful use of braziers and warming-pans, and the like circumstances, naturally belong to the same category and need not detain us. Fires in mines and other underground places (tunnels, etc.), and blasting operations, are especially dangerous on account of the defective circulation of air, and these gener- ally afford numerous victims. What has been called the " Sapper's and Miner's disease " (Minenkrankheit) has been attributed to carbonic oxide poisoning. According to recent investigations by Polleck,1 who took advantage of a siege in the fortress of Neisse to examine the constitution of the gases generated in mines by the explosion of gunpowder, the percentage of carbonic oxide is not any considerable quantity except at the begin- ning of the blasting operations, and is gradually diminished in consequence of a variety of causes, which need not be detailed here. In unison with this the sappers and miners suffered most severely at the beginning of these operations, and their sufferings gradually decreased, both in severity and in number. In the meanwhile, it is by no means certain that these conditions are identical with poisoning by car- bonic oxide. The majority of cases of poisoning by carbonic oxide are due 1 Die chemische Natur der Minengase und ihre Beziehungzur Minenkrankheit. Ber- lin. 1867. The Chemical Composition of the Gases in Mines, and their Relation to the Miner's Disease. 404 BOEHM.—POISONS. most certainly to want of due caution, or to accident; yet there are many recorded (rases in which the poison has been used for suicidal purposes, and a few in which it has served the purposes of murderers. In Germany suicides by carbonic oxide are very seldom observed, while in France this mode of suicide is exces- sively common.1 Poisoning by coa.-gas used for lighting is far more rare. The quantity of carbonic oxide required to kill is not easy to estimate; and the most accurate estimates which are recorded refer exclusively to the lower animals ; we therefore think it unnecessary to reproduce them.2 The question as to individual predisposition, or sensitiveness to carbonic oxide, has been pre- viously mentioned. It has been observed, in some cases, that different persons, exposed to the same mixture or quantity of the gas, have been variously affected; some even appearing to exhibit a perfect immunity. As regards this fact, which requires more precise confirmation, we can give no explanation. Klebs attributes it to different conditions of the heart in different peo- ple, but this is not easy to demonstrate. It is quite certain that children succumb rapidly to the action of this poison, which may perhaps be due to the great activity of the respiratory process in young people. There is a pretty general agreement amongst authors as to the symptoms produced by carbonic oxide in human beings. The first subjective symptom which occurs after breathing the poison is a burning feeling in the skin of the face (Klebs3), quickly followed by giddiness and headache, which gradually becomes more intense; the chief site of this headache is in the temples. Experimentalists and those poisoned agree in this. This headache or pain is generally associated with a subjective feeling of strong pulsation in the temporal arteries. Occasion- ally, even in this prodromal stage, we get feelings of nausea, and of oppression in the stomach and in the precordial region. Very often, though not invariably, these are associated with a variety of subjective sensations, as motes dancing about (muscae voli- 1 As regards the statistics of this consult Husemann's Toxikologie. pp. 60, 654. 2 See Husemann's Supplement, loc. cit. p. 101. 3 Loc. cit. p. 469. CARBONIC OXIDE. 465 tantes), noises in the ears, and the like, symptoms which indi- cate, to a certain extent, the severance of the sensorium from the domain of reality, and the transition to perfect loss of conscious- ness. The psychical condition which precedes the latter is some- times a distress of mind, full of agonizing tortures, sometimes a sort of pleasant and ecstatic feeling ; but the former appears to be the rule. The access of insensibility is either a sudden with- drawal from consciousness, like a stroke ; or it is preceded by pronounced phenomena of great discomfort—anxiety, nausea, and excitement—which often lead the poisoned persons to make an effort to leave the poisonous atmosphere in which they find themselves, or to try to get air by opening the windows, etc. Very often the insensibility attacks them during this very effort, so that the poisoned person falls down half way to the window or door, and lies there unconscious. At this stage all perception and consciousness of anything further are lost, so that we can- not look to the victims for any further account of themselves. The subjective symptoms which are noted in cases of recovery or restoration to consciousness are more varied and less charac- teristic. The most marked is a feeling of general weakness and extreme .fatigue, which often lasts for several days, and accu- rately corresponds to the objective symptoms of this stage. Vague headaches, a want of clear conceptions, and genera' obscurity of the mental faculties are associated with this, as they are with many other conditions met with in a variety of other diseases. Eccentric pains in the extremities, and disorders of cutaneous sensibility are especially marked in those cases where the poisoning gives rise to profound functional mischief of the spinal cord. In cases which end fatally, the victims either never wake from the deep coma (sopor), or their awakening is only transitory and imperfect, and soon gives place to fresh attacks of insensibility, and more or less suddenly leads to death. The objective phenomena observed in cases of poisoning by carbonic oxide are very numerous and varied, and may be conveniently grouped, according to the organs affected, somewhat as follows : The external surface or skin of those poisoned shows much congestion and redness at an early stage, particularly in the VOL. XVII.—30 466 BOEHM.—POISONS. face; the ocular conjunctivae are injected, but the diameter of the pupils is not much affected. The color of the mucous membranes accessible to sight usually remains for a long while of a lively red. In the later comatose stages the skin is for the most part pale, and only becomes livid and cyanotic towards the end of life, in consequence of the disordered circulation. Many observers have also noted, during the poisoning itself, and in the sequelae which are so often met with in these cases, a great variety of cutaneous affections, from simple rubeola, or the formation of blisters, to extensive gangrene and bedsores—symptoms which probably depend on the vaso-motor paresis. Herpetic eruptions, both simple herpes labial is and the so-called herpes zoster, have been observed as consequences of poisoning by carbonic oxide (Leudetl). The respiratory functions are not always very prominently affected in carbonic oxide poisoning; and this is no doubt one reason why so many authors have been led to doubt the theory of a simple suffocative action of the poison. The cases in Avhich early dyspnoea is succeeded by asphyxic convulsions, thus plainly indicating suffocation, are certainly far from common. It is far more general for the initial stages of dyspnoea to be succeeded by a comatose condition, in which sometimes it would appear as if there were no hindrance to respiration, which goes on in a regular rhythm, death occurring without any marked convulsions. But, on the other hand, there is no doubt that the rule is for convulsions to occur in the final stages of poisoning by carbonic oxide. Siebenhaar and Lehmanns point out that symptoms of dyspnoea do not gene- rally occur until after the general paresis and weakening of the cardiac activity; and they believe accordingly that this renders the suffocative theory of the action of the poison untenable. On the other hand, these authors sketch so typical a pic- ture of death by suffocation, that it only wants to be pointed out in order to convince as to the possibility of this emanation.3 We must indeed not expect in ] Archives generale?. VI. Ser. torn. 5. Mai 1865. p. 513. 2 Loc. cit. p. 41. 3 We quote a small portion verbatim: " Towards the end of the attack, the breath- ing is in almost all cases somewhat quickened, and even seems to be tolerably ener- getic, and as if accomplished with great exertion (sic); but in general this rapidity of the CARBONIC OXIDE. 467 these cases such violent {lit. stormy) symptoms as occur after forcible ligature of the throat (strangulation), or after similar modes of suffocation. The gradual im- poverishment of the blood as regards oxygen will be likely to bring about a sim- ilar gradual change in the functions of the respiratory centres. All the observations made, both on men and in animals, show that the inspirations become marked by pauses which gradually grow longer, and thereby the respirations gradually acquire a forced and truly dyspnoeal character, whilst, at least in the early stages, respiration is temporarily accelerated, and there is at the same time a feeling of precordial anxiety. But besides these abnormities of respiration dependent on the nerve-centres, we sometimes get, particularly in true char- coal-vapor poisoning, palpable changes in the organs of respira- tion, which occur under the form of either acute bronchitis, hamoptysis, or pneumonia, with or without pleurisy. Klebs (loc. cit.) considers these complications, often seen by him, as accidental; whilst Friedberg (loc. cit.) and others consider them to be directly dependent on the poisoning. They attribute them in part to the mixture of gases, which act as direct irritants to the lungs, etc., and partly to the disordered circulation brought about by the carbonic oxide. We must leave this controversy to be settled by more precise observations. The objective demonstrable disorders of the circulatory sys- tem are confined to not very pregnant and very variable changes in the arterial pulse, which is full and quickened for a little Avhile, but, later on, becomes gradually less powerful, and in the stage of coma can scarcely be felt. The explanation of these phenomena will be found, in part, in what has before been said as to the physiological effects. The temperature of the body is considerably decreased in poisoning by carbonic oxide (about 2° to 2.5° C. = 3.6° to 4.5° F., Pokrowski, loc. cit., Klebs, loc. cit.). in- and expiration soon passes away; the excitement gives place again to an equally tranquil condition, and the breathing in particular become less rapid and more super- ficial, whilst the general paresis and the condition of torpor increase ; at a later stage again, there are constantly increasing pauses in the breathing, between which, now and then, some strong respiratory movements become visible, and finally, there follows, after one such inspiration, that long pause which is succeeded by death, imperceptibly and without any visible spasms or convulsions." 468 BOEHM.—POISONS. The disorders of the digestive organs are quite subordinate to the other symptoms ; as a rule, there is more or less vomiting in the early stage. Extensive inflammation of the mucous mem- brane of the digestive tract, with a tendency to necrotic ulcera- tion, has been noted in isolated cases by Ziemssen and Thom- son. ' The occurrence of diabetes mellitus is of especial interest. It is a symptom now seldom wanting in cases of carbonic oxide poisoning, since first pointed out by Friedberg (loc. cit.), though as yet its real import and connection with the poisoning has not been discovered. Senff3 has endeavored, in a searching investigation of the pathogenesis of car- bonic oxide diabetes, to establish and demonstrate that the excretion of sugar in the urine does not depend on inhibited oxygenation, since sugar injected directly into the blood of animals poisoned with carbonic oxide is burnt up, and does not pass into the urine. He has further shown that if the access of arterial blood to the liver is hindered by the ligature of the arteries concerned, there is no diabetes in these cases of poisoning by carbonic oxide; so that we may conclude with great probability that an excess of sugar is formed in the liver in this mode of poisoning. That it is really the glycogen of the liver which is concerned in this matter is also shown by the fact that the diabetes is generally absent in fasting animals, in whom it is admitted that the liver is almost entirely free from glycogen. For the most part the diabetes in poisoning by carbonic oxide is associated with albuminuria. Both these symptoms last for a feAv days only at most, and disappear with the other symptoms of poisoning. Lastly, as regards the palpable disorders of the nervous sys- tem, these are limited to sometimes local, sometimes general anasthesia of the cutaneous surface and paralysis of the volun- tary muscles; the latter frequently lasts much longer than the other symptoms, and may be complicated with atrophy of the muscles concerned.3 Paralysis of the involuntary muscles of the bladder and of the bowels is often mentioned in the cases recorded. The course and duration of poisoning by carbonic oxide natu- 1 See Friedberg, loc. cit. 2 Ueber den Diabetes bei Kohlenoxydvergif tung. Inaug.-Dissert. Dorpat. 1869. 3 Consult Friedberg, loc. cit. p. 123. History of a case by Schwartz. CARBONIC OXIDE. 469 rally depend chiefly on the duration and intensity of the action of the poison. The great frequency of fatal cases depends largely on the fact that the poison almost always, except per- haps in the case of suicides, attacks persons who are asleep, and in the night-time, so that any intervention, which would have the effect of saving their lives, if timely, does not and cannot usually occur until some hours at least have elapsed, perhaps not till next day. If carbonic oxide and the gases usually asso- ciated with it are allowed to operate persistently, they bring about a fatal termination in a few hours. If the poisoned per- sons are more or less quickly removed from the injurious vapors, either recovery takes place after a little while, with gradual van- ishing of the symptoms, or death occurs in a day or two, various symptoms persisting in the meantime. Carbonic oxide cannot therefore be reckoned amongst the very rapidly killing poisons like prussic acid. The corpses of those dying from carbonic oxide poisoning show a remarkable resistance to putrefaction, and exhibit outwardly certain characteristic signs of the mode of death. Amongst these are broad and extensive irregularly outlined bright-red spots or patches on the anterior surface of the whole body, the color depending on the impregnation of the blood with carbonic oxide. Sometimes a darker or more violet hue is seen, particu- larly if the carbonic oxide has been already converted into car- bonic acid, or if the gaseous mixture contained an overwhelming proportion of the latter gas. A similar rose-red coloration is often met with in the internal organs, in the muscles and serous membranes (peritoneal coat of the intestines). The changes in the blood itself are just as little constant, the characteristic cherry-red being often replaced by the commoner dark colora- tion of the blood often seen in corpses. The question whether these variations depend on more or less of the carbonic oxide being present does not seem settled as yet. The demonstration of carbonic oxide in the blood itself is, hoAvever, always an easy matter, whilst the corpse is still fresh, if Hoppe-Seyler's method be adopted. For the details of this we must refer to manuals of medical jurisprudence, and to the special literature of the subject. 470 BOEHM. —POISONS. Next to these phenomena, authors unanimously insist on the great fulness of blood met with in the parenchymatous organs and other viscera, and on the extreme injection of all the capil- lary vessels brought about by the general vascular paresis. Klebs 1 observed this most particularly in the meninges and cor- tical portions of the brain ; and found a varicose condition of the small arteries in the membranes, which usually run in a straight course in young subjects. The muscles and glandular organs (liver, kidneys, glands of stomach) are often found in a condition of advanced fatty degeneration, in consequence of molecular degeneration of the cellular elements, as has been noted also in various other kinds of poisoning (phosphorus, arsenic, etc.). This has been confirmed lately. The glandular organs mentioned often show increase of bulk (parenchymatous swelling). Ecchymoses are found in the pleurae, peritoneum, pericar- dium, and meninges. These are probably connected closely with fatty degeneration of the coats of the vessels. This parenchy- matous degeneration sometimes goes on to necrotic destruction of tissues. The corpse then exhibits patches of softening (Er- weichungsherde) in the brain, kidneys, and muscles. In the lungs, besides emphysema of the margins (no doubt due to the dyspnoea during life), there are various inflammatory conditions, which need not be discussed here in detail, since they are met with in other cases (of disease), and are elsewhere described. The contents of the stomach are often found in the trachea and bronchi; and this depends, as Friedberg" believes, not always on a post-mortem overflow from the stomach, but very often on vomiting during life, during which the diminished reflex sensibil- ity permits these matters to invade the air-passages unhindered. The removal of the poisoned persons out of the dangerous atmosphere must, as a matter of common sense, be the first act of our therapeutics. Generally speaking, it is best to actually move the patient into another well-ventilated room, or into the open air, but it may sometimes be necessary or even best to treat them on the spot, changing the air of the room by appropriate measures, such as opening doors and windows, etc. The further 1 Loc. cit. p. 458. 2 Loc. cit. p. 86. CARBONIC OXIDE. 471 treatment of each case must depend on the degree and stage of the poisoning. In mild cases, this change of atmosphere may suffice to ward off danger, especially if the patient breathes well, and is conscious. But if there be much dyspnoea or a comatose condition, we must resort to energetic measures. If respiration be re-established, it must be carefully watched. Artificial respi- ration must be performed when the breathing is badly done, or in abeyance. Even if this do not eliminate the carbonic oxide from the blood—because, as we have seen, the compound of carbonic oxide, etc., Avith haemoglobin is not easily got rid of— yet the induction of artificial respiration has at least this indis- putable advantage, that it may possibly excite a livelier inter- change of gases in the remainder of the blood which is still nor- mal, so that a greater quantity of oxygenated blood may reach the nervous centres. We need not enlarge on the different methods of artificial respiration. Any one of them will serve the purpose. Friedberg and Ziemssen have lately strongly recom- mended faradization of the phrenic nerve and its vicinity; a proceeding which, in any case, will prove a valuable auxiliary to artificial respiration. Air might also be blown into the larynx through a catheter or oesophageal tube. When there is much cyanosis of the mucous membranes, and very dusky hue of skin, many authors recommend venesection, and in experiments on animals Kuehne found that, if the animal only breathed more than once a minute, recovery took place when bleeding Avas done, whilst similar cases not bled died. As in other forms of asphyxia, so here also, in addition to ordinary measures, energetic stimulation of the peripheral nerves is often a very rational mode of treatment. The object is to excite respiration by acting in a reflex manner on the now weak- ened, but still living central organs of the nervous system. Such measures as sprinkling with cold water, rubbing with ice or snow, the hot iron (thermal hammer), hot shellac, etc., may be adopted, or the mucous membrane of the nose, etc., maybe irritated either mechanically or chemically (ammonia, acetic acid, etc.). When, in spite of these therapeutic efforts, the threatening symptoms persist, we are advised by Kuehne, Panum, Friedberg, Traube, and others, that recent experience is strongly in favor of a deple- 472 BOEHM.—POISONS. tory transfusion of blood. A part of the poisoned blood is first removed, and a corresponding quantity of the normal defibri- nated blood of a healthy man is substituted. Several successful cases of this kind are recorded, and there seems to be no valid argument against this proceeding. In dubious cases, Friedberg strongly recommends that this exchange of blood should be repeated more than once. The methods of transfusion will be dealt with elsewhere. As regards the use of ergotin, suggested by Klebs as an antidote, we have no practical experience up to date. Nor can we recommend it, since ergotin is not an inert substance by any means. The treatment of the complications and sequelae of carbonic oxide poisoning belongs to the domain of general therapeutics. CHAPTER VII. POISONING BY CARBONIC ACID (CARBON DIOXIDE). Although the suffocating action of concentrated carbonic acid gas has long been known, yet there has been much hesitation in calling it a "poison." Even Claude Bernard, in his " Lecons sur les effets des substances toxiques," etc., advances the opinion that this gas, innoxious in itself, can only become dangerous to ani- mal life when it becomes accumulated, in a concentrated form, in the air-passages, and thus hinders the oxygenation of the blood. These and similar views—as, for example, that carbonic acid is in itself an innocent or indifferent gas, like hydrogen or nitrogen—have been perfectly contradicted by the experiments and researches of the last ten years; so that nowadays no one doubts the poisonous character of this gas. Yet in practical toxicology carbonic acid does not play a very prominent part. The interesting results of numerous experiments, made by the first physiologists of our times on the relations of this gas to the processes of respiration, do not very greatly increase our knowledge of this matter, and indeed, as regards the peculiar toxic effects of carbonic acid, the experimental science of our CARBONIC ACID. 473 day still fails to answer the question—" In what way does this gas kill?" Since carbonic acid only causes severe symptoms in very considerable quantities, or after a relatively long dura- tion of exposure, we seldom have opportunities of observing cases of poisoning in human beings. When such cases do occur, they either kill so quickly that any accurate observation is impossible, or the symptoms in other cases are so slight and transient as not to admit of careful determination. Our pres- ent task will be limited to furnishing a brief and condensed sketch of the present state of our knowledge of the action of carbonic acid, referring for more minute and extended details to purely physiological literature. Carbonic acid is a gas at the ordinary pressure of the atmos- phere, and in the presence of carbonated salts it is very largely dissolved in watery fluids ; by the application of higher pres- sures a large quantity can be condensed or compressed into dis- tilled water. It is a weak acid, reddens litmus paper, and excites a slight, pleasant, cool, prickly or pungent sensation in mucous membranes largely supplied with nerves (such as the lips, tongue, palate, etc.). As carbonic acid is set free from its combinations with most bases by the stronger acids of the stomach, the carbonated salts must be included with the acid. Carbonic acid seems to be absorbed most rapidly from the surface of the lungs, yet a very considerable quantity passes into the blood from the stomach and intestinal canal, from the subcutaneous connective tissue, and even from the uninjured epidermis. From the blood it is returned again to the atmosphere through the lungs, with a rapidity proportioned on the one hand to the smallness of the percentage of carbonic acid in the surrounding air, and on the other hand to the intensity of the breathing process. If the quantity of carbonic acid in the air is so great as to equalize the pressure of the gas within the blood, the gas in the blood will be retained there, and may accumulate so as to produce dangerous effects, since the gas continues to be formed within as before. Hence it comes to pass that both men and animals may be poi- soned by the carbonic acid they themselves generate, provided they remain long enough in a restricted space Avithout [ade- 474 BOEHM.—POISONS. quate] ventilation, although in such cases the gradually increas- ing deficiency of oxygen plays a very important part. In the mode of its operation, carbonic acid undoubtedly deserves to be ranked with narcotic poisons. The most impor- tant elements in its operation are the effects it produces on the central nervous system. Carbonic acid, according to physiologists, is one of those irri- tants which bring about the respiratory movements by way of the medulla oblongata. Traube1 was the first to show this by experiments. Thiry's view2 indeed was that carbonic acid is the only stimulus which in normal life keeps the respiratory centres in rhythmic activity. However, Pflueger3 contradicts this view, and considers the want of oxygen to be the normal stimulus or excitor to respiration ; but admits, without reserve, that carbonic acid may also act as a stimulus. Whilst, then, small quantities of carbonic acid only excite to a regular and orderly activity of the muscles of respiration, the accumula- tion of carbonic acid in the blood causes this stimulation to be more and more intense. In this Avay we get a typical attack of dyspnoea—at the beginning of the attack quickened and forced breathing, later on spasmodic inspirations with long intervals between them, till at last the respiratory centres, through the excessive stimulation—the over-excitation—become paralyzed, and thus death occurs as in suffocation. Hermann1 remarks that this kind of respiratory paralysis, through over-stimulation of the respiratory centres, should not be identified with ordinary simple asphyxia, in which the loss of excitability of the re- spiratory centres is originally brought about by the deficiency of oxygen. It is to be regretted that hitherto no experiments of any value have been made which illustrate the action of carbonic acid in animals which are under the influence of curare, and Avhose res- piration is kept up by artificial means. We do, indeed, know that, as a rule, in poisoning by carbonic acid, respiration gener- ally ceases before the heart stops beating. But since, from the 1 Gesammelte Abhandlungen. I. 2 Quoted by Traube. s Pflueger's Archiv. I. ' Experimental. Toxikologie. CARBONIC ACID. 475 moment respiration comes to a stand-still, the poisonous action of carbonic acid is complicated with deficiency of oxygen, we do not know the precise share of carbonic acid in the production of the cardiac paresis. Castell1 and Schiffer's2 experiments have shown that the activity of the frog's heart is only temporarily depressed by carbonic acid, provided the exposure is not too protracted; indeed the activity is sometimes temporarily increased. If the circulation is carefully watched in mammals poisoned with carbonic acid, the appearances are the same as in poisoning brought about by common suffocation (carbon compounds, de- ficiency of oxygen). The symptoms consist in retardation or sloAving of the pulse, and, at the beginning, in a very considerable elevation of the arterial blood-pressure. In later stages this is again suddenly depressed. Traube considers that the slowing of the pulse depends on a central irritation of the vagus—the vary- ing levels of the blood-pressure are brought about by irritation and perhaps paralysis of the vascular nerves. But the locality of vaso-motor stimulation is not yet accurately determined. Traube's opinion that the stimulation occurs in the vaso-motor centre of the medulla oblongata seems contradicted by the fact that this increase of blood-pressure occurs in animals whose cer- vical cord has been cut across or divided before the poisoning. A great many symptoms show that carbonic acid affects the functions of other nerve-centres. These have been verified in both men and animals during the narcosis induced by carbonic acid. Its action on the cerebrum is shown sometimes by men falling into a condition resembling the drunkenness of "jolly topers," with cheerful garrulity and pleasant hallucinations, Avhilst the occasional occurrence of tetanic convulsions in ani- mals indicates that the spinal cord becomes affected. Carbonic acid is ranked with those poisons to whose toxic action the system becomes gradually accustomed (so-called "law of tolerance"), because it has been observed that people who remain in air rich in carbonic acid gradually become less sensi- tive to the action of this injurious agent. and '' Quoted by Hermann, Exper. Toxikol. 476 BOEHM.—POISONS. The local effects of carbonic acid are, it would seem most probable, the consequences of direct irritation or stimulation of the nerves of the part to which it has been applied. The red- dening of the skin, the feeling of warmth, the total local anaes- thesia which finally occurs, and the increased activity of the secreting organs (sweat-glands, salivary glands) can all be ex- plained on this hypothesis. The circumstances which give rise to poisoning by carbonic acid are very numerous and varied. There are many localities in which this poisonous gas escapes forcibly from the surface of the soil, and accumulates either in caverns and grottoes, or sometimes fills the whole of a valley in such dense quantities as to cause both men and animals who come there to succumb at once to its influence. Amongst such places are the well-known Or otto del Cane, or Dog's Cavern, of Pozzuoli, near Naples, the Lake of Laach, in Switzerland, and its vicinity, and others near Marienbad and Pyrmont, the poison- valley of Java, and other localities, more particularly in the neighborhood of volcanoes.' Large quantities of carbonic acid may be found in charcoal works (in dull weather, fogs, etc.), mines, deep wells, wine and beer cellars, in which the liquors named undergo fermentation, in vats, cellars, and in small, badly- ventilated rooms and houses where many men live together, or remain long in one room. It has also been mentioned under car- bonic oxide that carbonic acid is one of the products of combus- tion. In all the cases mentioned the poison is breathed in or inhaled by the air-passages. It is far less usual to meet with cases of poisoning due to the ingestion of beverages rich in car- bonic acid (sparkling wines, soda-water, etc.) or through the medicinal application of carbonic acid as a local anaesthetic.2 We may consider as mild cases of poisoning by carbonic acid those attacks which often occur to those who have been long in rooms which are overcrowded and badly ventilated. These con- sist of headache, noises in the ears, with occasionally giddiness, nausea, and syncope. As a rule, these symptoms generally van- 1 Consult, for details of these, Hasselt and Husemann, loc. cit. * See Husemann, Eulenberg (loc. cit.), for details. BISULPHIDE OF CARBON. 477 ish, without any particular after-consequences, on removal from the atmosphere which induced them. If concentrated mixtures of carbonic acid be inhaled, violent symptoms of the character of dyspnoea occur. Those poisoned fall senseless to the ground, and generally succumb rapidly with symptoms of suffocation. It seems unnecessary to enter more into detail as to symptoms, because these are absolutely identical with those met with in asphyxia and suffocation. The treatment of cases of carbonic acid poisoning is also identical with that proper in asphyxia. CHAPTER VIII. POISONING BY BISULPHIDE OF CARBON. The bisulphide of carbon (CS,) owes its practical importance in toxicology entirely to its technical uses in the manufacture of India-rubber and of articles made from this. On account of its low boiling point (47° to 48° C.=116.6° to 118.4° F.) and consequent great volatility, as well as on account of its action upon animals, this poison, considered from a theoretical point of view, presents many points of analogy with the volatile anaesthetics. It is a liquid at ordinary temperatures, and its evaporation develops a good deal of cold, with the formation of characteristic strong- smelling vapor, which is specifically heavier than atmospheric air, and if fired burns with a blue flame (generating sulphurous acid). This oily, highly refractive, and generally pale-yellow fluid has a specific gravity of 1.27, and is not miscible with water, but mixes readily with alcohol, ether, chloroform, etc., etc. Bisulphide of carbon most easily finds its Avay into the ani- mal economy by the lungs, through whose capillaries the vapor of this substance, mingling easily with the air inspired, is absorbed in considerable quantity into the general mass of the blood. In what way, or if at all, it is absorbed by other organs is not yet known. Like ether and chloroform, the bisulphide of carbon, on account of its rapid evaporation and the loss of tem- perature thus induced, acts locally as a powerful irritant. Its prolonged action on the skin is that of a local anaesthetic. 478 BOEHM.—POISONS. As regards its true action on the system, and the way and manner of its elimination, there are as yet no trustworthy exper- iments or observations. It is, however, known that in those who have long breathed an atmosphere of bisulphide of carbon, the urine acquires the smell of this substance. Hermann: has found that when bisulphide of carbon is mixed with blood, the red corpuscles become dissolved. Our own observation shows the same result when fluid bisulphide of carbon is mixed with frog's blood. But the nuclei of the red corpuscles are left undissolved. It has not, however, as yet been determined whether this solvent power of the poison is dis- played in the same way in the blood circulating in a living ani- mal. According to Hermann's9 and Hirt's" experiments, which we ourselves have lately repeated with similar results, bisulphide of carbon acts upon frogs just like chloroform, ether, and alco- hol, by simply paralyzing them. If the animals thus affected with general paralysis are quickly removed from the poisonous atmosphere, they perfectly recover after a little while. The action of the heart, at first feeble, after a while ceases entirely. Hirt found that the heart of a frog, removed from the body and put into an atmosphere of bisulphide of carbon, was perfectly paralyzed after some twelve to fifteen minutes, though at first its pulsations were quickened considerably. The experiments also of Delpech,4 Cloez,5 and Hirt on mam- mals do not exhibit any remarkable difference between the action of bisulphide of carbon and that of other volatile anaes- thetics. Hirt has studied the changes in respiration and circula- tion. The former, after being considerably quickened at first, is brought to a stand-still after a few minutes—this pause, however, only lasts about sixteen seconds, and then gives place again to very rapid breathing, even when no more of the poison is exhib- ited. Section of the vagus nerves only causes a later and more gradual development of these phenomena. Hirt draws the con- 1 Archiv fur Anat. und Physiologic 1866. 2 Handbuch d. exp. Toxikol. » Die Krankheit d. Arbeiter. I. 2. 4 Nouvelles recherches sur l'intoxication speciale, que determine le sulfure de car- bone. Paris. 1860. 5 Gazette des hopitaux. 1866. BISULPHIDE OF CARBON. 479 elusion that the poison acts on the pulmonary vagus fibres as a stimulant, but on the centres for respiration first as a stimulant, and then as a paratyzer. As regards the circulation in mam- mals, Hirt found only a rise of blood-pressure, lasting for a few seconds, amounting to about 50-70 mm. of mercury in dogs and cats, which he considered as the effect of vaso-motor excitement. The disordered respiratory functions precluded any further trust- worthy observations on blood-pressure. So far we are warranted in concluding that the action of bisulphide of carbon does not essentially differ from that of other anaesthetics. But the present state of our knowledge sheds no light on the obscurity which veils the origin of those symptoms which are observed in practice as the result of chronic poisoning by bisulphide of carbon. Delpech has himself, with some prob- ability, compared them to alcoholism, and, indeed, the study of his cases and communications compels us to dra\v the conclu- sion, that the long-continued action of this poison brings about in the central nervous system degenerative changes which are simi- lar to those induced by chronic alcoholism. Cases of acute poisoning by bisulphide of carbon are rare, and must be attributed to similar causes with the more chronic forms. There have been accidents in the factories and Avork- rooms, of which we shall presently speak, through the breaking of large jars of the liquid, etc. Chronic poisoning by bisulphide of carbon generally attacks people, as has been said, employed in the manufacture of India-rubber—more particularly the red variety, used for the little toy balloons filled with hydrogen, for condoms, etc., etc. To prepare it, the caoutchouc is steeped in a mixture of bisulphide of carbon and sulphuric chloride (mostly in the proportion of 99 to 1), so that the workpeople, besides breathing in the poisonous gas, are also frequently bringing their hands in contact with the fluid. We owe the first accurate account of these circumstances to Delpech, who made careful investigations on the subject in Paris and its vicinity. Consider- ing the great extent to which India-rubber is manufactured, we cannot help, even at the outset, expressing surprise that very few other countries or places have furnished us with accounts similar to those of Delpech. Hirt expressly says that in a large 480 BOEHM.—POISONS. factory in Hamburgh which he visited, only about two in a thou- sand of the workpeople suffered from any symptoms of poison- ing. But careful reading and consideration of Delpech's report give us satisfactory reasons for this. All the French cases occurred in small establishments, in close, badly-ventilated local- ities, whilst in the larger factories great care was taken to get good ventilation. In the Paris establishments there was often such a quantity of the bisulphide of carbon vapor, that the approximation of a light caused blue flames and a slight explo- sion. It is also noteworthy, that, owing to its specific weight, the poisonous vapor formed a dense layer on the floors of the workrooms. The suspicion that the vapors of bisulphide of carbon were only partly to blame, and that the nasty smelling chloride of sulphur by its fumes might have a share in the mischief, Delpech, on the ground of experiments, sets quite on one side. Chloride of sulphur has a very high boiling point (138° C. = 280° F.), and the scanty fumes given off at ordinary temperatures, though intensely nasty smelling, do not injuriously affect either men or animals. On the ground of many careful experiments with negative results, Delpech combats the notion that it was possible that the vapors of both substances might combine into a compound with a specific action. We must, therefore, conclude that bisul- phide of carbon is the sole cause of the symptoms of poisoning in question. Age, sex, individuality, and constitution, all very consider- ably modify the susceptibility of those exposed to the poisonous action of this substance. In Paris it is thought that the habitu- ally intemperate are particularly exposed to danger from bisul- phide of carbon. Besides Delpech's twenty-four cases of chronic poisoning (of which three were also acute), there have lately been isolated cases published by Fries and Bernhardt. The symptoms of acute poisoning in human beings are not very accurately described. In the cases given by Delpech there was temporary, but complete loss of consciousness. The accounts given of chronic poisoning furnish a very char- acteristic picture, and so far as Delpech's cases go, the type is BISULPHIDE OF CARBON. 481 a constant one. The workpeople may live for weeks or even months in the poisonous atmosphere, before the severe symptoms occur, but, as a rule, they experience some inconvenience the first time they remain long in the bad air—the attacks repeat them- selves daily, and gradually get worse and worse. The chief thing is an intense, oppressive headache, spreading from the root of the nose towards both temples, with a feeling of giddiness and of intoxication (ivresse), of which the workpeople complain, when they go home in the evening. In several cases it was noticed that a more or less marked stage of excitement now developed itself. These people became remarkably lively, chatty, and excitable, and their sexual passions became greatly excited; sometimes their appetite for food also became insatiable. Ac- cording to Delpech, however, this stage of excitement is not only sometimes absent, but almost always intermingled with many symptoms of depression. All the patients, without ex- ception, complained very quickly of an evident loss of muscular strength. In later stages, many were troubled AArith remark- able loss of memory. They fell into a deep apathy, could not think, strove in vain for the words they wanted, and spoke Avith a stammering and almost paralyzed tongue. Their mental condition was strikingly obtuse, the energy of the will greatly depressed. With this were associated many anomalous symp- toms in the sensorial and motor domains of the nervous system. The faculty of vision vanished, beginning with a slight obscura- tion of the field of sight, and going on to complete inability to recognize small objects. Hearing also Avas greatly impaired, and a great many complained also of a persistent and troublesome ringing in the ears. Taste and smell were generally intact, but it was very common, particularly in the early stages, to hear the complaint that all they ate appeared to have the taste or smell of the bisulphide of carbon. The loss of muscular power was generally most noticeable in the lower extremities, and in the severer cases there Avas a considerable amount of paresis, so that the patients could only Avalk with the help of a pair of crutches, or two sticks. All movements Avere accompanied with a feeling of great fatigue. As regards sensation, there were severe lanci- nating pains in various groups of muscles, increased by pressure, VOL. XVII.—31 482 BOEHM.—POISONS. —formication,—anaesthesia of the soles of the feet, and almost constant complaints of a feeling of icy coldness in the whole of the lower half of the body; and Delpech considers that the latter symptom very probably depends on the direct action of the poi- sonous gas on the loAver parts of the body, which were constantly exposed to the thick atmosphere of the bisulphide of carbon vapors on the floor. Cramps and fibrillary contractions of various muscles and muscular groups were very seldom absent. Severe cramps in the calves very commonly harassed the patients during the night, and Delpech observed general epileptiform convulsions in several cases. The stiffness, numbness, and anaesthesia of the fingers and hands are clearly to be regarded as the local action of the poisonous fluid to which the hands were exposed. In the domain of what are called the vegetative functions the anomalies are less uniform. Apart from the rarer cases in which the appetite is enormous, digestion is almost always more or less impaired. A good many of the workpeople suffer from vomit- ing, others from severe and very often repeated attacks of colic. In the early stages of poisoning, diarrhoea and constipation alternate with one another; in the later stages, the latter pre- dominates, and is generally associated with troublesome flatu- lence. The intestinal gases are very strongly impregnated with the unpleasant smell of the bisulphide of carbon. The urine also, which is generally in normal quantity, though passed with a painful sensation of scalding, exhibits the same smell, but con- tains neither albumen nor sugar. The organs of circulation and respiration exhibit no special disorders in their action. The sexual passion, which is increased at first, rapidly de- clines at a later stage, and finally there is complete moral and physical impotence, with decrease of the size of the testicles. In women who work long in the India-rubber factories, men- struation always takes place prematurely, and is more profuse than it should be. They never have a child, and their sexual appetite becomes entirely lost. Youths who are exposed during pubescence to the influence of the poisonous gas, never develop properly. As regards the BISULPHIDE OF CARBON. 483 general condition of those poisoned, it has been noticed that a good many suffer from a febrile movement at night. Sleep is disturbed with bad dreams, generally associated with nightmare (Alpdriicken), and sometimes prevented by pains and cramps in the muscles. When the poisoning is protracted, the patients lose a good deal of flesh, but no special atrophy of muscles has been met with. Notwithstanding the severity of many of these symptoms, and the great general weakness associated .with them, an imme- diate fatal termination is very seldom a consequence. It is very remarkable, that when the patients, after a longer or shorter respite from their injurious toil, have gained some benefit in hospital, they almost always return to their work, the injurious effects of which most certainly destroy both their health and their success in life. This return to the work explains the fact that many of these cases of well-marked chronic poisoning are protracted through several years—and as the organism does not seem to get much accustomed to these noxious fumes, the symp- toms last, with more or less intensity, till the patient finally resolves to abjure forever this deleterious employment. Delpech, hoAvever, remarks that a complete restoration to health and strength, after these symptoms, is quite a rare thing. As a rule, the patients, all their life long, show marked traces of their past sufferings. They exhibit constant depression and a melancholy mood, sometimes complete apathy (Indifferentismus), and the intellectual faculties, like the power of the will and of voluntary movements, continue to be impaired and diminished. In some cases the chronic poisoning ends in some definite psy- chosis—and a good many in all probability die without our having any very definite idea of the precise mode of death. The treatment of these sad cases naturally resolves itself in great part into the fulfilment of the causal indication. Indeed, in the worst cases, one generally sees a considerable improve- ment as soon as ever the patient can be removed from the injuri- ous atmosphere. The use of tonics, and of means to restore the strength and to combat the almost universally present disorders of digestion, appears to be indicated by the dictates of common 484 BOEHM. —POISONS. sense. In this way, if the cases are not too chronic, the nervous disorders, the paresis, pains, and disorders of sensation will almost perfectly vanish without special treatment, although some general weakness and deficiency will probably remain. Delpech believes that he attained more than usual success by the administration of small doses of phosphorus (daily from one sixty-fifth to one-thirteenth of a grain) in pills—the use of which he believes to have removed actual impotence and paresis, etc. He guards himself, however, from rashness in concluding that this was definitely due to the phosphorus, but thinks the results justify a further trial of the remedy. The use of phos- phorus is generally followed at first by severe diarrhoea, but after two or three doses this becomes less severe and does not return. Fries has pointed out that partial or complete paresis of voluntary muscles may be benefited by the use of the constant current. CHAPTER IX. POISONING BY SULPHURETTED HYDROGEN (lIYDROTHION^EMIA). Sulphuretted hydrogen (hydrogenium sulfuratum, Wasser- stoffsulfid, hydrothion, H2S) is at ordinary temperatures a color- less gas, with an intense smell of rotten eggs, and it is absorbed by water with great facility, communicating to the solution the characteristic smell of the gas, a well-marked acid reaction, and an unpleasant taste (solution of hydrogen sulphide of chemists ; natural sulphur waters). Both the gas and its solution concern toxicologists, inasmuch as the poison can be absorbed by animal bodies under both forms. The gas diffuses itself very readily into the blood through the lungs, and by the mucous membrane of the digestive tract, both in Avarm- and cold-blooded animals, including human beings, and may also pass into the circulation through the skin without any wound of this covering. This absorption by the skin is proved as regards frogs by the experiments of Kaufmann and Rosen- SULPHURETTED HYDROGEN. 485 thai;' and as regards mammals, by Amelung and Falck.2 The subjects of experiments exhibited manifest symptoms of poi- soning when only the outer integuments were exposed either to the gas or to its solution. Many experiments of Nysten,* Orfila,4 Amelung and Falck (loc. cit.), Eulenberg,5 Claude Bernard," Demarquay,7 Kaufmann and Rosenthal (loc. cit.), and others, have also taught us that the gas may be injected in pretty considerable quantities immedi- ately into the veins or arteries of warm-blooded animals without giving rise to gaseous embola or other mechanical disturbances of the circulation. It appears to be absorbed by the blood immediately, and its deleterious action suddenly manifests itself. This takes place also, though less rapidly, when sulphuretted hydrogen gas or its watery solution is injected into the subcuta- neous connective tissue or into the serous cavities of animals. Although the poison may be thus absorbed into the blood through various channels, its elimination from the blood occurs principally through the lungs, for the air expired from the lungs of men and animals poisoned with this gas blackens paper previ- ously prepared with solution of plumbic acetate and moistened. In several cases of hydrothionaemia in human beings sulphu- retted hydrogen has also been detected in the urine. This was the case in three instances (one detailed by Betz8 and two by Emming- haus9) of so-called self-infection by sulphide of hydrogen (spontaneous develop- ment of the gas in the body (see farther on, p. 491), whilst Senator in a similar case fouud the urine free from this poison.10 1 Archiv f. Anat. u. Physiol. 1865. p. 659-675. 2 Deutsche Klinik. Jahrgang 1864, Nos. 89-41. 1865, Nos. 17-33. 3 Recherches de Physiologie et de Chimie pathologiques. Paris. 1811. Article VII. p. 114-130. 4 Toxikologie, ubersetzt v. Hermbstaedt. Berlin. 1818. p. 117. ' Die Lehre von den schadlichen und giftigen Gasen, etc. Braunschweig. 1865. 6 Innocuite de l'hydrogene sulfure, etc.—Gazette des hopitaux. 1857. No. 139. '• Note sur l'hydrogene sulfure, etc. Comptes rendus. Tom. 60. 1865. pp. 724-727. 8 Ueber Hydrothion-Ammoniamie. Memorabilien. 1864. p. 146. 9 Two Cases of Perforations in the Digestive Canal, with Sulphuretted Hydrogen in the Urine. Berlin, klin. Wochens. 1872. Nos. 40 and 41. 10 Ueber einen Fall von Hydrothionamie und iiber Selbstinfection durch abnorme Verdauungsvorgange. 486 BOEHM. —POISONS. In order to understand the working of this poison, it is natu- rally of the first importance that we should try to discover its action on the blood itself. Before any answer to this question was sought by way of experiment, all sorts of hypotheses were invented. For a long time it was held that the iron in the blood was precipitated as sulphide of iron. This opinion, entertained formerly by Liebig, was based on the dark color of the blood in cases of poisoning by hydrogen sulphide. Robbed of its iron, the blood could no longer be oxygenated, and thus death occurred through suffocation. Meanwhile, no one ever obtained the sulphide of iron from blood in cases of poisoning by sul- phuretted hydrogen. We owe more exact investigations into the changes produced in the blood by sulphuretted hydrogen to Hoppe-Seyler,1 Kaufmann and Rosenthal (loc. cit.), Diakonow,' and Preyer.3 The alteration in the blood of frogs when they have been long exposed to the influence of sulphuretted hydro- gen is very remarkable. The whole mass of blood in these ani- mals assumes a smutty, vivid green color, and nearly all the blood-corpuscles are destroyed. In warm-blooded animals the decomposition of the blood can never advance so far, because their more delicate nervous centres are roused into activity by far less considerable alterations in the blood. We therefore find that the blood of men or animals thus poisoned only assumes a darker tint than normal, and already in life the difference in color between arterial and venous blood has almost disappeared. But the characteristic absorption bands of oxyhaemoglobin can still invariably be recognized by the spec- troscope. But when blood withdrawn from the body of men or animals is mixed with a large quantity of this gas, the complete disintegration occurs just as in frogs, and a similar smutty green color is produced, with simultaneous separation of sulphur and of albuminous compounds. This decomposition is exhibited in a striking manner only by oxygenated blood or solutions of haemoglobin, so that it is most 1 Zeitschrift fur praktische Chemie von Huebner. 1865. p. 514.—Medicinisch-che- mische Untersuchungen. I. 1866. p. 151. 2 Hoppe-Seyler, Medicinisch-chemische Untersuchungen. II. 1867. p. 251. 3 Die Blutkrystalle. Jena. 1871. p. 158. SULPHURETTED HYDROGEN. 4S7 probable that it is due to an alteration of oxyhaemoglobin. Both Hoppe-Seyler and Preyer admit that a new chemical compound of blood-pigment and sulphur is found in this decomposition, to which Preyer gives the name "haemathion." Diakonow has also (loc. cit.) discovered some very interesting relations between the sulphide of hydrogen and the inorganic salts of the blood. The carbonated alkalies and alkaline phosphates may become con- verted into sulphides of the alkalies when sulphuretted hydro- gen is mixed with their watery solutions (and they are in solu- tion in the blood). But if atmospheric air or oxygen also be present, they have a great inclination or tendency to be con- verted into compounds of sulphurous or even sulphuric acid. Now, if a similar reaction goes on in the blood, it is clear that the oxygen of the oxyhaemoglobin would thus be diverted from its proper purposes, and appropriated by these salts. But since, as we shall see, the symptoms of poisoning by sul- phuretted hydrogen are exactly identical with those of suffoca- tion, the facts above mentioned are valuable as furnishing us with some aid toward explaining the symptoms met with in such cases. However, the present state of our scientific knowledge leaves us still in doubt whether the deficiency of oxygen which results in suffocation is brought about by the destruction of oxyhaemo- globin, and the formation of haemathion, or by the action of the poison on the salts contained in the serum of the blood; or whether, very likely, the sulphuretted hydrogen, in and by itself, irrespective of any chemical changes in the blood, has a directly deleterious influence on the mechanism of respiration. It has already been shown that the blood of men and animals thus poisoned always shows a pretty fair proportion of oxygen. It is, therefore, not very probable that, in the living body, there can be anything like that complete destruction of the blood- coloring which occurs in oxygenated blood exposed to sulphu- retted hydrogen outside the body, or that this can be the true cause of the symptoms of poisoning we observe in the living. Diakonow's discovery of the change of the salts of the blood- plasma into alkaline sulphides, and their subsequent oxidation into sulphites and sulphates at the expense of the oxygen of the 488 BOEHM.—POISONS. haemoglobin, might with more probability be regarded as the cause of the dyspnoea characteristic of this kind of poisoning, only that at present the question remains undecided, whether the sulphide of hydrogen be not a specific poison affecting res- piration. The opinion entertained by Claude Bernard (loc. cit.), and adopted by Hoppe-Seyler, that hydrogen sulphide is not injuri- ous when introduced into the veins, but kills rapidly when intro- duced into the arteries of a living animal, has not been confirmed. Nor have any satisfactory proofs been afforded of the opinion formerly held by Hoppe-Seyler (loc. cit,), that the sulphur, which Avas set free or precipitated in the blood in cases of poisoning by sulphuretted hydrogen, brought about death by forming capillary embolisms in the lungs. The experiments of Kaufmann and Rosenthal as to the inju- rious effects of this poison on the cardiac movements are more satisfactory. The symptoms observed consist in a primary re- tardation of the pulse, and diminished blood-pressure dependent on central irritation of the vagus nerve, and the consequent gradual but steady decrease of the activity of the heart, ending in diastolic stoppage of this organ; and they agree closely enough with the disorders of the circulation observed after poisoning with carbonic oxide or simple suffocation. All the remaining symptoms, too—particularly the convulsions preceding death, and the disordered functions of the brain—find their simplest explanation when regarded as symptoms of suffocation. Authors generally' agree in considering sulphuretted hydro- gen as one of the most powerful and deadly poisons. As a mat- ter of fact fatal poisonings by this gas are not uncommon, and the frequently violent and rapid course of such cases would seem to amply justify such a classification. However, it must not be forgotten that in ordinary life many men from day to day inhale considerable quantities of this gas without suffering any ill effects. 1 Christison, R., Treatise on Poisons, German translation, Weimar, 1831, p. 819, calls sulphuretted hydrogen "the most injurious gas known." See also v. Hasselt- Henkel, loc. cit. p. 376, and Husemann, loc. cit. p. 749. SULPHURETTED HYDROGEN. 489 We refer to laborers in dung-pits, cesspools, privies, chemical laboratories, etc. The Parisian vidangeurs are said to generally enjoy very good health, and during the cholera epidemic in Paris in 1832 it appears that they suffered from that disease even less than other people.1 Besides this, it is to be considered that in most of the fatal cases which have occurred of poisoning by sulphuretted hydro- gen, very enormous quantities of this gas have been required to kill, whilst there has simultaneously been an almost total depri- vation of atmospheric air. We cannot, therefore, rank sulphu- retted hydrogen in quite the same class with prussic acid and similar poisons, which kill in almost minimal doses, and we can- not call it one of the strongest poisons. The fatal cases are far from numerous, if we consider the number of occasions on which workingmen are exposed to the action of this gas. It is, Iioav- ever, a striking fact that when one dies thus it is common for several to perish together, generally from want of caution, and from imprudent attempts to rescue the first victim, fresh victims falling a sacrifice to the fate of the first. Numerous cases of this kind are recorded, as that of Casper,2 where six healthy men perished in a tan-pit, through a mixture of gases strongly impregnated with sulphuretted hydrogen. Amongst the numerous conditions and circumstances giving rise to poisoning by sulphuretted hydrogen, the following de- serve especial notice: In a few localities only, very close to large volcanoes (Solfa- tara of Puzzuoli, near Naples, and some parts of Sicily), the sul- phuretted hydrogen formed in the interior of the earth, and escaping in dense vapors from its crust, may give rise to cases of poisoning. Such cases are more commonly noted through the use of mineral waters strongly impregnated with the gas, although severe cases of poisoning from this cause also are not very common. As a rule, the sulphuretted hydrogen found now and again in the air is due to the decomposition of animal and vegetable substances. In this way, as Fr. Daniell3 has shown, 1 v. Hasselt, loc. cit. p. 380. 'l Handbuch der gerichtl. Medicin. II. p. 598. 3 Philosoph. Mag. and Journal. III. Ser. July, 1841. Consult also the article "Air" in Tardku's Dictionnaire d'hygiene publique et de salubrite. 2. Ed. Paris, 1862. 490 BOEHM.—POISONS. enormous quantities of this gas are generated on the coasts of Africa, when the large rivers debouch into the sea, by the decom- position of the sulphates of the sea-waters by the great quantity of decomposing vegetable substances which the rivers are carry- ing towards the sea. These cause numerous cases of poisoning amongst seafaring people. The putrid decomposition of animal substances is the richest source for the generation of hydrothion gas, and this is the most frequent cause of cases of poisoning, since these sources of danger are most naturally to be found in the immediate vicinity of human habitations. And, although the sulphuretted hydrogen in these cases is almost without exception mingled with other gaseous products of putrefaction, such as carbonic acid, ammonia, etc., yet experi- ence has taught us that it is almost exclusively the sulphuretted hydrogen which constitutes the poisonous and dangerous part of the mixed gases. The most important substance (Muttersub- stanz) for generating sulphuretted hydrogen in sewers and cess- pools, is human ordure. For, although urine in decomposing may give rise to the formation of this gas, by the decomposition of its sulphates, yet the mixture of gases found in putrid urine owes its chief properties to ammoniacal gas. But when faeces are present in large quantities, the remains of undigested albumi- nous bodies, such as gelatine, etc., afford a material richly capa- ble of furnishing enormous quantities of sulphuretted hydrogen. Accordingly, the quantity of this gas present in the gases given off from privies, etc., will greatly depend on the richness or poverty of the albuminous constituents of the food. The closets and cesspools used entirely by the proletariat, like those of convents, will therefore be far less dangerous to the scavengers (vidangeurs) than those of the upper classes, who take a superior diet, more rich in albuminous com- pounds.1 But many other kinds of animal substances afford materials for the generation of sulphuretted hydrogen—pits in which ani- mal excreta are collected, flayers' and knackers' yards, badly regulated churchyards, sewers, dissecting-rooms, dirty slaughter- houses, where small fragments of meat, etc., are allowed to de- 1 v. Eulenberg, loc. cit. SULPHURETTED HYDROGEN. 491 compose, cesspools, and other similar places belong to this category. In special cases it will depend entirely on the density of the accumulations of the gas as to how far and in what degree it gives rise to cases of poisoning. In this category we must also include those cases where drinking-water impregnated with sulphuretted hydrogen has led to cases of poisoning.1 In the present state of our knowledge, we can only say that it is supposed that under some circumstances the living body may be self-infected by the generation within itself of sulphu- retted hydrogen, "self-poisoning," as it has been termed. The number of recorded cases of this kind is very small, and the necessary conditions for their occurrence are as yet little knoAvn. The painstaking researches of Planer2 tend to show that in normal digestion the gases which are generated contain very little sulphuretted hydrogen, which never exceeds one per cent, of the whole quantity. In the intestines of herbivora, or of men fed exclusively on a vegetable diet, no trace of sulphuretted hydrogen is found. This originates chiefly in flesh diet, in the lower portions of the large intestine. Abnormal development of gases, and hence generation of sulphuretted hydrogen, occurs in the stomach when its free acids are neutralized. That the bile is not the original cause of the development of this gas is certain from the fact that it does not occur with a vegetable diet—a fact which also shows that we are justified in reckoning the albumen compounds as the source of this gas (H2S), and that animal albumen is of especial importance for generating sulphuretted hydrogen. The occasions which may give rise to self-poisoning by the generation of this gas in the digestive canal may originate from within, especially in certain forms of chronic gastric disorders, in which very probably the free acids of the gastric juice are sup- pressed, in consequence of abnormal processes of fermentation. Very likely this was partially so in the cases detailed b/v Betz (loc. cit.), whilst Senator (loc. cit.) places the generation of gas in the caecum. In the cases of "self-poisoning" lately observed by Emminghaus (loc. cit.) there were several perforations of the digestive canal, and these had led to putrid decomposition of the faecal matters, and to suppuration. 1 See Th. Clemens, on an epidemic of boils, originating in the use of a sulphuretted well-water. Zeitschrift f. rat. Medicin, von Henle und Pfeufer. VIII. 1849. p. 215. 2 The Gases of the Intestinal Canal, and their Relations to the Blood. Wiener Sitzgs.- Ber. Mat.-Phys. Kl. XLIV. 1860. p. 307. 492 BOEHM. —POISONS. According to Biermer,1 large quantities of sulphuretted hy- drogen may be present in the fluid exudations of pleurisy with pneumo-thorax, and may perhaps lead to self-poisoning, and this gas may also frequently be demonstrated in the sputa of tuberculous patients, and of those who suffer from broncho- blennorrhcea. The poisonous gas may thus be absorbed in self- poisoning, either from the mucous membranes of the gastro- intestinal tract, from serous membranes, or from suppurating surfaces and cavities. Many kinds of factories and works furnish a number of opportunities of poisoning by sulphuretted hydrogen; in these the workpeople find themselves in a more or less dense atmos- phere of sulphuretted hydrogen, either only very occasionally and by accident, or sometimes almost constantly. Eulenberg (loc. cit.), in his monograph on Injurious Gases, has very carefully examined this question, and from his collection we select the following: The chief trades and occupations which are exposed to sulphuretted hydrogen are: a. The catgut makers. In the process of steeping the fresh sheep's intes- tines, large quantities of offensive gas, containing much sulphuretted hydrogen, escape into the air. I. The tanners' yards. In this trade the occasional use of the so-called "gas lime" for the skins, containing, as it does, calcium sulphide, develops large quantities of sulphuretted hydrogen when acid decoc- tion of tan is added. Dangerous cases of poisoning are thus caused. The same thing may occur in the preparation of Morocco leather (Saffi- angerberei), in which the so called "rusma," a mixture of sulphide of arsenic and lime, comes into use to free the skin from hair. Here again the acid decoction of tan generates great quantities of gas. c. In the process of flax steeping, cases of poisoning by hydrogen sul- phide occur. In this the flax is steeped under water till the parts of the flax which are not useful have decomposed, and thus the genera- tion of sulphuretted hydrogen is unavoidable. d. Similar processes are employed in the manufacture of sugar and starches. In the sugar manufacture it is more particularly the so- called "revivification" (Wiederlcben), or purifying of the animal charcoal which has been once used for filtration, which gives rise to so much generation of sulphuretted hydrogen, when this is done by the so-called " moist fermentation," which leads to the putrefaction 1 Ueber Pneumothorax. Schweitz. Zeitschr. 1863. SULPHURETTED HYDROGEN. 493 of the albuminous bodies retained by the charcoal; also when much blood is used in the sugar-houses. e. The so-called " wash " (Schlempe) or residuum of the molasses which has been treated by the distillers with sulphuric acid, develops, by keeping, very large quantities of sulphuretted hydrogen gas, which may easily lead to accidental poisoning, if there be any want of caution. /. In the same way, the steeping water of the brewers, in which barley has been steeped for the purposes of malting, will generate sulphu- retted hydrogen if allowed to stand long. Still more frequent opportunities of poisoning by the sul- phide of hydrogen arise in chemical works of various kinds. First, we have the generation of the gas from sulphide of iron with sulphuric acid in the laboratory, which is often far too care- lessly undertaken and frequently gives rise to accidents. Of chemical works, the most notable are the ammonia works, in which ammonia and its salts are made from urine and from the gas-tar liquor (ammonia water) of the gas-works. But especial mention must be made of the manufacture of coal-gas by dry distillation of bituminous coals (Blatterschiefer), and of the sul- phuring of India-rubber in the India-rubber factories. It is especially incumbent on medical men, who are much concerned in factories of various kinds, to acquaint themselves with the injurious products of the various manufactures. Against the formerly prevalent opinion, that the so-called "miners' sickness," which often attacks those employed in the shafts of mines in which blasting goes on — causing sudden symptoms of syncope, etc., etc., Avas due to the development of sulphuretted hydrogen from the gunpoAvder used, very weighty objections have lately been raised. In particular, Poleck' has shown that the quantity of hydrogen sulphide actually present in the mine is too small to be quantitatively determined, and is a continually diminishing quantity. In the same way it has never been demonstrated satisfactorily that the gases, which are sometimes found in tunnels and other underground places, and which lead to accidents Avhen there is but little access of air, are really injurious from containing sulphuretted hydrogen. 1 Die chemische Natur der Minengase und ihre Beziehung zur Minenkrankheit. Ber- lin. 1867. 494 BOEHM.—POISONS. If the system be exposed to a large quantity of this poisonous gas all at once, the symptoms and course of poisoning by sul- phuretted hydrogen will not unnaturally differ very materially from the effects of smaller doses of the poison, operating repeat- edly and for a longer time. Accordingly, it is generally very material whether, and in what quantities, the access of atmo- spheric air be possible. Acute and quickly terminating cases of poisoning are almost without exception the result of direct breathing in of the poison, and it would seem, under some circumstances, that a very few Avhiffs of a thick atmosphere of sulphuretted hydrogen are sufficient to cause death to human beings. In the chronic cases, either of "self-poisoning" or of poisoning by drinking-water, smaller quantities of the poison, during a long period, find access to the blood, through mucous or serous membranes. The quantities necessary to kill, or to produce dangerous symptoms, in gaseous mixtures, have not, as may be supposed, been quantitatively determined, with any degree of accuracy, as regards human beings. Hence, we abstain from giving any fig- ures on this subject. Breathing a mixture containing a medium quantity of this gas, even for a very short time, produces a condition closely akin to common nausea : a general feeling of weakness with headache, inclination to be sick, with characteristically smelling eructations, vomiting, and sometimes colic and diarrhoea. With the exception of the smell of the eructations or vomit—and this is not invariably present—the symptoms present nothing charac- teristic or pathognomonic, and in the course of a few hours health is generally perfectly restored. On the other hand, the most severe symptoms occur when large quantities of the poison- ous gas are breathed in all at once. It is by no means rare for men thus poisoned to fall to the ground with a cry as if struck by lightning. This worst form of poisoning has been observed, for the most part, where persons have been engaged in sewers or drains which have not been opened for a long time. In less severe cases, the person attacked feels a quickly increasing sense of Aveakness, which goes on to syncope, and after a few minutes he becomes unconscious. The breathing, quickened at SULPHURETTED HYDROGEN. 495 first, becomes gradually slower and more difficult, and acquires the character of true dyspnoea. The pulse becomes weak and irregular, the skin cool and covered with cold sweat, and the countenance livid, the mucous membranes cyanotic, and the abdomen distended by extreme meteorism. With these are asso- ciated muscular cramps, at first localized, but gradually becom- ing general; all reflex action is lost, and, last of all, death occurs Avith violent convulsions. The descriptions of different authors differ from one another only in very slight and unimportant particulars. Thus some describe furious delirium, whilst others mention trismus and tetanus as complications. And although the clinical picture of acute poisoning by sulphuretted hydrogen has not yet been drawn very accurately—for instance, we have no precise observa- tions as to pulse, temperature, excreta, etc.—yet we are able, from the materials before us, to refer all the symptoms observed, with great probability, to the disorders of respiration—Avhether the altered properties of the blood, or a direct action on the nerves brings about this disorder, seems immaterial. If re- covery takes place, as with timely and appropriate treatment it often will, the after consequences and sequelae are, as a rule, very slight. The encephalitis which some authors have noted as a sequela can scarcely be considered to arise in direct con- sequence of the poisoning by sulphuretted hydrogen. And the terminal convulsions, which have been attributed to direct irrita- tion of the spinal cord, Ave, on the contrary, unhesitatingly con- sider as spasmodic movements due to suffocation. Unmistakable cases of chronic poisoning by sulphuretted hydrogen, apart from those instances of " self-poisoning " previ- ously mentioned, are very rarely recorded, and the accounts of them are not very accurate. At the beginning the symptoms usually consist in subacute gastritis, with frequent hiccup and vomiting, constipation, colic, jaundice, etc., and a number of general nervous symptoms, such as lassitude, headache, vertigo, etc. V. Hasselt (loc. cit.) thinks that the tout ensemble of the symptoms of poisoning in these cases is very similar to, and may be mistaken for, subacute forms of typhus or rather typhoid fever. 496 BOEHM.—POISONS. Th. Clemens (loc. cit.) saw a number of workpeople in a chemical factory fall ill, one after the other, in the space of a few days, with general weakness of the extremities, want of appetite, oppression at the stomach, and vomiting—from, as it afterwards turned out, the use of well-water impregnated with sulphuretted hydrogen (Hydrothionsaure). The pulse was remarkably slow and easily com- pressible. All the secretions were sluggish, and the dry, cool skin had lost its usual turgescence or tonicity. In from four to ten days after the first stomach symptoms, the skin of the face, head, and hands, less often of the chest and extremities, was attacked with painless swellings, not actively inflamed, but soon developing into pustules and boils, with a great tendency to scabbing. Each boil was about the size of a hazel-nut. As soon as the skin became affected, the general symptoms ameliorated, only a peculiar blunting of the sense of taste remaining for a long while. Sulphuretted hydrogen was clearly proved to be the cause, and the fulfil- ment of the causal indication (leaving off the use of the water) led to rapid recovery in some cases where other means had long been tried in vain. In the cases frequently mentioned before, of "self-poisoning,"' the beginning of the poisonous action was either indicated by a change of the previous symptoms (Emminghaus), by the general health suddenly declining, the occurrence of a bluish coloration of the face, the finding of the poison in the excreta, and, as the malady gained power, by death ensuing, or the symptoms men- tioned above as indicating chronic poisoning were present in a more or less marked degree (Betz, Senator). The post-mortem appearances in men dying from poisoning by sulphuretted hydrogen agree very closely with those found in suffocation. Indeed, except the not invariably present smell of hydrogen sulphide, which may also occur as a putrefactive phenomenon in other corpses, there is a total absence of any characteristic or pathognomonic symptom of hydrothion gas poi- soning. Some authors, and indeed Casper (loc. cit.) in particu- lar, have insisted on the inky blackness of the blood, and on the simultaneous discovery by the microscope of broken-up red blood-discs. But very little importance can be attributed to the often mentioned venous hyperaemia of the organs of the central nervous system, or to the various colors of the mucous membrane of the intestinal tract, which have been specially mentioned by Fabius and Devergie.' It is almost self-evident that the very first point in the treat- 1 See Husemann, loc. cit. SULPHURETTED HYDROGEN. 497 ment of poisoning by sulphuretted hydrogen must be to get the patient out of the injurious atmosphere. But, as has been said above, the fulfllment of this indication very often causes fresh victims ; and, therefore, very great caution is necessary in their deliverance. A number of prophylactic regulations to guard against the poisonous gas have been proposed by one and another. Most of these belong rather to the domain of legal san- itation. But if one be desirous to remove an unfortunate fellow out of a very dense atmosphere of sulphuretted hydrogen (as, for example, from a sewer, or the pit of a closet), since any previous disinfection of the place is generally impossible, use may be made of a sponge dipped in a solution of chlorinated lime, and bound in front of the mouth—although Ave cannot guarantee the abso- lute safety of even this plan. In very limited spaces, the hy- drogen sulphide may be set on fire. But the safest and most serviceable method in all cases would be for those who enter the poisonous atmosphere to be provided with a mask for the face, like that used by divers, with a tube attached, communicating with the outer air. Such masks must of course be considered as part of the indispensable outfit for scavengers.l Most toxicolo- gists (Hasselt, Husemann, and others) recommend beginning fur- ther treatment with an emetic, to get rid of anything swallowed. Tartar emetic must not be used, as this would be decomposed by the poisonous gas. And Clemens states that he found antimony useless in these cases. Instead, however, of using ipecacuanha, as Hasselt recommends, it would perhaps, in the present day, be better to use apomorphia, subcutaneously injected. Artificial respiration, as soon as ever any failure of natural breathing occurs, seems far more desirable than emetics. Many authors recommend the inhalation of chlorinated soda, chlorine water, solution of chlorinated lime, and, indeed, of chlorine itself, in order to render harmless any hydrogen sulphide present in the blood. But, as Husemann justly says, such measures are not quite free from danger, for chlorine itself must be considered as 1 [Where no apparatus is at hand, holding the breath and attaching the body to a cord held by those in safety may sometimes succeed. And a bit of flexible tubing might possibly be obtained at short notice, in large towns, and inserted in the nostrils or mouth, so as to keep up connection with pure air.—Trans.] VOL. XVII—32 498 BOEHM.—POISONS. a poisonous gas. Besides, the gas appears to be eliminated in a natural (physiological) Avay with quite sufficient rapidity, pro- vided only that the respiratory process can be kept efficiently going. CHAPTER X. POISONING BY PRUSSIC ACID AND ALLIED SUBSTANCES (VENENA CYANICA). The practically important poisons of this group all act in pro- portion to the prussic (hydrocyanic) acid they contain or repre- sent; they are partly products of the vegetable kingdom, and partly artificial chemical products. Pure cyanogen gas itself possesses intensely poisonous properties, which seem analogous to those of prussic acid. We need not, however, devote any space to the consideration of this gas, as it is not of any impor- tance or significance in practical toxicology. In the vegetable kingdom, prussic acid is generated through the action of an albuminous ferment, emulsine (Synaptase), on the nitrogenous glucoside, amygdalin. The action of these two substances on one another generates prussic acid, sugar, and oil of bitter almonds. A poisonous action has very often, but erro- neously, been attributed to the latter essential oil, but recent investigations have shoAvn that Avhen chemically pure, and per- fectly free from the prussic acid which is so firmly combined with it in general, it possesses no action beside that common to other essential (ethereal) oils. The oil of bitter almonds met with in commerce is, however, as a rule, strongly impregnated Avith prussic acid, and therefore intensely poisonous. The reaction o£ emulsine on amygdalin, so deeply interesting from a chemical as well as from a toxicological point of view, only takes place in the presence of water, and does not happen if the emulsion has been heated to the temperature of boiling water (100° C). The fer- ments found in the bodies of animals, and particularly the gas- tric juice, appear to prevent this action of emulsine. Emulsine and amygdalin themselves do not appear to possess any poison- PRUSSIC ACID AND ALLIED SUBSTANCES. 499 ous properties. That other substances originating in the bodies of animals can decompose amygdalin and form prussic acid appears probable, as regards rabbits, from the experiments of Koelliker and Mueller.1 The substances generating prussic acid are found more especially in bitter almonds, the fruits of amyg- elalus communis, var. amara, and in the cherry-laurel (prunits lauro-cerasus) ; also in the stones and kernels of peaches and plums, and several other members of the amygdalaceae and pomaceae.8 Amongst the chemicals containing prussic acid, the only generally important ones are prussic acid itself (hydrocyanic acid, HCy), and its alkaline salt, the potassium cyanide, (KCy). Some few cases are recorded of poisoning by ammonium, zinc, and mercury cyanides. As prussic acid is to be regarded as the essentially poisonous principle in all these, Ave propose to discuss the action of this acid, for all that is said about this may, with very slight individual modifications, be extended to all the other combinations of cyanogen. The most important toxicological character common to all the cyanogen compounds is the characteristic smell of bitter almonds which they either exhibit, from the very first, or develop after solution or decomposition in the juices of the animal body. As regards prussic acid, it is to be noted that it is rare to meet with cases of poisoning from the anhydrous or concentrated acid. Most of the poisoning cases occur with various strengths of dilute acid. The strength of the various officinal preparations of prussic acid varies in different countries from 1 to 15 per cent. of anhydrous acid.a Prussic acid is very volatile, and is soluble in water and alco- 1 Verhandlung der physikal.-med. Gesellschaft zu Wiirzburg. 1856. 2 See Husemann, Pflanzenstoffe, p. 684, etc. 3 According to Husemann (Toxikologie, p. 711), the officinal hydrocyanic acids con- tain as follows: in the Prussian, Bavarian, Austrian, American (U. S.), London, Dutch, Hanoverian, and most other pharmacopoeias, 2 per cent, real acid. The Edinburgh pharmacopoeia directs 3.2 per cent; the Dublin, 1.6 to 2.82 per cent; the Wurtem- berg, 3 per cent., and the French, 15 per cent. A strictly accurate and certain deter- mination of the strength in real acid of any solution is, however, as Husemann insists, a problem which offers considerable difficulties in its solution. 500 BOEHM.—POISONS. hol under almost all conditions. Potassium cyanide is a very hygroscopic crystalline compound, easily soluble in water, and alkaline in its reaction. For the other physical and chemical properties of the venena cyanica we refer the reader to hand- books of chemistry and pharmacy. The absorption of hydrocyanic acid into the animal body takes place very easily, and in several different ways, on account of the volatility of this compound and its easy solubility in watery fluids. The rapid action of its vapor, when inhaled, is well known ; and its absorption into the blood is not much less rapid when applied to the mucous membrane of the digestive tract, to the subcutaneous connective tissue, or to raw surfaces, such as wounds. Its more rapid action, when ingested by the organs of respiration, is easily explicable when we consider that the large absorbing surface of the lungs enables a great quantity of this easily diffusible poison to reach the mass of the blood. Preyer's' opinion, that in this way of application there is an immediate stimulation or irritation of the peripheral branches of the vagus in the lungs, appears to us not justified by facts. Apart from the fact that the poison acts still more rapidly Avhen injected into a vein, Preyer's view is not supported by the circumstance that even Avhen the vagus is divided the ingestion of prussic acid gives rise to most violent symptoms of poisoning. To this we must add that the most recent researches—as will presently be further explained—leave it doubtful if the peripheral branches of the vagus play any particular part in poisoning by prussic acid." We do not consider that it has been proved that prussic acid can be absorbed by the skin, in the absence of any injury to that tissue, in quantities sufficient to poison. In regard to this we are at one with Preyer, who doubts Kuehne's assertion that gaseous hydrocyanic acid can penetrate the uninjured skin. For, apart from the probability of slight abrasions of the epithelial Jayer of the skin being overlooked, it is quite possible, in these cases, for the vapor of the acid applied to the skin to come in contact with the air-passages, and thus to get absorbed by the lungs. We do 1 Die Blausiiure, etc. Bonn 1868-1870 2 See Archiv f. exp. Pathol, und Pharmakologie. Bd. II. PRUSSIC ACID AND ALLIED SUBSTANCES. oOl not absolutely deny the possibility of absorption by the external integuments; for this poison is clearly not an indifferent agent as regards the skin, as is clearly proved by its local effects (in lotions, etc.), which are testified to by many observers. For if the feelings of insects crawling (Ameisenkriechen) and numbness, which follow the soaking the finger-tips in solutions of prussic acid, are considered only as affections of the local terminations of the sensory nerves, yet still, in any case, the poison must have penetrated the epidermis. And once admit this, there is then no special obstacle to the further absorption of the poison in this way. But the passage of large quantities of the poison into the blood in this way seems to be hindered by the diffusion of the bulk of the poison into the surrounding air. But a few experiments, made with the necessary precautions, ought to be capable of easily settling this point. Preyer, and also Coullon and Callies,'' at an earlier date, did not observe any symptoms of poisoning follow the application of dilute prussic acid to the shaved skin in dogs and rabbits. But absorption through every possible mucous membrane, through serous membranes, and through the subcutaneous connective tissue, has been established beyond doubt by numerous experiments and observations, both old and new. But can poisoning occur without the blood being implicated? Can this poison act without having passed into the blood ? The results of experiments in which this poison has been applied to nerve-trunks laid bare, and to the surface of the nervous centres, would lead us to answer this question in the negative. The elim- ination of prussic acid from the animal2 organism has not yet been studied Avith much accuracy, and the opinion that it takes place chiefly by the lungs and skin is based on the rather uncer- tain detection of the smell of prussic acid in the expired air, and in the perspiration of those poisoned. As regards the behavior of the absorbed prussic acid in the organism, almost the only certain fact appears to be that, as a 1 See Preyer, loc. cit. pp. 41, 43. 2 Consult Preyer for experiments by Emmert, Wedemeyer, Schubarth, Gottwald, Kuerschner, and Krimer. 502 BOEHM.—POISONS. rule, it is always possible to demonstrate a certain amount of undecomposed or free hydrocyanic acid in the blood. The dis- covery made by Preyer and Hoppe-Seyler,1 that the blood-pig- ment forms a crystalline compound with prussic acid, appears to us to help our explanation of the symptoms in cases of poison- ing by prussic acid, very much in the same way as the analogous discovery of carbonic oxide haemoglobin does, in poisoning by carbonic oxide. But in this case the combination of the poison with the haemoglobin has been demonstrated in the blood of liv- ing animals thus poisoned, whilst, as regards prussic acid poi- soning, this is not yet the case. Schoenbein' s experiments 2 have shown that hydrocyanic acid changes the vital properties of the red blood-discs, and robs them of their power of liberating oxy- gen from the peroxide of hydrogen. The external phenomena due to the action of prussic acid are especially centred, in all Avarm-blooded animals, in disturbances of the respiratory movements; these are either more or less quickly abolished, or are excessively retarded. As a rule, the typical poisoning case commences with ten or twelve unusually hurried respirations, which are immediately succeeded by an attack of tetanic convulsions, during which the diaphragm remains contracted and immovable. Should the animal not die, as it generally does in this attack, then all the muscles become relaxed, and deep respirations succeed with very short mspira- tions, strikingly long expirations, and unusually long intervals between the individual breaths. If the animal recovers, these respiratory pauses gradually give way to more natural breath- ing ; but if it does not recover, death ends the scene in less than an hour, without any fresh convulsive attack. After the first convulsive seizure, all reflex irritability and sensation are totally lost; but both return should the breathing again become normal. A number of observations have been made in order to try to explain the disordered respiration. Thus, Gaehtgens3 has dis- 1 Med. chem. Untersuchungen und Virchow's Archiv. Bd. 38. 1867. See also Preyer, Blutkrystalle and loc. cit. 2 Zeitschrift fiir Biologie. Bd. III. p. 140. 3 Hoppe-Seyler, Med.-chem. Untersuchungen. p. 346. PRUSSIC ACID AND ALLIED SUBSTANCES. 503 covered that the chemistry of respiration undergoes a change. The quantity of carbonic acid in the expired air is remarkably lessened during the poisoning, as compared with healthy ani- mals, whilst the quantity of oxygen in it exceeds that of normal expired air—a result diametrically opposite to the rule of ordi- nary suffocation, and one not easily explicable by the mere admission of a simple disturbance of the mechanism of respira- tion. Gaehtgens' results led him to suspect that animals poi- soned with prussic acid form less carbonic acid than usual, snd take in less oxygen than the normal amount, so that, during the acme of the poisoning, the processes of oxygenation in the sys- tem are almost suspended. The physiological experiments of Preyer on the disorders of respiration in poisoning by prussic acid do not elucidate the question much, since they have not been confirmed by other investigators. Preyer insists on the action of the poison on the peripheral pulmonary branches of the vagus, and ascribes the fatal result to the irritation of these organs. He considers that his experiments justify the view that otherwise certainly fatal doses will not kill animals in whom the vagus has been divided, and indeed that such animals no longer die suffocated, but only from the paralyzing action of the poison on the heart. In an analogous way, Preyer holds that atropine, which paralyzes the vagus, preserves an animal from being suf- focated by prussic acid. The author has lately repeated Prej^er's experiments in conjunction Avith Knie,1 but has not succeeded in obtaining the same results. On the contrary, he finds that sec- tion of the vagus nerves and atropine do not in any way mod- ify the action of prussic acid. On the other hand, he was able to show that, at the acme of prussic acid poisoning, irritation of the central vagus fibres had no effect on the breathing, and did not stimulate the relaxed diaphragm to any contraction. And his results contradict Preyer's view, that respiration in prussic acid poisoning exhibits a spasmodic character as regards the mspirations, for, except in the first convulsive seizure, he never saw inspiratory tetanus as a result of prussic acid poison- ing, but always found, in the pauses between the breathing, 1 Archiv f. exp. Path, und Pharm. II. 1874. 504 BOEHM. —POISONS. that the diaphragm was in the position of expiration, i. e., at rest. Next to the action on respiration, most attention has been devoted to the action of the heart in poisoning by prussic acid. In cold-blooded animals (frogs) this poison causes a very consid- erable decrease in the number of the apex-beats, and sometimes even at the commencement a diastolic arrest or stand-still, which subsequently yields to irregular and weak contractions. Preyer attributes very great importance to the cardiac vagus in prussic acid poisoning, and when the doses are not too large, attributes the whole of the symptoms to the changes in the innervation of the vagus—that is, to a temporary irritation or paresis of the inhibitory vagus. The absolute stoppage of the heart by very large doses is attributed to a direct paresis of the automatic nerve-centres of the heart itself (due to deficient oxygenation of the blood). The author's experiments in this direction, however, yielded results very different from those of Preyer. He could not establish in the least degree, that the inhibitory vagus is at all implicated by the action of prussic acid on the organs of circula- tion. The stoppage of the heart always followed the cessation of respiration, and never preceded it, no matter whether section of the vagi had been performed or not. It was never possible in cats to observe any stoppage of the heart by direct irritation of the A'agus in an early stage of the poisoning. Indeed, we Avere led to the conclusion, that it is by no means easy to kill the heart by doses of prussic acid. For if death by asphyxia Avere hindered by artificial respiration, even when enormous doses of the acid were given, the heart beat regularly, though rather slowly, until the animals finally recovered from the poisoning. The blood-pressure and the pulse-frequency, after being slightly increased for a few seconds by prussic acid, became considerably lessened." Experiments on cold-blooded creatures (frogs) and other ani- mals, for the most part, agree with one another, and lead to the conclusion, that for all classes of animals this is one of the most deadly poisons. We need not here give references to these in detail. It may be propounded as a general rule, that the more active the tissue-changes in any animal are, the more sensitive PRUSSIC ACID AND ALLIED SUBSTANCES. 505 will it be to the action of the poison. For example, birds suc- cumb most quickly and completely, whilst cold-blooded animals, like frogs, whose respiratory needs are slight, succumb rather slowly to the action of the poison, which in them seems almost limited to a gradual annihilation of the power of voluntary movements, whilst fishes are still more slowly affected by prussic acid.1 It will be seen, however, that numerous as are the experi- ments and observations on the poisonous action of prussic acid, and varied and many-sided as are the points of view in which we may regard them, yet when we attempt to draw any conclu- sions as to the precise manner in which this poison acts, we are met by precisely the same kind of difficulties which prevented our coming to a definite conclusion in the case of poisoning by carbonic oxide, sulphuretted hydrogen, and other poisons. This is just that interesting group of poisons which appears to us to offer for the first time, in the dark domain of toxicology, points of analogy and resemblance between purely physiological and physiologico-chemical effects. But this only makes it more dan- gerous to draw premature conclusions, or accept crude theories. But until something more is known we are justified, in the pres- ent state of our knowledge, in concluding :— That prussic acid has an extremely prejudicial action on the respiratory functions of warm-blooded animals. And that paresis of the respiratory centres appears to be the real cause of death in this mode of poisoning under all sorts of circumstances. The action of prussic acid on the heart and circulatory organs originates partly in the respiratory disturbances and partly in a directly paralyzing effect of the poison on the vaso-motor nerves; in animals free from injury the latter is never a cause of death. We consider the convulsions of prussic acid poisoning as the expression of a transient but energetic irritation of the central apparatus of the brain and spinal cord, and do not think they can be identified with the ordinary convulsions met with in sim- ple suffocation. What role the above-mentioned changes in the 1 See Preyer (loc. cit. II. p. 45 et seq.) for details on this point. 506 BOEHM.—POISONS. chemistry of the blood and of the tissues play in the state of things brought about by prussic acid poisoning is at present absolutely dark and obscure, and, until something further is dis-' covered, the opinion of a directly poisonous action of hydrocy- anic acid on the functions of the central nervous system seems to be the only possible explanation. Suicidal attempts and medi- cinal poisonings by misadventure furnish the greater number of cases of poisoning by prussic acid ; but Avith these are associated also a few cases of purely accidental poisoning, particularly in consequence of the modern technical applications of potassium cyanide (in gilding, silvering, etc.) and the use of vegetable substances containing prussic acid as articles of diet. Unfortu- nately, there is a deficiency of any very precise determination of facts in the recorded literature. Tardieu and Roussin very prop- erly remark that it is quite possible that a large number of cases of poisoning by prussic acid are never discovered, and that it AArould be very erroneous to attempt to draw any conclusions as to the frequency of these cases from the number of those re- corded. It is therefore almost a matter of astonishment that the number of known suicides by means of venena cyanica is so small. Without, therefore, attaching any undue importance to mere numbers, we record some figures taken from a collection of the more carefully recorded cases of poisoning by prussic acid from the literature of the last tAventy years. Of 35 cases 13 were medicinal poisonings, 11 Avere suicidal, 6 were economic or acci- dental poisonings in trades, etc., and 5 were designated as mur- ders. Only 2 recovered, whilst 33 ended fatally ; 30 of these were in males, and 5 in females. Of the medicinal poisonings some were due to the prescriber's mistake, and some to the fault of the compounder in mistaking the dose. In the celebrated case at the Bicetre in Paris, recorded by Orfila,1 seven men fell victims to the stupidity of an attendant, or male nurse, who gave them an overdose of a prussic acid mixture. Accidental poisonings sometimes happen in surgeries and chemists' shops ; thus the breaking of a flask filled with strong prussic acid proved fatal to an apothecary's apprentice, who succumbed to the rapidly dif- 1 Annal. d'hygiene publ. 2. ser. XXX. 1868. PRUSSIC ACID AND ALLIED SUBSTANCES. 507 fusing fumes of the poison. Similar cases occur in chemical laboratories ; thus the death of the celebrated chemist Scheele is 'known to have been caused in this way. How very little inju- rious the contact of solutions of potassium cyanide with the uninjured skin really is, the daily experience of photographers constantly shows. Tardieu and Roussin' point out that the uses of potassium cyanide in gilding and silvering furnish fresh opportunities for cases of poisoning. Chanet attributes these for the most part to the vapors of prussic acid which thus become diffused through the work-rooms. Taylor5 also has convinced himself of the presence of vapors of prussic acid in gilding by the galvanic process. The use of Berlin blue in dye-works may give rise to poisoning by prussic acid. But all the technical cases of poison- ing by prussic acid are less productive in the way of poisoning than suicide. Amongst the poisons of vegetable origin, bitter-almond oil is the most common. It is used in the fabrication of liqueurs (Maraschino) and confectionery, and also, though less often, in perfumery. Bitter almonds, in substance like the kernels of plums and cherries, may give rise to poisoning. The officinal preparations of this group are bitter almond oil and water (U. S. Ph.), and cherry-laurel water (Br. Ph.). Except the oil of bitter almonds, none of these contain any great amount of prussic acid. Yet experience shows that they sometimes prove very deadty, particularly to children. The determination of the fatal, or even of the poisonous dose, is beset with more difficulties, and is less certain than in the case of almost any other poison. We have to contend not only with the great variety in the strengths of the officinal preparations, but also with the great volatility of the poison and other difficul- ties. It has been attempted to determine the fatal dose in vari- ous classes of animals. For human beings, however, there are no very reliable figures. According to Husemann,8 we may con- sider one grain (0.061 gramme) of anhydrous prussic acid equal 1 Gazette des Hopitaux. 1847. a Loc. cit. III. p. 83. 3 Loc. cit. p. 711. 508 BOEHM.—POISONS. to two and one-half grains (0.152 gramme) of potassium cyanide, as the smallest fatal dose for grown-up people—numbers which may at least stand as a sort of general representation of the relative poisonousness of the different forms of prussic acid. That smaller quantities may have caused death, or that larger doses may sometimes have been tolerated, appears to us to be attributable to idiosyncrasies or individual peculiarities, which cannot well be calculated, and to the difficulties in the way of determining accurately a general formula applicable to all cases. As regards the other phenomena of cases of poisoning by this acid, Ave may say that it is notable for the rapidity with which it kills, and although the accounts given of its almost lightning- like rapidity of action must not always be taken quite literally, yet after the ingestion of a large dose of the poison it commonly requires only a very few minutes to terminate life. The divi- sion into stages, adopted by most toxicologists (such as a stage of asthma, one of convulsions, one of asphyxia, one of coma, etc.), appears to us unnecessary, and rather likely to lead to false views. The duration of the whole drama is in general so brief that, however allowable in theory, any division into stages can- not be practically carried out in most cases. But experiments on animals and observations in human beings appear to us to show that even in theory any division into stages is untenable. The whole of the symptoms, from beginning to end, are the result of disordered respiratory functions, and the shades of difference between one moment and another are unfortunately so gradual and so slightly diverse that they usually glide imperceptibly one into the other Avithout any marked separation between them, and the more rapidly the larger the dose of the poison ingested. On the other hand, it does appear desirable to make a distinction between the very acute cases and the less severe forms of poison- ing, for this is a practical distinction; to the first category belong the cases described as occurring with lightning-like rapidity, and which terminate fatally in a few minutes without the sufferers being able to give any account of themselves ; whilst those cases which terminate more slowly, either in death or recovery, belong to the second class. In the first cases scarcely a minute elapses after the first tak- PRUSSIC ACID AND ALLIED SUBSTANCES. 509 ing of the poison before the symptoms of poisoning commence with sudden loss of consciousness—and in some cases the poi- soned person falls to the ground with a loud cry or shriek. It is not at all unusual for a short attack of general convulsions to supervene at this moment. This is immediately succeeded by a condition which is essentially characterized by the peculiar kind of respiration. Each breath follows the other just as has been described in experiments on animals, tediously and spasmodi- cally—the inspiration short, the expiration greatly protracted, but immediately following the short inspiration; between the expiration and the next inspiration succeeds a pause, which becomes longer every time, in which the patient, as all observers agree, lies as if dead; and, in fact, death actually occurs in one of these pauses, and simply consists in the absence of any fresh inspiration.1 The expired air in such cases is often said to have the smell of prussic acid. The eyeballs of those poisoned are strongly prominent, the pupils, as a rule, moderately dilated ; and, like the other forms of asphyxia, prussic acid poisoning is for the most part accom- panied with a good deal of salivation, which is probably the rea- son why foam covers the mouth. The jaAvs are usually some- what firmly pressed together, so that the freely secreted saliva, in the recumbent position of the body, is easily changed into foam by the spasmodic breathing. AVhilst the general surface of the skin feels cool, and is covered with cold, clammy SAA^eat, the visible mucous membranes generally sIioav a slight cyanotic tinge. The face is here and there reddened and swollen, but towards the last it is generally pale and collapsed. In the facial muscles, as well as in the extremities, slight muscular spasms occur. The sensorium is perfectly in abeyance, and even reflex 1 This peculiar respiration is a further proof of the incorrectness of Preyer's view that prussic acid poisoning commences with tetanic inspirations. Many observers of cases of poisoning in the human subject expressly call attention to the spasmodic, long- drawn expirations. We must therefore decidedly protest against a correction which Preyer himself has made in the paper of another author (loc. cit., II., p. 103), in which he accompanies the expressly mentioned " spasmodic ftrpiration," with the words in parenthesis, " should have been written inspiration." It would certainly not be difficult in this way to harmonize the observations of others with one's own opinions. 510 BOEHM.— POISONS. movements are absent. The pupils do not react with light, and there is no response to irritation of the skin. The muscles are relaxed, and no trace of voluntary movement is present. The pulse, Avhich at first is somewhat increased in frequency, becomes at a later period weak, rarely intermittent, and at the acme of the poisoning can generally no longer be felt. There are no observations of temperature in men, yet the heat of the body appears to be decidedly decreased. Urine and faeces are some- times passed involuntarily at first, and at a later stage they are suspended. In this form of poisoning death occurs within fifteen minutes after the swallowing of the poison. In less violent cases there are sometimes some subjective symptoms or complaints. The poisoned person sometimes com- plains of the bitter, somewhat burning taste of the poison, and of a feeling of constriction in the throat. With these, in the course of one or two minutes, are associated gradually increasing vertigo, palpitation, confused consciousness, obscuration of the field of vision, pain and pressure in the head, precordial anxiety, and extreme weakness of the voluntary muscles. With these symp- toms, which are usually accompanied with nausea, the poisoned person generally loses his senses, becomes devoid of sensation, and is attacked with severe general convulsions, usually epilepti- form. Yet even in this case, the convulsions usually give place to general paralysis of muscles, and then Ave generally get vari- ous modifications of the symptoms of asphyxia which have been described before, and these in longer or shorter time (from some hours to two days) end in death, or gradually, and without any special complications or sequelae, terminate in recovery. Dr. Taylor justly remarks that in those cases which recover, recovery is often preceded by vomiting. Both ructus and flatus may sometimes exhibit the smell of prussic acid. The questions, whether there is such a thing as chronic poi- soning by prussic acid ? whether this poison is cumulative % and whether the system can be at all accustomed to it % are questions which cannot be certainly answered on the basis of our present experience. The slight symptoms which follow the reception of small quantities of the poison, particularly in a gaseous form, PRUSSIC ACID AND ALLIED SUBSTANCES. 511 consist, as a rule, in some headache and stupidity, slight op- pression, threatened vertigo, lassitude, and vomiting. The sus- ceptibility of different persons to the action of the poison varies considerably. It is quite certain that the vegetable preparations of prussic acid, and the chemicals, prussic acid and potassium cyanide, perfectly resemble each other in their effects. As regards the other, venena cyanica, our toxicological experience is very slight. Ammonium and zinc cyanides appear to produce the same effects, at least qualitatively, as the substances described; whilst, as regards mercuric cyanide, it seems doubtful hoAV far its effects are due to mercury, and how far to cyanogen. The post-mortem appearances in poisoning by prussic acid are, from a pathological point of view, purely negative ; only the chemical investigation of the blood and of the viscera may sometimes succeed in obtaining traces of the poison, and in some cases the body has a remarkable odor of prussic acid all over it. No alterations of texture can be discovered, either macroscopic or microscopic ; and neither the color, properties, nor distribu- tion of the blood in the body can furnish us with any certain signs of death from prussic acid or the poisonous cyanides. Although Preyer believes that in atropine he has discovered a perfect antidote to prussic acid poisoning, yet newer experi- ments have shown us that we cannot recommend it as such. We are rather inclined, in these cases, to rely on the same mechanical aids as are applicable in other forms of asphyxia ; for the other so-called antidotes, such as ammonia, etc., are at least of doubt- ful value. After fulfilment of the causal indication, that is, the removal of or from the poison, so far as practicable, we had better proceed at once to artificial respiration, and this should be aided by all the means at our command, until respiration be re-established in its integrity. Counter-irritants to the skin and mucous membranes may be applied, as in other cases Avhere life is in danger. The injection of ammonia into a vein has lately been recommended warmly as a powerful stimulant in asphyxia, and favorable cases have been detailed as encouragements to this practice. We cannot cordially recommend this until further experiments on animals have been made. But depletory transfu- 512 BOEHM.—POISONS. sion seems likely to be of use, although it is in itself a measure so severe that it seems scarcely right to try it merely as an experi- ment in cases of real severity. SECOND DIVISION. Poisoning by other Poisonous Compounds of Carbon. CHAPTER I. POISONING BY BENZIN (BENZOL, C6H6). Benzin is obtained in large quantities by distillation from coal tar naphtha, which contains from three to four per cent, of it. At ordinary temperatures it is a colorless, highly refractive liquid, which floats on water, is very volatile, but does not boil below 80°-85° C. = 176° to 185° F. The observation that benzin is a powerful insect poison, and destroys other low forms of animal life, has led to its being em- ployed as a parasiticide in both, men and animals. Indeed, Mosler > has especially recommended it as a powerful remedy for intestinal trichinae. As the long-continued inhalation of the vapor of benzin causes symptoms of stupefaction in human beings, Simpson and Snow made experiments to see if it could be used as an anaes- thetic, but they came to the conclusion that the narcosis from benzin was not only very difficult to obtain, but AA^as associated with unpleasant symptoms—noises in the head, muscular tre- mors, and such like. Mosler and others have established the fact that benzin may be taken internally in pretty large doses (two drachms a day) without any injurious effects. In spite of 1 Berlin, klin. Wochenschrift. 1864. No. 32. NITKO-BENZIN. 513 the great use made of benzin in the arts and manufactures there has, till quite lately, been only one recorded case of poisoning by benzin—that of Perrin '—which resulted from swallowing a large quantity of benzin. The symptoms Avere those of simple narco- sis, terminating in deep sleep and final recovery. According to a verbal communication of Professor F. A. Hoffmann, there was, some years ago, a case in the Charite Hospital, at Berlin, of con- siderable interest, because it commenced Avith the symptoms of corrosive poisoning. The patient was said to have taken a large quantity (!) of benzin Avith suicidal intent, and died after some days of purulent pleurisy, Avhich originated in a perforation of the oesophagus. Unfortunately, no further details of the case could be obtained. [Sir W. Gull's case ended in recovery.] CHAPTER II. POISONING BY NITRO-BENZIN. Nitro-benzin, or nitro-benzol (f,HsN0s), is formed out of ben- zin, or benzol, when this is dissolved in concentrated nitric acid, and the solution decomposed with water. Like anilin—to pro- cure which for commercial purposes it is employed—it is a poi- son, and from a toxicological point of view is deserving of even more attention than this, because of its extensive use in factories and in the arts, which gives rise to such numerous opportunities for its injurious action on human beings. At the exhibition of 1851, in Paris, it was offered for sale, under the name of " Es- sence of Mirbane;' as harmless perfumery. It is a bright yel- low, oily sort of fluid, heavier than water, of 1.209 specific gravity, and has a very penetrating odor of bitter almonds. The taste is unpleasantly bitter, and it causes a sort of scraping or sore feel- ing in the throat. It does not mix with water, but easily mixes with alcoholic and oily fluids. To these properties it owes its uses in the adulteration of liquors, pomades, hair-oils, etc. ^ The taste is easily recognizable in very small quantities, and is far 1 L'Union med. 1861. No. 6. VOL. XVII.—33 514 BOEHM.— I'OISONS. more lasting and intense than that of bitter almond oil (essential oil of almonds), for which it has been used as a surrogate or sub- stitute, and was originally intended as such. The long persist- ence of the smell of this substance in all bodies with which it comes in contact may be explained by its very slight volatility and its high boiling point ('220° C. =428° F.). Like anilin, nitro-benzin may pass into the circulation in ani- mals in the form of vapor, and produce its effects. Its absorp- tion by mucous membranes, and by the subcutaneous connective tissue, takes place very slowly, and according to Guttmann1 not more rapidly by the latter than when applied by the mouth. However, there are no very precise observations on the absorp- tion of nitro-benzin. Bergmann* has demonstrated the extreme slowness with which it is absorbed in a liquid form. He found, after administration of three drops to a dog, that drops of this substance were present in the stomach three days after, though the dog was poisoned by it. Ollivier and Bergeron assert that they have found drops of this poison in the blood, and in the glandular organs of the animals Avhich have been poisoned by it.3 But as this has not been confirmed by any other observers we must receive it Avith great caution. The intense action of the vapors of nitro-benzin Avould rather lead us to consider that no liquid nitro-benzin gets into the blood, but that even in the stom- ach the poisonous action occurs from the vapors or fumes of the poison getting into the blood. Nothing certain is yet known as to the manner in which it is eliminated. The assertion of Dr. Letheby4 that nitro-benzin is converted into anilin in the blood, acts as anilin, and is excreted in the urine, has not been con- firmed by others, though many authors have directed especial attention to this point. We must except, however, Ollivier and Bergeron (loc. cit.), who state that they found anilin and picric acid also in all the viscera. This hypothesis of conversion into anilin must therefore remain a moot-point for the present. In its action as a poison, however, nitro-benzin behaves ex- 1 Arch. f. Anat. u. Physiologic 1866. 2 Prager Vierteljahrschrift. 1865. IV. 3 Brown-Seguard, Journal de physiol. 1863. No. XXIII. 4 Med. Chir. Review. 1863. NITRO-BENZIN. 515 actly like anilin, as a nerve-poison, whose sphere of operations is the organs of the central nervous system. Guttmann has shown that the excitability of the peripheral nerves and of the striated muscles is left intact by nitro-benzin. A single drop on bibulous paper, placed under a bell-glass and allowed to evaporate, will, in three or four hours, produce paralysis and death in frogs. The mode of death is always that of simple general paralysis without convulsions or action on the heart. In mammals, who perish by asphyxia, it is common to ob- serve convulsions of some of the muscles—as, for example, of the masseters and muscles of the fingers and toes—as well as general tonic and clonic convulsions, just as in human beings. What department of the nervous system is thus implicated neither experiments nor clinical observations have yet enabled us accu- rately to determine. It is extremely interesting to note—though as yet inexplicable—that, both in poisoning cases in men and in experiments on animals, the symptoms of poisoning are very often delayed, or in abeyance, for a period which varies from several hours to a day or more, after the taking of the poison [and even longer in some of Dr. Letheby's cases.—Trans.]. The slow absorption of the poison affords the most reasonable expla- nation. As regards the etiology of nitro-benzin poisoning, the most important source has been indicated above. The workers in ani- lin dyes, the manufacturers of these, are of course constantly exposed to danger from the handling of, and constant vicinity to, this poison. Several accidents have happened by the care- less sucking of syphons, in decanting nitro-benzin, and by the breaking of large carboys, etc., etc. The adulteration of articles of diet and beverages with the poison is a second source of danger which gives rise to cases of poisoning. Besides its use in liqueurs, essence of mirbane has been added to sweetmeats for the sake of its odor. Streeter1 gives a case in Avhich a child was poisoned by sago, to which nitro-benzin had been added. In another case two male servants were poisoned by nibbling at a pomade made with nitro-benzin. 1 Medical Times. 1854. 516 BOEHM.—POISONS. Then there is the possibility of the nitro-benzin itself being mis- taken for a beverage, especially a liqueur, on account of the smell. In this way, in the late Franco German war, according to Helbig,] eighteen soldiers were poisoned, who had found in a villa a flask containing a fluid which they mistook for a liqueur, but which the surgeon discovered to be nitro-benzin. It killed three of them. Up to the present date forty-two cases of poisoning by nitro- benzin have been placed on record ; five were females and thirty- three males ; fourteen, or one-third of all the cases, ended fatally. Exact details are wanting in four of these. Most of the cases (31) were accidental; four took place through handling the poi- son in factories where it was employed ; and three were attempts at suicide, in one of which nitro-benzin was put into the suicide's hands instead of the essential oil of bitter almonds which he intended to use. The mortality will seem yet more serious if we deduct the instance, recorded by Helbig, where several were poisoned at the same time, for then eleven out of twenty-one cases, or more than half, ended fatally. As regards the quantity of the poison taken in the individual cases we have very little precise information, and it is thus not possible to fix on a fatal dose, notwithstanding the number of cases on record. It is, however, quite certain, from a few of the cases, that very small quantities of the poison may cause death. Letheby (loc. cit.) mentions eight or nine drops as the quantity in one case. Mueller (loc. cit.) speaks of a teaspoonful, whilst Treulich2 names a thimbleful. In Bahrdt's3 case about twenty drops, in that of Ae4 two drachms, caused death. It must espe- cialby be insisted upon that even in a gaseous form this poison may cause death, and ahvays acts very energetically, but in this case it is still less easy from the nature of the case to determine the fatal dose. The symptoms of poisoning by nitro-benzin in human beings have a considerable resemblance to those of anilin poisoning, 1 Deutsche milit.-arztl. Zeitung. 1873. II. 2 Wiener med. Presse. 1870. 3 Archiv f. phys. Heilkunde. 1871. 4 Husemann, im Jahresbericht von Virchow und Hirsch. 1871. I. NITRO-BENZIN, 517 and are, like those, almost exclusively of a nervous kind. The remarkably long latent period of the symptoms has been often insisted on, particularly by Letheby and Bahrdt. Indeed, in the average of all cases, the fact was, that in general, though not quite universally, the first symptoms of poisoning did not de- velop themselves before from half an hour to two hours. But although this is not universal, and several cases have ended fatally in the course of the first eighteen to twenty-four hours after the ingestion of the poison, yet we cannot deny that the latency of the poisonous action may be a point of some practical importance in special cases as a means of diagnosis. General feelings of discomfort, weariness, nausea, and a rap- idly increasing peculiar dull benumbing of the head, are gener- ally the first complaints of those poisoned. Several observers, even in this stage, have been struck with the dirty, livid colo- ration of the skin, particularly in the face; at a later stage this reaches a high degree of cyanosis. Spontaneous vomiting sometimes occurs. With increasing feelings of anxiety, want of breath, incapacity for clear thinking, and more and more confu- sion of the sensorium, the true narcotic symptoms are now more or less quickly developed. These sometimes assume the charac- ter of irritant symptoms, sometimes they are more paralytic. It is very frequently mentioned in the accounts given of poisoning by nitro-benzin that there were severe general convulsions and contractions of particular muscular groups ; in some few cases, indeed, trismus and tetanus have been noted.1 At the height of the poisoning consciousness is generally quite lost, as well as sensation and reflex irritability. The pupils are dilated, but, as a rule, they still act, though feebly. Some observers, as B. Kreuser, have noted contracted pupils. Bahrdt and Kreuser observed continual rotary spasms of the ocular muscles. The external integuments show charac- teristic colorations. The face has sometimes been described as bluish-gray, sometimes as ashy-colored; the lips as purplish- red, and the fingers as bluish-black. 1 Compare Schenk (loc. cit.), Kreuser (Wiirtbg. Corr.-Bl. 1867), Ewald (Berlin klin. Wochenschr. 1875. No. 1). 518 BOEHM. —POISONS. Pulse, respirations, and temperature present their usual char- acters in such conditions, and offer no special characteristics. Either a convulsive or a comatose stage precedes death by asphyxia. As a rule, any localized symptoms of irritation are absent, except vomiting, pains in the abdomen, and a feeling of irrita- tion, like scraping, in the throat, of which those who swallow the poison sometimes complain. Letheby and Schenk have noticed that the tongue is swollen, and of a whitish color. The vomited matters, as well as the breath, always smell strongly of the poison, and thus render the diagnosis easy to those who can distinguish the smell from that of prussic acid, which is not diffi- cult Avhen once learned. Ewald states that he has lately 1 discovered sugar in the urine of these cases. The cases which do not end fatally are generally protracted by considerable disturbance of the general health succeeding the poisoning. Want of appetite, muscular weak- ness, headache, noises in the ears, and a sense of oppression (Eingenommenheit) are the principal inconveniences met with. No permanent pathological changes occur. The results of all the post-mortem examinations made as yet have been so far negative, inasmuch as no changes have ever been discovered in the organs of the body which could in themselves establish the fact of the poisoning. The only reliable fact, there- fore, is the scarcely ever absent smell of the poison, which for a long time closely adheres to the whole body of the poisoned per- son, and especially pervades the internal organs. This durability of the smell of nitro-benzin serves as a characteristic, by which we may distinguish it from the somewhat similar, but more tran- sient smell of prussic acid. As the residue of a moderate amount of irritation during life, we sometimes find catarrhal swelling and redness of the digestive tract, and occasionally, also, ecchy- moses in the mucous membranes. Having regard to the slowness with which nitro-benzin is absorbed, it will always be proper to begin the treatment of a case of poisoning by nitro-benzin by endeavors to remove any of 1 Med. CentraM. 1874, u. loc. cit. ANILIN AND ANILIN DYES. 519 the poison which may remetin in the stomach. Whether emetics or the stoma elt-pump should be used must depend upon the particular case. If this indication be fulfilled, the rest of the treatment must depend upon the symptoms. That particular attention should be paid to pulse and respiration is easily to be understood. If the respiration be much interfered with, the use of artificial respiration may be essential. There is as yet no known rational antidotal treatment against nitro-benzin poisoning. CHAPTER III. POISONING BY ANILIN AND ANILIN DYES. The substance called anilin rtr6H7N), which may be called the mother-dye of all those beautiful coloring matters which play so important a part in modern industry, is an organic base, which unites with acids to form crystalline salts. It is obtained in large quantities from nitro-benzin, and in a chemically pure state is a colorless, oily sort of fluid, of peculiar smell, and of burning, bitter taste. Its reaction to test-paper is neutral; air and light gradually turn it yellow, and even at ordinary temperatures it gives off copious vapors, which can be recognized at once by their smell, which is characteristic. No one, nowadays, doubts the poisonous nature of anilin, both as regards the free base and its salts, since, on the one hand, practical medicine has had to do with many indubitable cases of anilin poisoning; and, on the other hand, toxicologists have proved its poisonous proper- ties by numerous experiments on animals. As regards anilin dyes, however, the case is somewhat different. We cannot gene- ralize as to their being poisonous or not, but each must be sepa- rately dealt with. It is not possible here to go into great detail on this point, but we may mention that the injuriousness of the colors is, as a rule, due to admixtures, which are sometimes sub- stances used to oxidize the anilin (arsenic acid, for example), whilst sometimes it depends upon undecomposed anilin (the parent-dye) being present. We can only consider the latter 520 HO KH AC--POISON'S. cause now. It is, to say the least, doubtful if any of the anilin colors are poisonous in and by themselves alone. The innocuousness of the well-known anilin colors, known under the names of fuchsin, azalein, Magenta red, etc., etc.," has been put beyond question by the in- vestigations of Sonnenkalb * and Bergmann.3 The cases of poisoning which have, notwithstanding, been due to the colors above named — as, for example, one observed by Bergmann himself—must be attributed to an admixture of undecom- posed anilin.4 The same holds good as regards corallin or paeonin, a red color composed of rosolic acid, to which Tardieu5 ascribed very poisonous properties. Its harmless- ness in a chemically pure condition, Landrin6 and Guyot' have demonstrated. The rosolic acid, which in itself is harmless, is often, as Eulenberg and Vohl and Guyot found, adulterated or not freed from carbolic acid. This explains the appa- rent contradiction between Tardieu's observations, and the local diseases which are observed to be caused by the use of articles of clothing colored with corallin. There are a good many of these cases, well authenticated, but we cannot consider them here at any length. For the most part, they consist of eczematous or papular skin-diseases, in consequence of the wearing of colored socks, or hosiery dyed with corallin, or the use of red flannel shirts. In some of the cases, this is due to the arsenic contained in the red colors. The poisonous symptoms produced by certain green aniline colors, since they were caused by the presence of arsenic, will also be considered in another part of this volume. Free anilin may, by means of its volatility, get into the circu- lation, not only by way of the stomach, but also through the lungs; whether it can pass through the skin also has not been settled. Lailler's8 two cases, in which after the external appli- cation of muriate of anilin in psoriasis, there were symptoms of anilin poisoning, do not, as we believe, prove that the uninjured skin can absorb free analin. Authors differ from one another as to the way in which it is eliminated from the animal system. Bergmann (loc. cit.) recovered it from the urine, which Schuch- 1 These are salts of a basic substance, called rosanilin, which is itself colorless, or only faintly reddish. This itself is not at all poisonous. It is formed by oxidation from anilin and toluidin. 2 Anilin und Anilinfarben. Leipzig. 1864. 3 Prager Vierteljahrschrift. 1865. IV. 4 See Eulenberg and Vohl, Arch. d. Pharmak. 1870. September. 5 Comptes rend. LXVIII. 1869. 7 Ibid LXIX' p 388 6 Ibid- LXVIIL P- 15^. • L'Union med. 1873. No. 67. ANILIN AND ANILIN DVES. 521 hard1 (loc. cit.) and Sonnenkalb (loc. cit.) failed to do; these assert that the poison is excreted by the lungs. As regards the further changes undergone by anilin in the blood, nothing defi- nite is known. Bergmann alludes to Turnbull's2 view, that anilin is oxidized in the body to violet coloring matters—founded on the cyanotic coloration of the skin noticed in cases of poison- ing—without confirming it. Besides its general action on the blood, anilin in a free state has a slight local action on the parts to which it is applied, and this clearly finds its explanation in the behavior of the free base when present in solutions of albu- men, which are coagulated by this poison. If large quantities come into contact with mucous membranes, it may prove the exciting cause of gastro-intestinal symptoms. Bergmann only attributes very slight local irritant effects to this poison ; in ani- mals who took it some time he only noticed catarrh of the gastric mucous membrane, and he never noticed any abscesses after re- peated injections into the subcutaneous connective tissue. But the changes produced in the mass of the blood in consequence of this poison are far more serious. These have the general character of narcotic poisoning, and are limited to the functions of the central nervous system. The experiments of Schuchhard, Bergmann, and Sonnenkalb leave no doubt on the point that, both in cold- and warm-blooded animals, this poison acts like other narcotics, by altering the functions of the brain and spinal cord. Muscular contractions and general convulsions, anaesthesia, and paralysis of motion, are the symptoms thus caused. The excitability of the peri- pheral motor nerves, as well as of the muscles, remains intact. The action of the heart is only disturbed in a secondary manner, that is, in consequence of the affection of the muscles concerned in respiration and the defective aeration of the blood, induced by their paralysis. Experiments on frogs show that anilin is not a poison to the heart. The question, whether anilin exerts any special or specific influence on the nervous centres for breath- ing movements, has not yet been solved by any experiments which have yet been made, although they have proved that 1 Virch. Archiv. Bd. XX. 2 Lancet. 1861. o22 BOEHM.—POISONS. anilin death, in warm-blooded animals, happens through as- phyxia. The opinion of some French authors,' that the symptoms of anilin poisoning are caused by the changes produced in the blood by the poison, and not by direct action on the nervous cen- tres, has not been confirmed ; and the observations on Avhich this hypothesis was founded, namely, the want of coagulation of the blood in anilin poisoning, and peculiar changes in the red blood- corpuscles, have proved to be erroneous. The manufacture of anilin and of anilin colors affords the chief, and fortunately the only, facilities for cases of poison- ing. The workers in such factories are most exposed to this danger. But cases of poisoning also occur, as Bergmann's case shows, with the red and violet (mauve) anilin colors, which sometimes contain large quantities of undecomposed anilin ;— but generally only Avhen, through some unlucky accident, large quantities of the poison get into the stomach. The medicinal use of anilin salts for epilepsy and other diseases, although as yet not very largely employed, has, so far as we know, given rise to no cases of poisoning. But the external use of hydrochlorate of anilin in two cases of psoriasis gave rise to poisoning, accord- ing to Lai Her (loc. cit.). We are decidedly of opinion that the affections caused by wearing articles dyed with anilin colors next the skin are not really properly attributable to anilin poisoning. The number of cases of pure anilin poisoning as yet placed on record is very small. No trustworthy figures can be given as regards the poisonous or fatal dose of anilin in human beings. Acute anilin poisoning is preceded in human beings by toler- ably characteristic external symptoms, and all the cases hitherto published show a remarkable agreement in their principal fea- tures. The period at which the symptoms of poisoning begin varies, as it appears, according to the quantity of the poison taken and the mode of its ingestion. Whilst in some cases more than half an hour elapsed after the breathing in of the anilin vapors 1 Ollivier and Bergeron, Brown-Sequard, Journ. de Physiologic VI. ANILIN AND ANILIN DYES. 523 before any symptoms of poisoning occurred, the action of the poison in one of the cases described by Mackenzie was extremely sudden. It was the case of a young man who was cleaning out an anilin vat, and was affected by the vapors ; he was taken out of the vat in a half-conscious state.1 In the case also of Knagges,2 in which a workman broke a carboy of anilin, the symptoms of poisoning set in whilst the man was wiping it up with cloths. How long it takes for the poison to act when swallowed has not been determined with any certainty from the observations hitherto made. In Lailler's cases the general symptoms occurred in one and a half and four hours respectively after the applica- tion of the muriate of anilin to the skin. The first symptoms consist in oppression in the head, nausea, vertigo, and headache. Lailler often observed vomiting. Gradu- ally a sense of suffocation, and difficulty of breathing, with simultaneous somnolence, which in Mackenzie's case went on to loss of consciousness, occur—whilst Bergmann's patients retained their consciousness all the while. Pains in the extremities, and muscular weakness, with fibrillary cramps or convulsions, and anaesthesia of the skin, have been noted by almost all observers. Amongst the objective symptoms, one of the most remarkable is the peculiar dark cj^anotic coloring of the mucous membranes of the nose, ears, and nails. The rest of the skin shows a livid, bluish-gray coloration, and a lowered temperature. The pupils are not generally much affected. The pulse and respiration are quickened at first; the former at a later period grows slower, and is easily compressible. The breathing is labored and dyspnoeal. General convulsions have not as yet been noted in human beings. All these symptoms generally vanish in the course of one, or at the most tvvo days, without leaving behind them any very special disorders. Up to the present date, no case has ended fatally. In the case of poisoning by anilin dyes, traces of these are found in the cavity of the mouth, in vomited matters, in the faeces, and in the urine, which in Bergmann's case was colored 1 Med. Times and Gaz. 1862. March, p. 239. Fletcher's case, quoted by Mackenzie in the same article, was not, as Hwemann (Toxikologie. Sptb. p. 114) wrongly states, one of anilin, but of nitro-benzol poisoning. 2 Med. Times and Gazette. !861. I. 583. 524 BOEHM.—POISONS. bright red. Anilin itself is easily recognizable by its smell. Only Charvetl has described chronic poisoning by anilin. There were general nervous symptoms, vertigo, stupidity, muscular cramps and muscular weakness in the extremities, hyperesthe- sia, anaesthesia, and neuralgic pains, which occurred epidemically along with gastric symptoms, amongst the working-people of the factory at Pierre-Benite ; and these symptoms all disappeared on removal from the poisonous atmosphere, without any further treatment. The workers in anilin factories are said frequently to suf- fer from obstinate bronchitis, and they therefore guard against breathing in the vapors by keeping a damp towel in front of the mouth. As regards the treatment of anilin poisoning, in the absence of special clinical experience on the point, and from the fact of no true antidote being known, we cannot lay down any special rules. Our treatment must be guided by the same principles which regulate that of other cases of narcotic poisoning. CHAPTER IV. POISONING BY CARBOLIC ACID (06H60 ; PHENILIC ACID, HYDRATE OF PHENYL). Carbolic acid, one of the products of distillation from the coal-tar naphtha, so largely obtained in the preparation of gas for the purpose of lighting, has during the last thirty years attained great importance both as an article of commerce, as a medicine, and as a poison. The crude carbolic acid (often con- founded with officinal creasote) is a brownish-red fluid, of the consistence of a thin syrup, of a penetrating, characteristic odor, and of a burning and highly unpleasant taste. But, of late more especially, crystallized carbolic acid is met with which occurs in colorless shining needles, which in large quantities have a faint 1 Annales d'hygiene publ. Oct. 1863. CARBOLIC ACID. 525 pink tinge, and have almost the same kind of strong empyreu- matic unpleasant smell, though perhaps not quite so offensive as the crude acid. Both preparations are officinal. Even coal- tar naphtha itself (the oleum lithantracis of the pharmacopoeias) deserves to be mentioned here, inasmuch as its medicinal, hygie- nic, and economic uses may sometimes give rise to cases of poi- soning. Carbolic acid as a poison, as a disinfectant, and as a medicine and surgical appliance, has been the subject of several treatises and of much study and experiment. We must confine ourselves here to the investigations on its action as a poison. Carbolic acid acts locally as well as generally. The local action is prob- ably due to the strong affinity possessed by this substance for the constituents of the animal body, which is true, whether (in a concentrated condition) it simply abstracts water from the tissues, or whether it actually enters into combination with al- buminous bodies. Five per cent, solutions of carbolic acid pre- cipitate albumen, though Bill' states that the two substances are not chemically combined in this precipitation. Where the poison comes in contact with the surface of the skin, or of mucous membranes, a white scab forms, the thickness of which depends on the concentration of the acid. These effects are very similar to those of the weaker acids and other metallic caustics, and do not, therefore, need prolonged discussion. The general effects of carbolic acid are dependent on its absorption into the blood. This absorption may occur in all the ways in which solutions are capable of being absorbed, and it would also seem as if the general action of carbolic acid may follow the breathing of air strongly impregnated with its fumes. Opinions differ as to the removal and elimination of the sub- stance from the fluids of the tissues (Saftemasse). There is no doubt that many observers have detected carbolic acid in the urine of animals and men poisoned by it. Hoppe-Seyler2 also found it in the blood and internal organs of poisoned dogs. Lemaire's3 statement, that carbolic acid occurs in the expired 1 See Virchow and Hirsch, Jahresbericht. 1872. I. p. 371. 2 Pflueger's Archiv. V. 1872. 3 De l'acide phenique, etc. Paris. 1865. 526 BOEHM. —POISONS. air (of such cases), has not been confirmed by later researches, nor could Bill (loc. cit.) demonstrate it in the perspiration or in the faeces. From all this Ave may certainly conclude that a part of the poison introduced passes out again without suffering decomposition. Other observations render it also tolerably cer- tain that some decomposition of this substance occurs in the blood, although we must consider Hoffmann's1 view, that it undergoes complete combustion in the blood, as not established. The dark-green, and often almost black color of the urine after standing some time, which often occurs when this poison is absorbed from the surface of a wound, is strikingly characteristic. It is seldom seen when the poison is taken internally. This symptom clearly depends on the presence in the urine of some product of decomposition of carbolic acid, the chemical nature of which has not been discovered. E. Salkowsky,2 in comment- ing on this striking fact, inclines to the opinion that the decom- position occurs before the absorption of the carbolic acid, as it so rarely occurs from the internal use of this substance. This author believes most of the carbolic acid, applied either internally or externally, must be decomposed, because the quantities which can be demonstrated in the urine are always extremely small. The antiseptic qualities of carbolic acid only interest the toxicol- ogist inasmuch as they demonstrate the poisonous character of carbolic acid as regards lowly organisms of both animal and vegetable origin. Husemann and Ummethun,3 and E. Salkowsky, have care- fully investigated the general symptoms of poisoning which follow the absorption of this poison in both men and animals— the two former experimentally, the latter by the observation of a number of poisoning cases in the human subject. It must be premised that there is a very considerable discrepancy between the action of this poison on animals and in human beings. In the former there occur unmistakable symptoms of irritation of the medulla oblongata and of the spinal cord, which have as yet never been witnessed in human beings. 1 Beitrage zur Kenntmss der physiologischen AVirkungen der Carbolsaure und des Oamphers. Inaug.-Dissert. Dorpat. 1866. ' Pflueger's Archiv. V. 1872. a Deutsche Klinik. 1870, 1871. CARBOLIC ACID. 527 These irritant phenomena partly concern the respiratory cen- tres, and partly those for reflex action in the spinal cord. In frogs, E. Salkowsky observed, some time after the poisoning, consecutive to a stage of more or less paresis, clonic convulsions in the extremities, occurring and gradually increasing in severity, like those in strychnine poisoning, lasting for hours at a time. He also verified analogous affections in rabbits, in which what at first were only general muscular tremors, became general con- vulsions. Salkowsky refers the origin of these spasms to the spinal cord—their occurrence in various animals is confirmed by Husemann and Ummethun. These convulsions still happened when the brain and the prolongations of the spinal cord (medulla, etc.) were severed (by section) from the spinal cord itself, and also when the arteries conveying blood to the limbs were liga- tured. It could not, therefore, be said that the convulsions were due to asphyxia. The disorders of respiration consist in a very considerable increase of the frequency of breathing, and in its becoming very superficial. Fatal doses bring on dyspnoea at the last, and manifestly lead to death by paralysis of respiration. The first acceleration of respiration is not entirely prevented by section of the vagus, although this operation is of unmistakable efficacy. On the other hand, carbolic acid is able to increase the number of respirations in an animal Avhose vagi have been previously divided. Salkowsky therefore believes that this poison not only affects the respiratory nerve-centres, but also excites the pulmo- nary terminations of the vagus. The organs of circulation are less affected by carbolic acid. The frequency of the beats in the frog's heart gradually diminishes to about half, whilst the con- vulsions go on increasing. We shall return to the symptoms in human beings by and by. The gastro-intestinal symptoms produced by the local action of the poison in the stomach and bowels do not need any minute description. In the intensity of its action, carbolic acid belongs to the strong poisons, though not to the very strongest of all. On an average several decigrammes (a decigramme=H grain nearly) are required to kill even very small animals, so that this poison 528 BOEHM. —POISONS. is considerably inferior in strength to the more violent alkaloids, to prussic acid, to sulphuretted hydrogen, and to the corrosive mineral poisons. As regards the susceptibility of various classes of animals, and the poisonous and fatal doses in each class, we must refer to the often-quoted monographs of Lemaire, Husemann, Ummethun, Salkowsky, and others. The very varied uses of carbolic acid, both in medicine and surgery, and its economic and hygienic uses of late years, have given rise to a large number of poisoning cases in human beings. The cases hitherto observed, therefore, belong partly to the domain of economic or technical poisonings, partly to so-called medici- nal ones, and in some few cases it has been taken with suicidal intent. Most of the medicinal cases have arisen from the use of carbolic acid as an external application, either for skin-diseases (as, for example, scabies, etc.)—in which it was rubbed into the uninjured skin (cases by Koehler and Machin)—or by its appli- cation when insufficiently diluted to open wounds, suppurating surfaces, and abscesses. Sandwell also states that water-closets in which it has been used for disinfection, when they have been imperfectly cleansed, have given rise to symptoms of poisoning —chiefly consisting of pains in the gluteal region. Very severe symptoms were caused in two cases (those of Pinkham and Michaelis), through clysters of carbolic acid used against intes- tinal worms—and these confirm the statements of Husemann and Ummethun, that in their experiments on animals the poisonous action occurred very rapidly when the poison was applied to the rectum. England has furnished by far the largest number of cases: 26 out of 33 such cases recorded were in England, and only 7 in Germany, France, and Switzerland ; 21 were in males, 10 in females ; 26 ended fatally, and 7 recovered; 2 only were cases of suicide ; 11 of medicinal application ; in 20 an accident was the cause. The poison was taken internally in 22 cases, whilst in 9 the symptoms f olloAved its external application. Chil- dren exhibited a great degree of sensitiveness to the poison ; but in this, too, individual peculiarities played a part. The poison naturally acts with more rapidity and energy on an empty stom- ach than on a full one. CARBOLIC ACID. 529 As regards the fatal dose, we cannot fix any definite limits. In applications to the skin, very severe symptoms have occasion- ally resulted from relatively very small quantities of the poison. As regards internal use, Husemann considers eight grains as a dangerous dose. In most of the cases of poisoning it is not easy to fix the quantity of the poison very definitely. The doses determined as poisonous in animals are, it is easy to understand, not applicable to the case of human beings. From the cases of poisoning by carbolic acid which have been recorded, we select the following as being those in which the fatal dose and other circumstances are pretty accurately re- corded : Observer. Subject of Poisoning. Dose. Result. Jeffreys & Hainworth Ogston. Zimm. Wiltshire. Harley. Sutton. Pinkham. Way, J. Brabant. Russel. George. Man aged 56. " 47. A soldier. Typhus patient (get. 19). Man aged 47. " 43. Child aged l£. Woman aged 35. " 44. Girl aged 10. ? I i.-ii. 30-40 grm.= 465to620grs. §ss. § i-li-2 teaspoon-fuls. 1 viii. Si. §8S. Death after 50 minutes. " 18 hours. " 60 " " 2 days. " 5£ hours. " 12 Died suddenly. Death after 50 minutes, 85 " " 30 " An ounce of concentrated carbolic acid may, therefore, under all circumstances, be regarded as a very dangerous, if not abso- lutely fatal dose, although we cannot dare to say that even smaller quantities (e. g., one tablespoonful or half an ounce) may not produce fatal symptoms. The results of this inquiry are approximatively accurate, and enable us rather to say what will, than what will not, be likely to prove fatal. The symptoms of poisoning by carbolic acid in human beings offer the following characteristic features. In acute poisoning, with large quantities of the poison, loss of consciousness and of voluntary movements sets in, as a rule, in a very few minutes. Those poisoned sink into a comatose condition, in which gene- rally sensibility and reflex movements are completely abolished. VOL. XVII—34 530 BOEHM.—POISONS. The breathing is described as stertorous by most observers, or, if consciousness is not entirely lost, as very laborious and dysp- noeal. Well marked general convulsions, up to the date of this, have never been developed in human beings, but are scarcely ever absent in experiments on animals. Death succeeds and terminates this comatose condition without any other very striking symptoms. We find a high degree of contraction of the pupils, which are insensible to light, noticed as an almost constant symptom. The skin is cool, covered with sweat, and exhibits a livid color. Urine and faeces are obstinately sup- pressed. Vomiting is one of the most constant symptoms, and occurs principally, it seems, at the beginning of the poisoning. In the earlier stages of the poisoning, the pulse is generally strikingly slow; later on it is generally much quickened. The repeated filling of the mouth with foam, observed in Jeffreys' and Hain- worth's cases, may be ascribed to salivation, which has been observed in most cases of poisons which kill by asphyxia. We have already noted the condition of the urine sometimes met with—and although this dark coloration is due, as a rule, to the external application, yet it does undoubtedly occur in cases of poisoning by the internal use of carbolic acid also, as is indu- bitably proved by the cases of Ogston, Zimm, Wiltshire, and Fer- rier. It might therefore be well, in all doubtful cases of carbolic acid poisoning, accompanied with retention of urine, to use the catheter as a means of diagnosis. Albuminuria has occasionally been noted, but is not a constant symptom of poisoning by car- bolic acid. In a few cases it has been accompanied with pains in the region of the kidneys. The local action of the poison is often very manifest, when it is swallowed; for, immediately after the poisoning, it is common for violent pains to occur in the course of the oesophagus, below the sternum, and in the region of the stomach. The vomiting also which occurs in an early stage may be attributed to the local irritation, though it is right to mention that it also occurs in cases of poisoning by the exter- nal application of comparatively small quantities of the poison. The nervous symptoms which succeed render any special exten sion of these pains in the stomach and abdomen impossible. CARBOLIC ACID. 531 The whitish coloration of the mucous membrane of the mouth and throat, and the scabs or crusts due to the caustic action in the neighborhood of the mouth, or on other parts of the skin, may serve as aids to diagnosis. In less severe cases of poison- ing by carbolic acid, those affected complain of headache, ver- tigo, nausea, want of appetite, and other similar, but little characteristic phenomena. Zimm's case shows in a very striking manner that in this sort of poisoning, particularly in a state of coma, and of total reflex paresis, it is very easy for part of the poison to get into the air-passages; no doubt in this case the frequent vomiting led to this unpleasant complication. The autopsy in this case revealed double pneumonia. The peculiar urine and the firm adhesion of the peculiar and not easily mistaken smell of carbolic acid to the clothes and person of the poisoned must be regarded as diagnostic points of considerable importance in cases which might be otherwise doubtful. Carbolic acid poisoning, particularly when large quantities are taken, usually runs a very rapid course, and is very rarely protracted. All the hitherto noticed fatal cases have proved so in the course of the first twelve hours—some, indeed, after only a few minutes. Even when recovery occurs this is usually sud- den, and without leaving behind it any remarkable disorders or noteworthy complications. As regards the results of anatomico-pathological (post-mortem) investigation, we must again lay special stress on the smell of carbolic acid, which pervades and adheres to the contents of the digestive canal, the glandular organs and their secretions (urine), and in cases of poisoning by a large dose is hardly ever absent. The remaining changes offer nothing very remarkable. We can scarcely lay much stress on that quality of the blood on which Husemann so insists, viz., that it is very thin and dark-colored, and coagulates badly—at least as regards human beings. Apart from the very precarious and doubtful nature of the symptom itself, it does not appear that, in cases of poisoning by carbolic acid in human beings, the quality of the blood has been at all uniform. Indeed, in several of the recorded accounts of post- mortems, we find express mention of extensive clots in the heart 532 BOEHM. —POISONS. and large vessels (Ogston, Zimm). The appearances on the mucous membranes of the digestive organs are of far more im- portance—the whitish color, the hardness of the epithelial coat- ing, and the loss of substance—but they are such as occur also in cases of poisoning by other dilute acids. A black color of the kidney, after long exposure to the air, has only been noted in one case (Barlow's) in the human subject, and has been found in animals by Husemann, although not constantly. As regards the treatment of carbolic acid poisoning, we have very little clinical experience of a useful kind to guide us. The stomach-pump was used with considerable success in one case by Mosler; and there can be no doubt that it may be useful in other cases for the removal of large quantities of the poison from the stomach, if its use is not counter-indicated by a suspicion of strong corrosion or erosion of the stomach. Husemann and Um- methun have instituted numerous experiments in order to dis- cover antidotes, and after proving that a number of substances (glycerine, oils, alkalies, etc.) are useless, saccharated lime (cal- caria saccharata) proved to be the substance which most nearly corresponded to the requirements of a chemical antidote for carbolic acid. The compound of lime and carbolic acid is easily soluble and not poisonous. The use of lime-water itself is not practicable, on account of the great quantity required in order to neutralize the carbolic acid in any given case of poisoning. Of course the antidote is only applicable in cases of poisoning by the internal use of carbolic acid. The saccharated lime may easily be given in watery solution, or, if needs be, by an oesopha- geal tube. Whenever possible, this procedure should always precede the application of the stomach-pump. The nervous symptoms in carbolic acid poisoning may also necessitate a symptomatic treatment; thus, in extreme coma, cutaneous irritants, artificial respiration, electricity, and all the other aids and appliances recommended in other cases of narcosis. NITRO-GLYCERINE. 533 CHAPTER V. POISONING BY NITRO-GLYCERINE. The substance known as blasting-oil (Sprengol), nitro-glycer- ine or glondin (C3H503(NOa)3), is an oily, very slightly volatile, but extremely explosive liquid, which is shown by numerous experiments, agreeing with one another, to be a poison, both to various classes of animals and also to human beings. But, so far as we know from the experimental and other cases of poison- ing which have occurred, its action as a poison is far more in- tense in animals than in the human subject. As cases of poisoning by nitro-glycerine are excessively rare, we shall not discuss the very copious materials collected with so much care by Husemann,' but the following observations may serve as a practical guide: Nitro-glycerine is very slightly soluble in water (only 0.25 per cent., according to Nystroem). Its poisonous effects succeed its introduction into the mouth, as well as its application to the sound skin. As regards its elimination and its behavior in the system, nothing very precise is known. It has been supposed that nitro-glycerine leads to the formation of nitrogen monoxide (Stickoxydul) in the blood (Onsum'), or even prussic acid (Nys- troem3), and that its poisonous action is due to some such decom- position. The effects of nitro-glycerine on frogs consist in tetanic con- vulsions, followed by general paralysis. Even mammals get convulsions, besides dyspnoea, quickened pulse, mydriasis, and general paralysis. In frogs no convulsions occur if the cerebrum be removed previous to the poisoning. In human beings it appears that very small doses of nitro- glycerine cause severe and long-persistent headaches, associated with an unpleasant knocking or hammering in the temporal regions, considerably increased by any movements of the head. 1 Schmidt's Jahrbiicher. 1866. 2 Quoted by Husemann, loc. cit. 3 Reference as before. £34 BOEHM. —POISONS. Heaviness in the head, clouds before the eyes, vertigo, quicken- ing of the pulse, and palpitation, and a feeling of heat in the face have been noted as special symptoms of poisoning. Larger doses are said to cause dyspnoea, oppression in the chest, lassi- tude, muscular weakness, and stiffness in the muscles of the jaw. Onsum1 lost consciousness after a dose of ten drops of nitro-glycerine ; on awaking out of this unconsciousness there occurred severe headache, and general muscular tremors. There were no true convulsions. Nitro-glycerine also has a local action. When swallowed it causes burning in the throat, pains in the epigastrium, hiccough, nausea, vomiting, and sometimes colicky pains, with diarrhoea. The great majority of cases of poisoning by nitro-glycerine terminated favorably, although considerable alarm was felt at first on account of symptoms such as general paralysis being present. Yet it is usual for severe headache to be left for several days. In one of Husemann's2 cases the general paralysis lasted till the evening of the next day. According to Nystroem, three fatal cases of poisoning by nitro-glycerine have occurred in Swe- den. Death without convulsions succeeded severe dyspnoea, with cyanosis in the condition of coma. Hyperaemia of the cranial contents was found at the autopsy. The clinical materials being so scanty, it is not easy to lay down rules for the treatment of poisoning by nitro glycerine. Morphia is without any action as regards the relief of the headache caused by this poison. There is as yet no known antidote. Accordingly the treatment, at present, must be purely expectant or symptomatic. 1 Loc. cit. 2 Deutsche Klinik. 1867. 18,19. THIRD PART. Poisoning by Tainted Articles of Diet. CHAPTER I. SAUSAGE-POISONING. BOTULISMUS. ALLANTIASIS. Amongst the maladies which owe their origin to the use of articles of nourishment from the animal kingdom which are undergoing decomposition, there are some which are designated as cases of poisoning, and studied by toxicologists on account of their peculiar and sharply defined symptoms, which are in part those of narcosis, and on account of their singular and generally fatal course and termination. Yet it is no more pos- sible now than it was eighty years ago to discover any specific poison in such cases, or to accurately determine the chemical nature of the poison supposed to be present. All the numerous hypotheses and suspicions, both of former times and of more recent date, as to the nature of this poison, have, one after another, been proved erroneous. It must be clearly understood that the existence of any pre- formed poison in the foods which cause the illness is itself, as yet, only an hypothesis; for, on the one hand, we cannot quite dismiss the hypothesis that lower organisms of a fungoid nature may be implicated in the causation of the malady ; whilst, on the other hand, there is a strong suspicion that the injurious sub- stance which acts as a poison may be developed for the first time within the human body out of the tainted meat. And, unfortu- nately, the darkness which thus invests the whole subject cannot be. cleared up by experiments on animals, for the door of research 536 BOEHM. —POISONS. in this direction seems barred by the fact that the substances concerned only appear to cause morbid symptoms in human beings, and can be partaken of by the animals generally used in toxicological researches (dogs, cats, etc.) without their suffering any inconveniences. The study of the true nature of sausage- poisoning, and of the opinions which have been formed upon it, is so far of interest as exhibiting the present standpoint of our chemical knowledge and of pathological opinion. The subject is exhaustively and elaborately discussed in "Husemann's Toxi- kologie," and also by Mueller, in a recent resume of all that relates to sausage-poisoning and the like,1 to which we refer for details. Only the leading features can be indicated here. As chemical analysis has, in a large number of the cases, most positively settled the fact that no metallic poisons, such as arsenic, copper, or the like, were present, these could not be the real cause of the sausage-poisoning. We are therefore driven to look for the true cause of the poisoning in the organic substances of which they were composed. As these comprise a great variety of different kinds of meat and fats, sometimes smoked or cured, and sometimes not so treated—blood, liver, bacon, pork, etc., etc. —and as all and each of these have produced symptoms which are practically identical, and only differ in the intensity of the symptoms, the opinion that processes of decomposition, or the products of decay, are the true cause of the symptoms, has become accepted as very probable. But since the ordinary pro- ducts of animal decay do not produce the same specific action in human beings, there has been started a fresh hypothesis of a "modified or peculiar putridity" to account for the action of the sausage-poison; an hypothesis which may serve at least a temporary purpose. The literature of sausage-poisoning does not date any further back than the first ten years of the present century; and general attention was first attracted to it by the exhaustive works of Justinus Kerner3 on the remarkable disease caused by this poison. We owe to him a good account of the earlier cases. Kerner believed that all the symptoms were due to a " fatty acid," which he considered the active poison ] Deutsche Klinik. 1869, 1870. 8 Neue Beobachtungen, etc. Tubingen, 1820; und Das Fettgift. Tubingen, 1822. SAUSAGE-POISONING. 537 in the sausages, and he made a number of experiments on dogs and other animals, in which it would appear that the fatty acid artificially prepared by him excited symptoms similar to those caused by the poisonous sausage. Unfortunately, how- ever, the reading of this lecture makes one suspect that Kerner frequently intro- duced his poison :nto the larynx, and thus produced the aphonia which he con- sidered a pathognomonic symptom of the sausage-poisoning. But authors long entertained the opinion, founded on the acid reaction of the poisonous foods, that they contained a poisonous acid, combined with some volatile substance. This opinion was first shown to be incorrect by Schlossberger,1 who suspected rather that organic bases were present in the sausage-poison. Hoppe-Seyler, however, the last chemist who has analyzed a poisonous sausage, failed in demonstrating any organic bases in it, and accordingly, at the present moment, the results of all chemical investigations into the sausage-poison are purely negative. And as nothing positive can be said as to the nature of the poison, except that it is very probably the result of slow putre- faction of animal substances, so also the true nature of the poi- sonous process, the pathology of it, is also highly obscure, dif- fers widely from all other kinds of poisoning, and cannot well be compared with any of them. It appears to us to be characterized by the tedious course of the poisoning, extending over many days, and sometimes weeks ; and that these point to processes going on in the blood, which do not occur in other kinds of poisoning, in which we simply have to do with the absorption and elimination of a foreign body from the system. Although symptoms of disorders of the digestive tract are scarcely ever absent, yet the whole disease does not at all resemble a simple attack of gastro-enteritis. And the results of post-mortem investigation in cases of sausage-poisoning forbid our entertaining the opinion that the injurious agent has a local action analogous to that of other irritant and corrosive sub- stances. So also in the domain of the nervous system, the symp- toms are just as little comparable with those of pure narcotic poisons, if we take them in their totality, and not separately, and especially if we regard the long persistence which they exhibit in so striking a manner. There are some of the symp- toms which make us suspect that a lasting change in the nutri- tion of the nerve-centres occurs, just as in diabetes mellitus, for example. And just in the same way the disorders of the gene- 1 Archiv fiir phys. Heilkunde. 1853. 538 BOEHM.—POISONS. ral health, the persistent anomalies of nutrition which have been observed in the stage of convalescence, indicate an influence on the part of the poison on the general processes of nutrition in the body. A comparison of the symptoms as a whole in this way leads to a far more correct judgment, than if we take only one or two of the symptoms, which may easily lead to a com- parison with conditions which are absolutely dissimilar. For example, the observation of the mydriasis and of the spinal symptoms has led to a parallel being drawn between belladonna- and sausage-poisoning, not to mention other comparisons which are far more adventurous. An accurate study of the recorded cases and symptomatology of the sausage-poisoning will not allow us to draw any other than these somewhat negative con- clusions. The notion entertained by so many authors that the sympathetic nervous system is specially implicated rests on no more solid basis of facts than many other hypotheses about this condition. At least we fail to discover any symptom fairly attributable to the sympathetic. The implication of the sympa- thetic system of nerves is a relic of the time when all inexplica- ble pathological phenomena were set down to the sympathetic nerve, which was thus a sort of convenient scapegoat, because the functions of this nerve were not at all known at the time. We must beware lest we ourselves fall into a similar mistake by making abstractions from the known symptomatology of this disease. Husemann and Mueller rightly insist that sausage-poisoning has been frequently confounded with more or less widely differ- ent conditions which were due to other noxious things contained in articles of animal food. The most important of these is trichi- nosis, which appears several times to have given rise to a mis- taken diagnosis of botulismus. Nor should the illness arising from the meat of decomposing or diseased animals be identified with sausage-poisoning. It may, however, be combined with this and considerably modify its typical and usual symptoms. The conditions generated by putrefying substances are more akin to typhoid fevers—are perhaps actually a kind of typhus. In the remarks which follow we shall consider typical sausage-poi- soning only. SAUSAGE-POISONING. 539 The etiology, actual occurrence, and the extension of this form of poisoning by sausages are as peculiar as its pathology. An overwhelming proportion of the cases of poisoning have occurred in the kingdom of Wurtemberg and the adjacent Swabian parts of Baden. The Wurtemberg Black Forest and the neighborhood of the so-called Welzheimerwald are, according to Kerner and Paulus, the districts most commonly affected. Only a few cases occurred in the adjacent district of Bavaria. In all the rest of Europe, in spite of the general attention excited by the writings of Kerner, Schlosser, and other writers, only solitary cases of this poisoning are known. The following statistical account is taken from Kerner, Husemann, and the careful compilation of Mueller. In Kerner s first publication there were 76 cases (of which 37 were fatal), and some of these dated back to the year 1789. In his second publication (dated 1822), he adduced 155 cases (with 84 fatal ones). In 1827 there were 234 known (with 110 fatal), and in 1853, about 400 (with 150 fatal ones) had been pub- lished. Of late the frequency of cases of sausage-poisoning, even in Wurtemberg, seems to have considerably decreased. Whilst in the years 1832-1862, according to Faber,1 82 cases occurred in that country only, of which 19 ended in death, we could discover in the literature of 1866-1874 only 15 more, of which 12 belonged to Wurtemberg, 3 to Saxony (Dresden), and only one ended fatally. It does not seem likely that either less attention would be given to those cases, or that they would be less likely to be published of late years. Of the cases of sausage-poisoning occur- ring elsewhere than in Wurtemberg, the most recent is that of Niedner (Dresden).2 In Westphalia (Kreis Soest, Olpe) from 1820 to 1830 there were 18 cases ; in 1853, 1 case. In Lippe-Detmold, 14 cases in 1835 ; 1 in England in 1860 ; and 2 cases altogether in France.' In the larger towns, botulismus occurs extremely seldom ; nearly all the cases have been in country people, and in the earlier months of the year. It is not surprising that much care has been given to dili- gently seek the reason for this peculiar predisposition of the 1 Wiirtemb. Corr. Bl. 1854. 2 Berliner klin. Wochenschrift. 1866. . . 3_ See Mueller, loc. cit. 540 BOEHM. —POISONS. Swabian districts to sausage-poisoning; and no other explanation can be found than faulty methods of preparing the sausages. All other explanations have broken down, and need not be refuted here. Mueller mentions the following points in which the Swabian method of preparing sausages is favorable to the origination of the poison : 1. The meat used for the sausages is often insufficiently cooked. 2. A number of substances not suitable for sausages are employed in their manufacture, such as milk, flour, meal, brains, onions, and herbs like bennet-root (Nelkenwiirzel, Geum urba- num), too large pieces of fat, etc. 3. The proportion of liquids to solids in the sausages is a wrong one. The peculiar method of smoking or curing the sausages prac- tised in Swabia also has disadvantages of its own. The smoking places are generally very badly ventilated, and instead of the sausages being hung high up in the chimney, where the smoke is thin and cool, as in other places, they are hung immediately over the fire, in the hot smoke. Moreover, in Swabia, they do not, as elsewhere, keep up a gentle or small fire all night, so that in winter it is quite possible for the sausages to freeze at night and be thawed again in the daytime, and this condition is just the very thing to favor the decomposition of the sau- sages. And lastly, it is said that in Swabia it is common enough for people to add bullock's blood, or the blood of sheep, or even of goats, several days old, to the sausages—and the latter are not kept in proper, cool, airy rooms, but in wooden boxes or chests. Blood-puddings and liver-sausages most commonly give rise to the poisoning cases, but they have been known to occur after the use of beef-sausages, pork-sausages, and other kinds. One kind, known in Swabia under the name of " Blunzen," con- sisting of pigs' stomachs filled with sausage-meat, seem to favor the production of the poison by their great thickness, since it is easy to see that the perfect "smoking" or "curing" of so thick a mass can only take place slowly, and it is quite possible for the interior portions of the sausage to undergo a poison-generating process of putrefaction before they can be penetrated with the SAUSAGE-POISONING. 541 antiseptic constituents of the wood-smoke. All observers agree in considering the interior portions of the sausages as the most poisonous ; some say the only poisonous part is the inside, and there are even cases on record of poisoning, in which only those who ate the tainted inner parts became ill. All the authors on the subject agree in giving the following as the characteristics or outward signs which indicate that a sausage is poisonous: The putrefied sausages, or portions of sausage, when recently cut across, have a dirty, grayish-green color, and a soft cheesy- like, smeary consistence. They diffuse a very disagreeable smell of putrid cheese; the taste is disgusting, and sometimes causes smarting or soreness in the throat. Sausage-poisoning occurs rarely in solitary cases ; it generally attacks whole families which have simultaneously eaten the decomposing food. The intensity of the attack seems to depend both on the quantity of the poison ingested and on individual susceptibility to the poison. This susceptibility varies a good deal, and a careful consideration of the recorded cases does not permit of doubt on this point, though constitution, age, and sex all play their part. The asserted immunity of pregnant women has never been satisfactorily disproved by the occurrence of cases in such. Mueller thinks that the poison occurs in different sausages in different degrees of concentration (rather, perhaps, of potency). The course of botulismus is, as a rule, subacute, and very com- monly chronic. Cases running a very sudden course are rare. Under all sorts of circumstances poisoning by sausages is more tedious than most cases of poisoning by other well-known poi- sons. Even a fatal termination, as a rule, seldom closes the sick- ness in less than five or six days. The first symptoms of poisoning occur in the majority of cases in from eighteen to twenty-four hours after taking the injurious food. The extreme limits of the stage of latency are from one hour to nine days. Mueller has carefully collected 140 cases with reliable statements on this point. Accordingly, we find that a latent stage of less than twelve hours is just about as common as one of more than twenty-four hours. In 83 out of 542 BOEHM. —POISONS. the 124 cases the first symptoms occurred after twelve hours, and before the second day after taking the poison. We agree with Husemann in considering that the division of the symptoms of poisoning into stages is superfluous. Even Mueller's proposed division into a stage of invasion or excite- ment, and one of paresis or paralysis, cannot be maintained, since the gastro-intestinal symptoms do not invariably precede the nervous symptoms, but often enough both occur simulta- neously. As a rule, however, the sufferers complain at first of general discomfort and nausea, pain and sense of weight in the region of the stomach, quickly followed by diarrhoea and vomit- ing. Very often colicky pains, which disappear and then return again after a while, are the first symptoms, the severer symptoms not setting in till some days after. Sometimes also the scene commences with violent vomiting and retching, vertigo, cloudi- ness of vision, and difficulty in swallowing; lastly, the gastro- intestinal symptoms may be entirely absent, and the difficulty in swallowing, disordered vision, muscular weakness, and general prostration constitute the disease. Dyspnoea and feelings of suffocation (precordial anxiety) have been especially mentioned as being not infrequently some of the early symptoms. Although this condition is often protracted for several days with indefinite disorders, partly gastric and partly nervous, dur- ing which the patient very commonly goes about his usual business or occupations, in the majority of cases there is very soon so much weakness that they cannot long keep out of bed. The vomiting, often so troublesome at first, and sometimes, though rarely, persisting in the form of tormenting feelings of choking (Wiirgbewegungen) and retching, the diarrhoea and the colicky pains all recede into the background, and give place to the nervous symptoms. These are in part of a general nature, and in part limited to special regions and nervous tracts. Con- sciousness and thought, and all the special qualities of soul which are called the higher faculties, remain, with but few excep- tions, intact all through the whole course of the attack, although giddiness, headache, and an apathetic comatose condition in many cases indicate anomalies in the functions of the brain. SAUSAGE-POISONING. 543 Any definite paralysis of the voluntary muscles or of sensation has never been noted, any more than clonic or tonic spasms. It is rather extreme muscular weakness—which limits to the most minimal degree the exercise of the voluntary muscles, but never till just before death renders it impossible—than an actual paral- ysis. Any marked disorders of sensation are also absent, al- though the sensibility of the tips of the fingers is said to be diminished, and sometimes the patients complain of crawling and painful feelings in the extremities and back. Moreover, it is expressly declared that sleep generally occurs in a perfectly normal wa}^. The visual apparatus suffers in a very extraordinary way in sausage-poisoning. The first complaints of the patients point to diminished visual power, and are sometimes complained of as a cloud or mist before the eyes, sometimes as sparks, and some- times as mere weakness of sight. Very soon there is double vision, with diminished acuteness of vision; the powers of the ocular muscles are greatly limited, and sometimes quite abol- ished, and one of the most constant symptoms is paresis of the levator palpebrse superioris (ptosis). Very commonly also the nervus oculo-motorius is implicated, and the external rectus also paralyzed. The pupil is dilated, but does not become quite insensible to light; finally, the faculty of accommodation seems considerably lessened. Indeed, in some cases total blindness has been observed. Whilst, then, all the remaining nerves of sensation preserve their faculties unimpaired, some of the nervous apparatus sub- servient to respiration appears to undergo very extensive changes. This is indicated by the more or less perfect aphonia of those poisoned, with the varying degrees of general difficulty of breathing, and the frequently noted tormenting, and sometimes croupy cough, which, however, may very often really stand in close connection, as to their true cause, with the difficulty of swallowing (dysphagia), so that when nourishment is being given, whether food or drink, a portion may easily find its way into the air-passages. The disorders in the domain of the glosso-pharyngeal nerve are expressed in the almost pathognomonic symptom of dys- 544 BOEHM.—POISONS. phagia, which sometimes culminates in perfect aphagia or com- plete inabdity to swallow. The tongue also appears more or less hampered in its movements, and speech becomes stammer- ing and unintelligible. The remarkable dryness of the mouth and fauces indicates anomalies in the secretion of saliva. The mucous membrane of the mouth and pharynx shows either speckled or diffused red- ness, sometimes one, sometimes the other; sometimes there are also swelling, and aphthous formations; the tongue has a whi- tish coat. Lastly, the constipation which is constantly observed in the later stages, and the less constant retention of urine, must be considered as nervous symptoms, although little definite can be said as to their mode of origin. The hard scybala, sometimes broken down by energetic clysters, or discovered post-mortem in the large intestine, render it highly probable that the secretion of the various intestinal glands is considerably inhibited in sau- sage-poisoning. The signs of need of nourishment are often rather more mani- fest than is usually the case; some patients complain of hunger, the above-named difficulty of swallowing making it almost or entirely impossible to take nourishment. Thirst is mentioned only in a few cases. The organs of circulation appear greatly weakened in their functions. The pulse, which at first is feeble and slower than usual, vanishes sometimes altogether. Indeed, authors maintain that it is impossible in the later stages to make out the sounds of the heart. Accordingly we find the skin pale, and the mucous membranes of a livid color. The failing energy of the circula- tion is shown by the coldness of the skin—but no thermometric observations of the temperature are recorded. The rapid de- crease of the nutrient powers, the great emaciation, are the unavoidable result of the want of power to take food, and the disordered functions of the digestive organs. The organism, thus condemned to hunger, may, however, last a remarkably long time, unless the introduction of food into the air-passages, by causing oedema of the lungs, brings life to a more rapid end. As a rule, notwithstanding the long-continued depression of the circulation, there is not generally any oedema, with the exception of a few SAUSAGE-POISONING. 545 cases in which the formation of marasmic thromboses may give rise to it. Death generally follows without any specially violent symptoms ; it is preceded by a comatose or soporific condition, sometimes with slight general convulsions, from one day to three weeks after the poisoning. Those cases which end favorably are often marked by a very slow convalescence, in which the disorders of vision, and the diffi- culty of swallowing often persist for a long time, and the patients' strength returns to them very slowly and gradually. In some cases desquamation of the epidermis has been noted. We quote from Mueller the following statistics as to the mortality, and the time at which death occurs. Of 48 fatal cases, of which we have accurate accounts, 4 persons died a short time (!) after taking the poison. 2 persons in the first 24 hours. 6 persons accordingly on the 1st day. 2 a 2d " 4 « a 4th " 3 a 5th " 2 " " u 6th " 8 " " u 7th " 5 a 8th " 3 " a 9th " 8 u 10th " 2 a 13th " 1 a 14th " 1 person after three weeks. 3 " longer illness (?) 48 persons in all. From the figures given above (page 541), as the result of various collections, the general mortality appears to fluctuate between 23.2 and 54.2 per cent., and of late years the mortality is decidedly less than it was formerly. The tolerably copious materials which are now possessed by the pathologist in regard to alantiasis only allow of one safe VOL. XVII.—35 546 BOEHM. —POISONS. conclusion being drawn, which is, that this form of poisoning furnishes no post-mortem appearances diagnostic of it, and from the morbid anatomy alone, therefore, no conclusions can be drawn as to the real cause of death. Putrefaction occurs very slowly after death from sausage- poisoning. But Mueller's researches show that even this symp- tom is far from being a constant one, for out of 48 post-mortems carefully recorded, in 11, or nearly 25 per cent, of all, it is expressly mentioned that there was a very strikingly rapid development of putrescence. Post-mortem rigidity was just as often absent as present. The most common symptom was hyper- emia of the oesophagus, pharynx, stomach, and intestinal canal. The mouth was generally noted as very dry, and hard and dried- up faecal masses were found in the lower portions of the intes- tinal canal. The liver and brain in the majority of cases are described as (? abnormally) full of blood. The lungs also are generally gorged with black blood ; oedema and hepatization are only mentioned exceptionally. The bronchial mucous membrane often shows a dark and sometimes petechial reddening, and croupous membranes have once or twice been found in the trachea. When we consider how carefully and skeptically the records of congestion or fulness of blood in various organs are now scrutinized, and how little importance is attached even to the most accurate statements on these points, we must perforce consider these results as negative. The depressed state of the circulation renders accumulation of blood in the abdominal viscera extremely probable. As the sausage-poison manifests its power only slowly and tediously, the treatment of recent cases by the administration of energetic evacuants seems especially indicated. These must be chosen according to the particular case. Hitherto all other the- rapeutic rules and attempts in the later stages have proved utterly useless; and we need not, therefore, uselessly fill space with the details. Theoretically there can be no objection to the use of counterirritants in the later stages. But it must be re- marked here, that in the later stages of alantiasis the most dras- tic purgatives lose their power, and the only way in which the bowels have been sometimes relieved has been by the use of POISONOUS FISH. 547 clysters. In the convalescent stage, the treatment must be tonic and watchful. It is to be hoped that the more accurate knowl- edge of the dangers arising from improper methods of preparing sausages may gradually arouse the rural population from its apathy, and thus the occasion for this frightful form of poison- ing may cease. This hope is, in fact, justified by the great decrease in the number of cases of sausage-poisoning during the last decennial period. CHAPTER II. POISONING BY POISONOUS FISH. The question whether any species of fish is in existence, the use of which is capable, under all sorts of conditions, of setting up indubitable symptoms of poisoning in human beings—in other words, the question whether any fish is poisonous per se— though strongly contested, cannot be absolutely denied. All we can certainly say is, that no such fish is known at the present moment. On the other hand, the number of species of fish which are commonly regarded with suspicion as poisonous is very great. Nor can it be denied that, under special conditions, fish, which in themselves maybe perfectly harmless, may become poisonous. Only those cases of fish-poisoning which fall under this letter category can properly be included in a toxicological hand-book, for no other cases have been properly studied, or are sufficiently known. As regards fish suspected of being poison- ous, all that we could do would be to insert a long catalogue of, for the most part, very doubtful notices from travellers' descrip- tions, old books of natural history, and the like, of which little or no use could be made from either a practical or a scientific point of view—and we therefore forbear. Autenrieth,1 in a monogram on fish-poisoning, has cata- logued some seventy suspicious kinds of fish, with references and notices belonging thereto—and to this we must refer the reader ' Ueber das Gift der Fische. Tubingen. 1833. 548 BOEIIM.—POISONS. curious in such matters. There is also a catalogue in v. Hasselt- Henkei's' Toxicology, from which we extract only the general statement, that they are almost exclusively sea or salt-water fishes, and that of these the osseous fishes living in the tropical seas of the East and West Indies, are the ones which are most commonly regarded as poisonous. Amongst the Chinese and Japanese, the poisonous nature of some fishes, especially of the so-called sting-belly (Tetrodon ocellatus), is so generally and certainly believed, that those weary of life have even used them for suicidal purposes." The poisonous nature of certain fishes is indicated by the names which they have popularly received (Be- trayer, Purging-fish, Poison-fish, etc.). The more important clinical cases of fish-poisoning have all been traced to a few kinds of fish whose flesh is extensively used, particularly in the department of Volga in Russia. These fish are the various sturgeons (the great sturgeon or beluga, Accipenser huso, and the sterlet or Accipenser ruthenus, and Accipenser sturio or British sturgeon). Since these fish in them- selves are not the least poisonous, and serve thousands of people for their daily nourishment, we must accordingly, as in the case of sausage-poisoning, with which these cases show some anal- ogy, have to do simply with processes of decomposition (cata- lysis), which, being favored by careless methods of preparing the food, give occasion to the generation of poisonous substances. Scarcely anything worthy of note has been published regarding fish-poisoning, with the exception of these Russian cases. But then these singular cases occur with tolerable frequency, and the geographical domain of the fish-poison is far wider in extent than that of the sausage-poisoning. Accordingly, when Seng- busch, in' the two first years of the Medicinische Zeitung Muss- lands (1844-45), had drawn the attention of medical men through repeated notices to the then little-known circumstances, it was investigated at the instance of the Russian government, in 1857, by A. Owsjannikoff,3 and thoroughly discussed in the successive papers of Koch/ Berkowsky and Kieter.6 The practical results 1 Zweite Auflage. Braunschweig. 1862. a Autenrieth, loc. cit. p. 50. 3 Medic. Zeitschrift Russlands. 1857. 4 Ibid. 1858. 5 Ibid. 1858. POISONOUS FISH. 549 of all these investigations are little more satisfactory than in the case of sausage-poisoning, and may be briefly summed up as fol- lows : The two principal kinds of sturgeon (A. huso and A. sturio) are caught in part in the Volga and its tributaries by Russian fishermen, and in part in the sea, opposite the mouths of the Emba, by the so-called "free fishermen," and by them are sold as Persian or Emba fish in the Russian fish-markets (Watogen). As these fish are often of colossal dimensions, they are immedi- ately cut up and salted, and are then put into the fish-cellar (Wichodenl). The unsalted fishes, whether fresh or putrid, never set up the specific symptoms of fish-poisoning—and thus it is quite certain, as in the case of the sausage-poison, that common putrefaction is not the cause of the poison. Only the uncooked roe of the salted fish acts as a poison, and cooking perfectly deprives it of its poisonous properties. There is nothing particularly striking about the external appearance of this poisonous food. Amongst a large quantity of non-poisonous pieces lying in the same brine, there are, as a rule, only a few, and of these again only certain portions, which are poisonous, and these are only distinguished from the harm- less masses around by rather less consistence, lighter color, and a nasty taste and smell. These changes, it would appear, are now attributed to the defective salting, or salting of portions already putrid, of the inferior or Persian fish. Of the nature of the poison we know just as little as of the sausage-poison. Owsjannikoff has demonstrated that the salt-brine in which the poisonous fish has lain does not set up the specific symptoms. The outcome of all the various untenable hypotheses simply comes to this, that the fish-poison is probably due to a modified decomposition or putrescence, only developed in the salted fish, and as to whose nature, products, etc., etc., nothing certain is really known. Any trustworthy statistics as to the frequency of this poison- ing, the relative mortality, accurate geographical distribution, 1 Wooden boxes, sunk about two fathoms deep in the earth, in which the fish are preserved between layers of ice. 550 BOEHM. —POISONS. etc., such as those given of the sausage-poisoning, are rendered impossible by the vast extent of the Russian territory. Mean- while, fish-poisoning seems no way inferior to botulismus, and commonly enough ends fatally. The two sorts of poisoning can- not, however, be considered identical, when an accurate compari- son is made of the symptoms. However, they are so far similar, inasmuch as in fish-poisoning also the nervous phenomena are complicated with gastro-intestinal symptoms. The first symptoms do not occur before an hour, and not later than five hours after the use of the poisonous fish—they consist in oppression in the epigastrium, vertigo, darkening of the face, yellow and red vision (chromatopsy), and violent burn- ing, with a feeling of dryness, in the throat. The sick are periodically attacked with violent pains in the region of the stomach, which generally compel them to lie on the belly and to press the abdominal walls strongly inwards. In this way the abdomen appears to be retracted, and assumes the shape of a trough. The pains gradually extend to the rectum and the loins. As a rule, vomiting is absent. On the other hand, those poisoned suffer from great precordial anxiety, tedious dyspnoeal breathing, and very troublesome difficulty in swallowing, which, in the more intense cases, amounts to complete aphagia. Every attempt of the thirst-tormented patient to drink water excites the most severe cramps and a great amount of dyspnoea. The voice also becomes hoarse and toneless, and in the severer cases there is aphonia. The nervous symptoms, which begin with vertigo, disordered vision, etc., gradually increase to a more or less perfect paral- ysis of the voluntary muscles, whilst the higher faculties of the brain—consciousness, etc.—are retained to the last. The faculty of sight is totally lost towards the end of life ; the pupils are dilated and immovable. Ptosis is also named as a frequent symptom of this stage, at the end of which death occurs by stoppage of the breathing, whilst the heart continues to beat for some time after death. In the slighter cases, which are not fatal, most of the above named symptoms have been observed in less intensity, but they generally vanish in a few days, without leaving behind the POISONOUS CHEESE. 551 slightest disorder of the general health. One special form of fish- poisoning is ushered in with croupy symptoms, according to Berkowsky. The morbid anatomy of fish-poisoning presents absolutely nothing characteristic. As to the treatment, looking at the ex- treme obscurity which shrouds all the symptoms, it is manifest that it must be entirely directed to the relief of symptoms. CHAPTER III. POISONING BY POISONOUS CHEESE. Like other articles of food, cheese may become the vehicle of poisons of different kinds by their accidental or intentional ad- mixture with it. But we need not dwell on this. We have here only to deal with that form of cheese-poisoning which may be called specific, inasmuch as the poison is developed from the cheese itself. Although it is the article of animal food which is kept the longest, and although the preparation of it gives ample scope to putrefactive changes, yet cheese very seldom gives rise to severe disorders of health ; and, when compared with sausage-poisoning, the cases arising from cheese are very trifling, and, in most cases, scarcely deserve the name of poisoning. The numerous kinds of soft cheese, prepared in small families or on small farms, are generally the cause of the symptoms, while it is quite excep- tional to hear of symptoms arising from the use of cheese pre- pared in large quantities. As regards the nature of the cheese- poison, there is just as little really known as there is about sausage- or fish-poison. All that is known is, that it is usually very old and decomposing or decayed cheese the use of which by human beings has caused the symptoms of poisoning, whilst animals have partaken freely of it, and without any harm. The author knows of a case in which a dog ate a whole plateful at 552 BOEHM.—POISONS. once of a poisonous cream cheese which wras reserved for analy- sis, and not the slightest symptoms of poisoning were shown by the dog, though he was watched for many days. Many theories have been broached as to the composition and chemical nature of the cheese-poison, which need scarcely be discussed after what has been said about sausage and fatty poi- sons ; the more so, as most of them have been refuted, and have no practical value. It would appear that, by long keeping, albu- minous animal substances, such as sausages, smoked meat, salted fish, and cheese, undergo a species of putrefactive decom- position, the products of which are poisonous to human beings ; whilst ordinary decay or putrefaction does not generate any spe- cific poison, as has been shown by the fact that some people eat, without any harm, absolutely putrid and rotten-smelling soft cheese of various kinds. Cheese-poisoning occurs rather more frequently than else- where in the north part of Germany (Mecklenburg, Pomerania, Westphalia, etc.), but also in every other country, here and there, in solitary cases. In France—a country where there are, perhaps, more varieties of soft, fat (cream) cheeses than anywhere else—scarcely anything is known of cheese-poisoning. As re- gards the external marks of poisonous cheese, nothing definite can be said ; the more so as this kind of food is at best very re- pulsive in taste and smell to many persons ; but the taste of poisonous cheese has been said, in some cases, to be strikingly bitter and pungent. The effects consist of well-marked gastro-intestinal symptoms: colicky pains, vomiting, diarrhoea, and disgust at all sorts of food. Amongst nervous symptoms we have vertigo, anxiety, diplopia, headaches, great weariness, and muscular weakness. Amongst the earlier recorded cases several ended fatally, whilst in more recent times the effects have been less severe, and the cases have ended in recovery after some hours, or, at most, some days. Of twenty cases of cheese-poisoning observed in America two ended fatally, with severe pains and collapse.1 1 Husemann, Toxikologie. POISONOUS CHEESE. 553 Husemann also relates a case in which a mother and an infant at the breast both suffered from symptoms of cheese-poisoning, so that it would appear that the poison had passed into the woman's milk. The treatment of cheese-poisoning must be purely symp- tomatic. POISONING THE HEAVY METALS AND THEIR SALTS, INCLUDING ARSENIC AND PHOSPHORUS. NAUNYN. POISONS. General Treatises.* Taylor, On Poisons in Relation to Medical Jurisprudence and Medicine. Phila. 1848. —Christison, A Treatise on Poisons. 4th edition. Edinburgh, 1845.—Orfila, Traite de toxicologic 4. edit. Paris, IMS.—Husemann, Th. u. A., Handbuch der Toxikologie. Berlin, 1862; mit Supplementband. Berlin, 1867.—Schroff, Lehrbuch der Pharmakologie. Wien, 1873.—Van Hasselt, Handbuch der Gift- lehre ubersetzt von Henkel. Braunschweig, 1862.— Buchheim, Lehrbuch der Arzneimittellehre. Leipzig, 1859.—Oesterlen, Handbuch der Heilmittellehre. Tubingen, 1856.—Falck, Handbuch der speciellen Pathologie von Virchow. Bd. II. 1. Abtheil. Eiiangen, 1855.—C. G. Mitscherlich, Lehrbuch d. Arznei- mittellehre. 2. Aufl. Berlin, 1847.—Hermann, Lehrbuch der experimentellen Toxikologie. Berlin, 1874.—Pappenheim, Handbuch der Sanitatspolizei. 2. Aufl. Berlin, 1870. — Casper (Liman), Praktisches Handbuch der gerichtlichen Medicin. 5. Aufl. Berlin, 1871.—Kuehne, Lehrbuch der physiologischen Che- mie. Leipzig, 1868.—Ota?, Anleitung zur Ausmittelung der Gifte. Braun- schweig, 1856. CHAPTER I LEAD-POISONING. Manouvries, Gazette des hopit. 1874.—Kussmaul und Mayer, Archiv fiir klin. Medizin. Bd. IX.—Mehu, Bulletin general de Therapie. 1870.—Schoenbrod, Bayr. arztlich. Intelligenzblatt. 1873. — Westphal, Archiv f. Psychiatrie und Nervenkrankheiten. Bd. IV.—Erb, ibidem. Bd. \ .—Bernhardt, ibidem. Bd. IV. — Ollivier, Archives gener. de m^decine. 1865.—Hitzig, Studien iiber Blei- vergiftung. Berlin, 1868. I.—Heubel, Pathogenese und Symptome der chronis- chen Bleivergiftung.—Rosenstein, Archiv f. pathologische Anatomic 39.— * Only the indispensable works are mentioned. 558 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Gusserow, Ebenda. 21.—Hermann, Archiv f. Anatomie und Physiologic 1867. Brockmann, Die metallurgischen Krankheiten des Oberharzes— Tanquerel des Planches, Lead Diseases; a Treatise from the French, with Notes and Additions on the Use of Lead Pipe and its Substitutes. By S. L. Dana, M.D. London, 1848.—Lehwald, Untersuchung iiber die Ausscheidung von Arzneimitteln u. s. w. Breslau, 1861.—Melsens, Memoire sur l'emploi etc. Bruxelles, 1865.— Michel, Union medicale. 1867. Detection of the Compounds of Lead in the Animal Fluids and Tissues. Sulphuretted hydrogen will not separate lead from its com- pounds with the albuminous substances, with which it appears to be united in the body, nor from the secretions in cases of lead- poisoning. The tissue or fluid to be examined must always be ignited until all of the organic matter is completely destroyed, or better, since some of the volatile compounds of lead may be present, be treated with hydrochloric acid and potassic chlorate. From the filtrate, the lead can be obtained in the metallic form by observing the same rules as in inorganic analysis. Special care must be taken in every case to insure the purity of the reagents used in the investigation. Lead-poisoning is met with in two entirely different forms. a. Acute Lead-Poisoning, Every compound of lead which is easily soluble in the gastric juice can, when ingested in sufficient quantity, give rise to acute poisoning. In fact, however, severe or fatal cases of acute lead- poisoning are only caused by the acetate of lead, especially the normal acetate (sugar of lead). Formerly this was most fre- quently administered with criminal intent, but in recent times the cases are chiefly accidental. It is well established that acute poisoning of a mild grade may be caused by the use of badly glazed or old earthen or crockery ware, or of metallic vessels sol- dered with impure—containing lead—solder for the preparation or preservation of acid or fatty articles of food, on account of the formation of the acetate, lactate, or fatty salts of lead. Acute LEAD. 559 poisoning by lead has also been observed after the ingestion of articles of food colored with pigments containing lead, such as confectionery (white lead), lobsters (minium), and in children after sucking and licking playthings, visiting cards, envelopes, etc., which are covered with lead paints. The poisoning of in- fants by rubber nipples colored with white lead is worthy of note. The amount of sugar of lead which is necessary to produce severe or fatal lead-poisoning appears to be quite large :—from two to three drachms and upward. This renders it improbable that poisoning of the kind last spoken of can be anything more than a mild form of the acute. It has happened that much larger doses, an ounce and more, have been taken without fatal result. Formerly doses of from fifteen to thirty grains and more were not infrequently administered by physicians daily, during a considerable period. The symptoms in acute lead-poisoning depend upon the power to coagulate albumen, which the above-menticned lead compounds either possess in themselves, as sugar of lead, or acquire by the action of the gastric juice, as the oxide or carbon- ate of lead, which become converted in the stomach into the chloride ; these symptoms, in the mild, severe, or even fatal cases, are always those of corrosive gastritis ; the milder and less severe cases manifest themselves frequently by obstinate constipation. The matters vomited are not often of a dark (bloody) color. The presence of the dark line upon the gums, which will be treated of fully under chronic poisoning, does not appear to have been positively observed in the acute form of poisoning. The intensity of the poisoning (corrosion of the mucous mem- brane of the stomach) is, as in all similar cases of gastritis, largely dependent upon the fulness of the stomach. The progress of the disease is almost always very acute; death may take place in less than twenty-four hours ; in favor- able cases recovery is complete in from twenty-four hours to a few days. It is stated (Husemann) that symptoms of chronic poisoning may come on weeks and even months after recovery from the acute form. The diagnosis can only be made out with certainty by find- ing the acetate of lead (usually sugar of lead) in the food or the 560 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. excreta. In both of these the detection of the lead is possible without the previous destruction of the organic matter. The post-mortem appearances are those of acute gastro-en- teritis : the mucous membrane is covered with tough whitish coagula, as if it had been tanned, and the tissue beneath is red and softened. Treatment.—When no antidotes are at hand, give milk and the white of eggs. If there has been no vomiting, produce it by mechanical means and emetics. The best treatment is to empty the stomach by the use of the stomach-pump. The best antidotes are undoubtedly the alkaline sulphates- sulphates of sodium, potassium, and magnesium. When these cannot be at once obtained, phosphates, alum, or dilute sulphu- ric acid can be used. Vomiting and purging should always be produced, since the conversion of the lead compound into the sulphate may be imperfect, or the lead sulphate left behind in the body may give rise to chronic lead-poisoning. Otherwise the treatment is the same as for acute gastro-enteritis. b. Chronic Lead-Poisoning. Lead in any form, if introduced continuously for a long time into the system, acts as a poison. This is evident from the fact that even the least soluble compound, the sulphate, has this effect (Gusserow). Those preparations of lead which are soluble in the gastric juice, as the acetates, carbonate, and oxide, act most surely. All of these substances appear to act in the smallest possible doses, if introduced for a sufficiently long time. Louis Philippe's household in Claremont was poisoned after the lapse of seven months by drinking-water which contained not more than 0.0015 or even 0.0002 per cent, of lead. On the other hand, doses of from three to six grains have been given for some time, certainly for weeks, without any symptoms of poisoning having been produced. There are many ways in which these substances may be in- troduced into the body. Chronic lead-poisoning is frequently produced by moderate internal use of sugar of lead, and by the LEAD. 561 too energetic application of lead preparations in the form of cataplasms and plasters to the mucous membranes, wounds, or ulcers. Especially liable to lead-poisoning are workmen in white- lead factories (carbonate and oxide of lead), painters (white and red lead), weavers (lead weights on the looms), workers on gas- and water-pipes (lead cements), plumbers, printers (types), pot- ters (glazing of common pottery ware and tiles), lead-, tin-, and type-founders, workmen in file manufactories (striking files on lead cushions), workers in colored paper, sewers and makers of lace (the silk and lace being treated with lead compounds or weighted with lead), brush-makers (the bristles being colored by boiling with lead preparations), and workers in enamel, especially in glass enamel. Cases of chronic lead-poisoning have also been observed in actors and others who frequently use cosmetics containing lead, also as the result of cooking in badly glazed crockery ware (Schoenbrod), of drinking beer drawn through lead pipes, or of beer and wines from bottles (shot used in cleaning the bottles having been left); some cases have even been due to the use of snuff, which has been packed in spurious (lead-containing) tin- foil (the discovery of this method of poisoning has been wrongly attributed to M. Meyer'), and from sleeping on hair-mattresses (! Hitzig), the horse-hair having been dyed black by lead com- pounds, and poorly cleansed. One most remarkable case is that of a proof-reader, who was poisoned by reading printed proof for many years. Very rare are cases of poisoning, due to drinking-water con- taminated with lead by being drawn through lead pipe, although such cases have been observed. This rarity is explained by the fact, that almost all waters contain gypsum, which causes the formation of a coating of the insoluble sulphate of lead upon the inner surface of the pipe. The so-called soft waters, which con- tain but little mineral matter—such as rain and river waters, after having been kept for a long time in lead cisterns or wooden ones painted with lead paint or in badly tinned vessels—have frequently produced cases of severe lead-poisoning. 1 Compare Tanguerel des Planches, loc. cit. VOL. XVII.—36 562 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. With rare exceptions, severe cases of chronic lead-poisoning occur only in workers in lead, and the employments which most frequently give rise to it are those of painters, workers in white- lead factories, type-setters, lapidaries, and plumbers. As already mentioned, the quantity of lead taken in a single case has not so much effect in producing the disease as its con- tinued introduction; since it always happens, that even where very large amounts of lead compounds are ingested, only a very small quantity is absorbed into the blood, and it is almost imma- terial whether the compound used is one which is easily or but slightly soluble. This is shown to be very probable by the fact that, in all cases of chronic lead-poisoning, the blood and inter- nal organs contain but very small amounts of lead (0.02 per cent, in the maximum, Heubel); the elimination of the metal with the urine is certainly quite small, at least with urine which is free from albumen. In albuminous urine there appears to be a larger amount of lead. Yet LehwaldX view, that all of the heavy metals enter the urine in combination with albumen or with substances like leucin, etc., is incorrect, or at all events not proven. Lead is found in the bile and fseces (Heubel), but in too small an amount to account for the elimination of much of the metal from the body. In the blood and all of the organs lead is found only in com- bination with albumen, and there can be but little doubt that it is absorbed in this form. In cases of poisoning caused by remaining in a room, the air of which contains lead in a finely divided state, it is still unde- cided to what extent the absorption takes place from the mucous membrane of the air-passages. The possibility that the lead dust in the air can be applied to these passages is self-evident, but we still lack conclusive evidence that poisoning is caused in this way. There can only be a question about particles of lead suspended in the air as dust, since all of the preparations of lead are non-volatile ; in the light of this fact we must judge of those cases of chronic lead-poisoning which have been reported as having been caused, for example, by sleeping once in a freshly painted room. In all cases the conveyance of the lead into the stomach LEAD. 563 appears to play the most important part, whether the lead prepa- rations adhere to the hands, and are transferred from them to the food, or whether articles of food and drink are contaminated by lead dust which falls upon them. Also when lead dust in the air of rooms is the cause, the principal portion of the lead prepa- ration probably finds its way to the stomach by the swallowing of the particles, which adhere to the mucous membrane of the mouth. Still, it should be particularly remarked that lead dust in the air is of the greatest importance to the laborer. Bad ven- tilation of the work-rooms, the carrying of dust in the working- clothes to the living-rooms, or living and sleeping in the work- ing-rooms, favors the production of poisoning in great degree. Especially bad is the habit of eating food in the work-rooms, or of drinking water which has stood in the same ; also, according to all authorities, simple uncleanliness, unwashed hands before eating, and the habit, which many workmen have, of holding be- tween their teeth or lips the paint-brush, types, or other article. All those influences which affect the nutrition of the in- dividual remain to be considered, such especially as the use of alcoholic drinks, which increases largely the disposition to be affected by lead. There is no doubt, however, that, apart from the variety of manifestations in single cases, one person is more easily affected by poison than another. This is shown by the fact that in some persons the first symptoms of lead-poisoning are very often followed by others, in spite of all care; but there are others who have been exposed for ten years at a time to the greatest danger of chronic lead-poisoning without showing any severe symptoms. The greater susceptibility of women, mentioned by Tanquerel, is not proven, but children appear to be more susceptible than adults. The summer months show a greater frequency of cases (Tanquerel), due probably to external influences. The time within which symptoms appear after exposure cannot be esti- mated ; poisoning has frequently been observed within a few weeks after the therapeutic administration of considerable doses of lead compounds (see above); in other cases years elapse before the symptoms manifest themselves with certainty. 564 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. In some cases there is no exposure to the poison at the time when the symptoms (colic, etc.) appear. Thus one case is noticed in which the symptoms of chronic poisoning appeared fourteen months after an attack of acute poisoning caused by sugar of lead solution, and another in which they appeared fourteen days after the discontinuance of the therapeutic use of lead com- pounds (Sandras, Pereira, van Hasselt). It is proved beyond doubt that symptoms of lead-poisoning can appear in people who have once been affected, years after all exposure to its action has ceased. Thus, one case is recorded by Tanquerel des Planches (No. 14 Marechal) of a painter who, annually for nine consecutive years after leaving his business, and ceasing entirely to handle lead preparations, had attacks of well-characterized lead colic and other lead troubles. Lead-poisoning has been observed in animals—horses, cats, dogs, and others—brought on not only experimentally, but also by living in an atmosphere charged with lead dust, drinking water containing lead, etc., colic and encephalopathy being the symptoms produced. Nothing has been established in reference to the dependence of the manner in which the affection manifests itself upon the form of preparation used, or upon any special mode of applica- tion. Recently Manouvriez has stated that, in the case of lead paralysis at least, a local influence could be shown. Yet his cases are not conclusive, and many other observers do not agree with him. In many cases, doubtless, the influence of other poi- sons, as copper, arsenic, etc., is brought to bear. History. Chronic lead-poisoning has been recognized for a very long time. We find it hinted at unquestionably in works of the old Greek authors. Arabian physicians (Avicenna) have given minute descriptions of lead colic. It also appears that the arthralgia and paralysis were known in the early ages. The most important writers of recent times are Stockhausen (1656), and Tanquerel des Planches (1830). The works of the latter stiH remain the standard and guide in this subject. LEAD. 565 General Description of Chronic Lead-Poisoning. Persons affected with chronic lead-poisoning show, sooner or later, almost without exception, signs of impaired nutrition. Even when the patient himself experiences no diminution of his strength and general health, his aspect becomes changed, and the skin assumes a peculiar yellowish hue. This color of the skin Tanquerel designates by the name of icterus saturninus ; Tanquerel does not, however, use the word icterus in the sense in which it is used to-day, but states that this color has nothing whatever to do with the biliary pigments. There is rarely want- ing, as a characteristic mark of the action of lead, a dark or bluish-black line at the junction of the teeth and gums, always most strongly marked upon the upper jaw. This line shows most plainly in people who have bad teeth, with deposits of tartar upon them; care should be taken not to confound with this the livid color of the gums at their junction with the teeth, which is frequently seen in such people. The black edge of this line is due to the deposition of particles of the sulphide of lead in the substance of the gum, as Tanquerel has shown ; this is probably caused by the action of sulphuretted hydrogen, which is easily formed by the decomposition of food remaining upon the edge of the gum, especially if the teeth are not properly cared for, upon the particles of lead mechanically adhering to the mouth. In very rare cases this slate color spreads over the entire gum, or even over the whole mucous membrane of the mouth (Tanquerel). The patients themselves notice, as further signs of the action of lead upon the system, a characteristic, insipid, sweetish, mildly astringent (lead) taste, at the same time a very fetid breath, and occasionally a marked slowing of the pulse (to 40 per minute, Tanquerel). Emaciation rarely fails to appear in cases where the action of lead has lasted for years or even longer. This emaciation is more noticeable in the muscular tissue than in the panniculus adiposus. Often the progress of the disease stops here, even though the person remains subject to the action of the lead to a 666 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. greater or less degree for years continuously. In other cases symptoms of specific lead disease appear. These may be divided into four principal forms, viz.: 1. The colic. 2. The arthralgia. 3. The paralysis. 4. The encephalopathia saturnina with amaurosis saturnina. Colic is the most frequent of these symptoms, and encephalo- pathy the least; the statistics of Tanquerel give as their relative frequency: Colic............................ 1217 Arthralgia...................... 755 Paralysis....................... 107 Encephalopathy................. 72 As a rule, colic is the first symptom by which chronic lead- poisoning manifests itself, yet sometimes one of the other symp- toms appears first; in the later progress of the disease these symptoms can interchange in the freest manner ; or the same one continually recurs—colic the most frequently ; much more rarely, the disease always shows itself in the same person by one of the less common symptoms, paralysis or encephalopathy. The duration of the intervals between the attacks vary very much, from days to weeks or even years. It is often noticed, that when an attack of colic or arthralgia comes on, with paraly- sis already existing, this latter symptom becomes aggravated. Mixed forms, or the simultaneous appearance of two lead affec- tions, are not rare. As a rule, an attack rarely results fatally ; at least death is almost exclusively the result of saturnine ence- phalopathy, but with this symptom it is quite common. When there has once been a pronounced attack of lead dis ease, the danger of a relapse is very great, unless the cause of the poisoning can be removed. The lead dyscrasia progresses with frequent repetitions of the attacks in many cases, but in some without their further appearance; an obstinate dyspepsia is developed, and following this a more and more cachectic condi tion of the patient; the peculiar yellowish color gradually gives way to an anaemic one, and temporary oedema, weakness of LEAD. 567 locomotion, apathy, and moroseness show themselves, as in all similar diseases. In the highest degree of cachexia there is oc- casionally a well-marked tremor, never, however, to the same extent as in mercurial poisoning. In this cachectic condition the patient vegetates for years, or even tens of years, and dies sooner or later ; death is usually caused by some complication. The most important complications are: phthisis, pneumonia, pleurisy, and especially nephritis—the last is relatively very fre- quent ; gout is also not rare in lead disease.2 Tendency to con- stipation exists almost during the entire course of the disease; usually this is only severe on the appearance of the paroxysms, especially at the commencement of an attack of colic. Anatomical Characteristics. No characteristic anatomical change in chronic lead-poisoning is known, except the degeneration and atrophy of the paralyzed muscular tissue in cases of lead paralysis. Atheromatous de- generation of the arteries has been frequently observed. Other changes which are observed after death are due to complications and not to the lead disease proper. Only a negative result has been obtained by an examination of the bodies of those who have died with lead encephalopathy. At least, the examina- tions of Tanquerel, who found an enlargement of the sympa- thetic ganglia of the neck, of Brockmann, who found induration of the same, and of Kussmaul and Meyer, who found hypertro- phy and sclerosis of the connective tissue in the coeliac ganglion, are of no value at present. General Prognosis of Chronic LeactPoisoning. The prognosis in reference to the special forms in which the disease manifests itself will be spoken of in connection with each. The prognosis is especially affected by the nutrition and manner of living of the individual, and account must also be 1 Vide Lancereaux, Gazette Medicale de Paris, 1871. Garrod, Nature and Treat- ment of Gout. London. 1865. etc. 568 NAUNYN. —POISONING BY THE HEAVY METALS, ETC. taken of the peculiar susceptibility in each case. We may as- sume that the sooner positive symptoms of the disease appear after the commencement of exposure to the action of lead, the greater is the susceptibility; hence the danger is greater in the case of young persons, if they cannot avoid exposure to lead. In all cases in which the symptoms have already appeared, the prognosis is bad, unless the patients can be completely re- moved from the influence of the poison. The prognosis depends somewhat also upon the form of the attack: encephalopathy and paralysis, or even arthralgia, indicate generally a more se- vere seizure. In severe cases, the attacks are repeated, but seldom in the milder cases; and death, or complete invalidism resulting from the lead cachexia, is the unavoidable result. The prognosis is much better in those cases where the marked symptoms of lead- poisoning are wanting; in such cases the cachexia generally makes much slower progress, and it not seldom happens that the apparently severe digestive disturbances due to lead remain sta- tionary for many years, the patient being able to work during the whole time. In those cases in which the patient can be removed from the influence of the poison, a complete cure may be expected; yet attacks of the colic, etc., are occasionally met with weeks, months, and even years after the removal of the patient from the influence of lead. The degree of the cachexia in such cases is important in enabling us to judge of them ; if it is very marked, the prognosis must be a guarded one. Treatment of Lead-Poisoning in General. Rapid elimination of the poiscm and the prevention of its further absorption only will be dealt with. A discussion of the means of treating individual symptoms, or of counteracting the existing anaemia, would be out of place here. To facilitate the elimination of the metal, the administration of potassium iodide is to be recommended, as well as in the case of mercury (Melsens et ah). The action of this remedy is so great that, according to Michel, its habitual ingestion by those LEAD. 569 exposed to the action of lead is a sure prophylactic against poi- soning. In addition to this, recourse should be had to means which hasten tissue metamorphosis. In this way may be ex- plained the peculiarly favorable effects of warm baths in cases of chronic poisoning by lead and other metals. More important is the prophylactic treatment—the diminu- tion or prevention of the introduction of lead. This is easily accomplished in cases of accidental or criminal poisoning, when it is only necessary to ascertain the nature of the disease and source of the poison, in order to stop its absorption at once. It is much more difficult where the poisoning is the consequence of a certain occupation. First, it should be regarded as settled, that there is no certain antidote. The reputed efficacy of sulphuric acid lemonade has no foundation ; this Tanquerel knew long since, and there can be no longer any doubt of its entire inefficacy, since we know that the sulphate of lead shares the poisonous properties of the other lead compounds. Still less to be relied upon are drinks containing nitric acid and sulphuretted hydrogen. Sponges, respirators, masks, and other complicated arrange ments to protect the workmen from inhaling the dust, do not succeed, since they prove too great a hindrance to them in their work. The only effective means are hygienic. First, care should be taken to have the work-rooms sufficiently ventilated; the most dangerous parts of the work should, if possible, be done in the open air. Next in importance is absolute cleanliness on the part of the workmen. A point of great importance, and often men- tioned, is to forbid them, under penalty, eating or drinking in the workshop, and not to allow them to leave the room without care- fully washing their hands. It should further be absolutely insisted upon, that they change their clothing, at least their outer garments, before leaving their work. Opportunity should be given them in or near the factory to frequently take warm baths. Menu recommends, for the purpose of thoroughly re- moving from the skin any particles of lead which adhere to it, that the water of the bath should contain sodium hypochlor- ite, which he prepares by mixing in two and a half gallons 570 NAUNYN.—POISONING BY THE HEAVY METALS, ]<:TC. of water thirteen ounces of chlorinated lime with sodium car- bonate. A not unimportant point, which Tanquerel has already men- tioned, is that in factories in which lead compounds are used, the different parts of the work are dangerous in different degrees. Hence no one person should be employed on the same kind of labor, especially the more dangerous ones, continuously. And immediately upon the appearance of the slightest symptom of lead-poisoning, the workmen should be, for a time, removed from the more dangerous work. In an otherwise badly managed white-lead manufactory in Switzerland, in which the Dutch method is used, there has been no case of severe lead disease for many years, on account of the observance of the last two pre- cautions. Lead Colic (Colica Saturnina). As already mentioned, this is the first, and by far the most frequent, form in which chronic lead-poisoning manifests itself. Not unfrequently it comes on very suddenly, without any pre- vious symptom ; in most cases, however, some warning is given. For weeks preceding the attack of colic, the patient is tormented by moderate wandering pains, which are sometimes more severe immediately after eating, and sometimes are entirely indepen- dent of meals. At the same time increased disturbance of diges- tion is noticed, loss of appetite, increase of the peculiar sweetish taste, which perhaps already exists as a sign of lead-poisoning, increase of constipation, and in some cases diarrhoea. With these prodroma the case can be arrested, if the proper treatment is resorted to immediately ; in most cases these symptoms are fol- lowed by the outbreak of the disease, beginning with colicky pains. These vary in intensity ; they may be inconsiderable, or may, on the other hand, be so severe that the patient attempts suicide. According to the severity of the attack, the patient is affected mentally in a greater or less degree, often being excited to the utmost violence. Besides the attacks of colic, which rarely last more than a few minutes (Tanquerel saw them last for hours), there are some sensations of pain which do not entirely LEAD. 571 cease, a continued griping and cramp in the abdomen being pres- ent almost without exception. Pressure on the abdomen never increases the pain in severe attacks, but, on the contrary, almost always gives relief; at the time of the remission it is agreeable to the patient, and very rarely increases the pain. The seat of the pain varies; generally it is in the region of the umbilicus, sometimes in the upper and sometimes in the lower part of the abdomen, and rarely in the region of the kidneys ; no classification of- lead colic based upon this is of any value. In many cases the pains are accompanied by tormenting and frequent tenesmus; in others, together with or in place of tenes- mus, there is strangury or retention of urine, with severe pain extending along the course of the ureters or spermatic cord to the kidneys, or to the penis. There are also shooting pains in the breasts. These pains are doubtless in part due to powerful contraction of the intestinal wall; at all events, Tanquerel suc- ceeded in feeling very energetic contraction of the rectum, during an attack of colic, by digital examination ; he also thought that he could detect a contraction of the sphincter vesicae by the introduction of a catheter. In addition to the colic, retraction of the abdomen and con- stipation are rarely wanting. The retraction of the abdomen is often very great—so great that the bodies of the vertebrae can be seen through the skin of the abdomen. The entire abdomen is generally sunken, so as to be boat-shaped, and is hard; at times the retraction is irregular. In not a few cases, however, this is entirely wanting, and in its place there is swell- ing of the abdomen. The same is true of constipation; not- withstanding the importance of this symptom in the diagnosis of lead colic, yet it is in many, and even severe cases, wanting, and diarrhoea occurs in its place. Nevertheless, in by far the majority of cases constipation is coincident with the pain, not only in time but also in degree, and they may last for several weeks. Violent vomiting, or at least nausea, is also a very com- mon occurrence. The vomiting is often preceded for a long time by ineffectual retching, and occurs generally during the 572 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. remission of the colicky pains. The vomited matters are usually tinged with bile. In addition to the symptoms which have been already men- tioned, others which appear to be constant, or at least frequent, are the peculiar pulse and the icterus. The latter, in most cases, occurs only in a mild degree—recognized by the yellow color of the sclerotic and feeble reaction to the tests for bile pigments- - and is without importance ; it is very rarely intense. The peculiar pulse is certainly one of the characteristic symp- toms of lead colic. It is always diminished in frequency and often to a considerable extent—to 30 beats per minute (Eulen- berg) ; it is usually full and very hard. Its condition is con- sidered of special value in connection with the theory of lead- poisoning. According to Tanquerel, the pulse is frequently irregular, i. e., variable in frequency, but not intermittent. Respiration is, especially during the attacks, somewhat in- creased in frequency without any existing disease of the lungs. Fever rarely exists, and the increase of temperature is always inconsiderable. The appetite is always much diminished, and the urine is usually concentrated; in regard to its quantity we have no cer- tain data ; it frequently contains a small amount of albumen. The intellect is always intact except during very severe attacks of colic. Tfte course of the disease, chiefly limited to the colic, is very varying. As a rule, it is more severe in the evening and night, when all of the symptoms become worse. Even after long inter- vals free from pain, and when the disease seems to be at an end, relapses are very frequent; they occur after the expiration of days and weeks. The duration of the disease is, as a rule, not more than a week, especially in recent cases, but it can be pro- longed very much by repeated relapses, and may finally, espe- cially in old cases and where there is a fresh exposure to the action of the poison, become chronic. The termination of the disease following the cessation of the colic is of ten very sudden ; then all of the other symptoms cease- retraction of the abdomen, constipation, vomiting, diminution of the pulse—and complete recovery is often surprisingly rapid. LEAD. 573 The complications consist of the other forms of lead-poisoning, and in addition to these, some observers have noticed violent attacks of enteritis. The prognosis is on the whole very favorable ; death in cases of lead colic is caused by the supervention of encephalopathy, rarely by lead paralysis or any accidental complication. Accords ing to Tanquerel's extensive statistics, the mortality is two per cent. Post-mortem examination in cases of death during lead colic reveals nothing important. With the exception of the more or less limited or widespread contraction of the intestinal canal, and hypertrophy or atrophy of the intestinal wall, the autopsy gives a negative result. The appearances reported by Kussmaul and Meyer, mentioned above, were found in one case, in which the patient died after a single attack of colic with symptoms of severe enteritis. The treatment of lead colic has always been regulated by the most varied theoretical views. Attempts have been made to ren- der the poisonous metal innocuous by sulphuretted hydrogen and ammonium sulphide, and by baths of the alkaline sulphides ; the supposed inflammation was counteracted by antiphlogistic measures, etc. Here also we must refer to the classical work of Tanquerel, who was deeply interested in the history of this sub- ject. In this disease, where there is no clear insight into the manner of progression, and where empiricism has not been able to establish a specific remedy, a rational treatment can only be directed to the symptoms, and the main object is to counteract the colicky pains by means of warm baths, hot fomentations on the abdomen, and narcotics internally and subcutaneously. Of the narcotics, opium has for a long time been preferred in this disease. Morphia undoubtedly answers the same purpose, and chloral taken internally has the most excellent effect, as in all spasmodic conditions of the muscles of the alimentary canal. Cathartics have been found by experience to be of great value, and we are not justified in ignoring them by the theoretical con- sideration that the primary spasm of the intestine is the cause of the suffering. As a rule, mild cathartics, such as senna, mag- nesium sulphate, and castor oil, together with narcotics, are 574 NAUNYN.—POISONING BY THE HEAVY METALc, ETC. sufficient; in severe cases purgatives should be used—even cro- ton oil, as recommended by Tanquerel, one drop daily in thick barley-water. Violent vomiting may be treated with ice pills, and narcotics given subcutaneously, if necessary ; the other remedies required, especially the cathartics, should be given, under these circumstances, as enemata. Any existing icterus, albuminuria, etc., require no special treatment. Too much must not be expected from drugs given to hasten the elimination of the lead from the system, for reasons which will be discussed later when speaking of theoretical points. Most can be accomplished in this respect by the use of warm baths and cathartics, and the use of potassium iodide is occasionally indicated. Arthralgia Satarnina. This is, according to Tanquerel, the second in frequency of the forms in which chronic lead-poisoning manifests itself. In its course there are many points of similarity with lead colic. After prodroma' similar or analogous to those of colic, or even without prodroma, there appear, more or less suddenly, tear- ing and burning pains, located in the region of the joints or of the muscles over them. These pains exhibit violent exacerba- tions and remissions until they completely disappear. They are not of a true neuralgic nature, since they do not follow the course of the nerves. The existence also of the characteristic pressure points,' as in the so-called joint neuroses(Esmarch),is not clearly established. The exacerbations are accompanied by cramps, i. e., tonic contractions of the muscles involved, which are very pain- ful to the patient. These cramps are demonstrable by the hard- ening of the involved muscles and consequent position of the limb. The attacks are brought on by exercise and by cold. The pains are diminished by pressure; inflammatory appearances, such as swelling, etc., over the joints, ligaments, and tendons, are entirely wanting. These pains occur by far most frequently in the lower ex- : See Vol. XL of this Cyclopaedia, p. 291. LEAD. 575 tremities, especially over the knee, much less often in the upper extremities (elbow, shoulder). The muscles most frequently attacked in the extremities are the flexors (Tanquerel): in the leg, those muscles which form the calf of the leg ; in the thigh, the flexors of the leg ; and then the flexors of the thigh in the bend of the hip. The same is true of the upper extremities; in the body, often the long dorsal muscles are affected, especially those in the region of the loins; in the thorax, all the muscles may be affected, and the resulting affection may, in severe cases, very closely resemble angina pectoris (Tanquerel). Occasionally the muscles of the neck are involved. The smaller joints and the muscles about them are rarely affected. A tremor of the affected muscles is often noticed. The sever- ity of the pain is often very great, and under such circumstances its reaction upon the general condition of the patient is felt. Otherwise this symptom shows less irregularity than lead colic. Constipation and the peculiar character of the pulse are absent. There is also no fever. Its course, as already mentioned, is not unlike that of lead colic. The pain suddenly ceases after many variations and re- missions, and with the cessation of the pain the whole affection disappears, but there is the same tendency to relapse. No com- plications need be mentioned, except the frequent occurrence of this disease after, simultaneously with, or preceding attacks of lead colic and other lead affections. Tlie prognosis is, on the whole, more favorable than in lead colic, especially in regard to mortality. Treatment.—Warm baths doubtless have the greatest effect. That sulphur baths are alone sufficient (as Tanquerel asserts) would be doubted at the present time; the number of cases upon which Tanquerel bases this statement is not sufficient. In addi- tion to warm baths, galvanization locally and of the sympathetic should be tried. The use of purgatives is not to be recommended ; potassium iodide should be tried, since it seems to act favorably in all rheu- matic affections (muscular rheumatism, etc.). 576 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Lead Paralysis. This is the third of the lead affections, both in frequency and in order of succession. It is observed generally after the colic or the arthralgia, or after both, but may, like all of the forms of lead disease, occur without having been preceded by any of the others. Tanquerel's compilation is interesting, showing as it does that paralysis may occur as early as on the third day after the first exposure to lead ; further, that in 102 cases, 9 occurred in the course of the first month, and 14 in the course of the first two months; that 34 developed in the course of the first two years, though often this symptom did not appear until much later—thus 48 cases occurred after ten years, and some even after fourteen and twenty years. Even after fifty-two years of exposure to lead without any serious detriment lead paralysis has been observed. In its localization lead paralysis shows an almost freakish opposition to arthralgia, which is seemingly so nearly related to it. In the latter a predilection is manifested for the lower ex- tremities and for the flexors, while in paralysis, in the great majority or cases, at first at least, the upper extremities and the extensors are attacked. Paralysis of the extensors of the hand and fingers (especially of the extensor communis), with freedom of the supinator, is the characteristic and well-known form of lead paralysis ; next, the triceps and deltoid are most frequently attacked. The same is true of the lower extremities when they are attacked, which rarely takes place until long after the paral- ysis of the hand and fingers, the extensors (dorsal flexors) of the foot, on the peroneal side, and those of the toes losing their power. Only in rare cases are the respiratory (intercostal, Tan- querel) or the laryngeal muscles affected. Rare, however, as cases of this form of paralysis, consequent upon lead-intoxica- tion, are, still its relationship to the large group of lead diseases is positively established by the frequent appearance of paralysis of these muscles in animals poisoned with lead. Horses in lead- mills frequently have paralysis of the vocal cords, rendering tracheotomy necessary. Even Tanquerel has never observed LEAD. 577 paralysis of the muscles of the face or eye in lead disease. It is to be especially observed that the extent of the paralysis, as in the forearm, does not correspond with the distribution of a peri- pheral nerve.1 The muscles affected in ordinary lead paralysis of the hand and fingers are, as a rule, those which are supplied by the radial nerve, but usually one or more of the muscles receiving fibres from this nerve remain unaffected. In the majority of cases the paralysis affects the extremities of both sides, and often the same muscles in both extremities. There are cases, however, in which only one extremity is affected, and cases are not very rare in which the muscles paralyzed in the two extremities are different. In rare cases lead paralysis may resemble hemiplegia, on account of both the upper and lower extremity on the same side being attacked. The characteristic appearance of lead paralysis is often ob- scured by the fact that it may be exceedingly limited—confined to the extensor of a single finger, for example—or by the fact that beginning in the usual manner, it may involve all of the muscles of a limb, or may even finally spread over the whole body. Very slight impairment of the function of the flexors is observable at an early stage, even when the paralysis seems to be purely of the extensors. Tanquerel, and after him others, explain this by the defective extensibility of the paralyzed muscles. Better is the explanation, that in pure extensor paralysis the position of the hands, for example, is unfavorable to the exercise of the flexors, and limits their function. Sensibility is usually unaf- fected in lead paralysis ; more frequently there are at the com- mencement pains in the affected muscles or corresponding bones, and often in other muscles ; rarely there is slight and very rarely complete anaesthesia of the skin, corresponding, or nearly corre- sponding, to the distribution of the paralysis; in individual cases there is anaesthesia of the deeper parts also. On the other hand, trophic disturbances are never absent. The extraordinarily rapid atrophy of the paralyzed muscles, often reaching a high degree in a few weeks, is, next to the localization, the most characteris- 1 Vide Ernst Remak, Zur Pathogenese der Bleilahmung. Inaug.-Dissert. Berlin. 1875. VOL. XVII.— 37 578 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. tic sign of lead paralysis. The shrinkage of the muscles attains a degree seldom seen, except in progressive muscular atrophy, and it is so much the more apparent in this disease, since the neighboring muscles preserve their normal and well-developed volume ; thus the atrophy of the extensors produces a deep furrow on the outside of the forearm. By examination with electricity there appear early those signs which are seldom wanting in peripheral neuro-paralysis : speedy diminution even to complete disappearance of the reaction to the faradic (inter- rupted, induced) current; unchanged, temporarily increased reac- tion to the galvanic (constant) current; occasional appearance of greatly increased excitability to mechanical irritants ; predomi- nance of KaSZ,' and increase of the time occupied by the contrac- tion wave. The observation of Erb, who found this abnormal reaction very well marked in a patient with lead paralysis in mnscles in which the paralysis had not become developed, is very interesting and important. In the further course of the paralysis many deformities may arise, such as dislocation in the more movable joints, as the shoulder and phalanges, and the tumors thus formed—upon the back of the hand, for example— can very easily be mistaken for gouty swellings ; as mentioned above, however, true gouty swellings occur as a complication. Often there is tremor of the paralyzed muscles (Tanquerel), especially at the time of the appearance and disappearance of the paralysis. Tremor is also frequently observed in the facial muscles, which are never affected with lead paralysis. The onset of the paralysis usually follows certain prodroma, such as sensations of pain and dulness in the affected limbs; it comes on quite gradually, though sometimes suddenly, after an attack of colic or encephalopathy, and simultaneously with or soon after the cessation of these. In rare cases it comes on suddenly and without any prodroma. Once started, it may ex- tend gradually and irresistibly. The progress of the paralysis is very varied. It may disap- pear spontaneously, or under treatment, in a few days or weeks ; or it may become stationary at any stage and last for years. 1 See Vol. XI. of this Cyclopsedia, p. 273. LEAD. 579 iii cases where it remains, it becomes worse with the onset of any new form of lead disease. Convalescence, almost without excep- tion, is gradual, yet, considering the extent of the paralysis and atrophy, comparatively rapid, the atrophied muscles being re- placed by new tissue. Relapses in the same muscles are not rare. The prognosis depends upon the length of time during which the paralysis has lasted, and upon the extent of the atrophy; the greater these, the more unfavorable is the prognosis; the more extensive the paralysis, the worse the prognosis ; it is more unfavorable in the relapse than in the first attack ; it is doubtful, where there is only considerable atrophy, and it is not absolutely bad where the atrophy is not complete. Tanquerel observed a fatal result follow, in two cases of paralysis of the intercostal muscles, by asphyxia. In addition, we would mention progressive muscular atrophy as having been frequently observed in patients suffering with lead disease. The pathological changes are found in the muscles and per- ipheral nerves. Examination of the central nervous system has always given negative results. The most important change is that observed by Westphal, who found in one case of lead paral- ysis, which developed gradually during two years, an abundant new formation of nerve-fibres in the radial nerve, which lie rightly considered to be due to previous degeneration ; this was confirmed by an earlier observation of Lancereaux. Several authors, and among them Bernhardt, found, in ex- amining muscles atrophied by lead paralysis, that they were shrunken and very granular, and between the fibres he observed an abundant formation of connective tissue poor in nuclei—in part probably the empty sheaths of fibres, the contents of which had disappeared. Treatment.—Besides the means employed in lead disease generally—tonics, warm baths, potassium iodide—electricity in its different forms, such as local faradization and galvaniza- tion, is the special treatment for lead paralysis, and very bene- ficial results are doubtless obtained by it. The use of strychnia in this disease, as in others, has been nearly forgotten. The powerful effect which this substance has been shown to have 580 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. upon the excitability of the nervous system, and the wonderful results which have been obtained by its use in other fields, should warrant its more extensive employment in this also. The statement which Tanquerel makes concerning the action of this drug in lead-poisoning is of great interest, and his assertion that it gives good results is quite credible. Tanquerel gave this drug internally and by the endermic method in slightly toxic doses ; in most cases he gave it until slight tetanic spasms were produced. The enormous doses which he speaks of—up to nearly two grains, usually from one-sixth to one-half grain— were probably borne, as he himself thought, owing to impurity of the preparation used. The use of this drug is indicated in lead-poisoning where the patient for any reason cannot bear the application of electricity, or where the latter does not soon give visible results. It may be given by the mouth, or, if feasible, locally by subcutaneous injection. It should be remembered that relatively large doses are required to produce good effects, and also that the susceptibility of different individuals to the action of the drug varies greatly; that occasionally this drug appears to have a cumulative action; and further, it should be remembered, when about to increase the dose, that therapeutic and very toxic doses lie very closely together. Brief mention must here be made of the anaesthesia, not* including amaurosis, which will be treated of later under the head of encephalopathy. Anaesthesia, properly speaking, is rare in lead-poisoning; Tanquerel observed it in eleven cases. Usually there is anaesthe- sia of the skin only, rarely of the skin and deeper tissues. It has no definite relation to the muscular paralysis; it may appear with paralysis and also with colic and arthralgia. There may be both arthralgia and anaesthesia of the skin in the same locality. On the whole, in localization and in its course it is very vary- ing and, as it were, freakish. The attack in one place disappears to-day only to appear in another in a few days ; according to Tanquerel, its distribution is rarely confined to any particular LEAD. 581 nerve-track. It rarely lasts longer than fourteen days. The prognosis is therefore favorable, and the treatment unimportant —warm baths and, if it should be at all permanent, electricity and strychnia. Encephalopathia Saturnina. Under the name of encephalopathia saturnina are comprised all of those conditions which, depending doubtless upon an affection of the brain, are developed under the influence of lead. By far the most important of these, not only in regard to its fre- quency, but also in regard to its prognostic importance, is the eclampsia saturnina. A description of all of its different forms as separate varieties, as Tanquerel preferred to do, is too discursive ; this has always conduced to the formation of mistaken ideas— which are inclined to identify encephalopathy, or only the eclampsia saturnina, with uraemia—so that too much attention has been bestowed upon a single form, the eclamptic while the closely allied but symptomatically very different conditions of simple coma and other brain symptoms have been scarcely noticed. Encephalopathia saturnina is in every respect the most severe of the forms in which chronic lead-poisoning manifests itself ; hence it is found almost exclusively among laborers whose work favors a copious absorption of the poison, and in them it occurs in a proportionally large number, and often surprisingly early ; of 72 cases collected by Tanquerel, it was developed in 1 in eight days; in 10 in the course of the first month; and in 44 in the course of the first nine months; on the other hand, in only 28 cases was it developed in from one to fifty-two years after the individuals had begun to work in lead. In animals it is very frequent, and in dogs, after experimental poisoning, it is almost always the symptom which last appears. In lead-workers encephalopathy may come on very suddenly after one of the other lead affections, or without the precedence of such, or beginning with the prodroma usual to the disease. The most important of these are violent headache and amaurosis sat- urnina. Less certain symptoms are stupor and apathy or excite- 582 NAUNYN.—POISONING BY THE HEAVY METALS, ETC ment. The true encephalopathy develops with a more or less gradual or sudden increase of sensory disturbances, and the appearance of general or partial convulsions. The symptoms, as already mentioned, are not the same in all cases : sometimes there is simple maniacal excitement with ten- dency to violence, sometimes melancholia with corresponding hallucinations ; in other cases convulsive attacks appear quite early. Sometimes, but on the whole rarely, the convulsions are more partial, whilst at the same time the unconsciousness is more or less completely wanting; in most cases the appearance of acute eclamptic attacks gives the characteristic stamp to the pic- ture ; eclampsia saturnina is the most common and the principal symptom of encephalopathia. The eclamptic attack comes on very suddenly or after the above prodroma ; the attack does not at once reach its greatest intensity in the severity of the convulsion and duration of the coma, but the more severe attack comes on soon after the first mild one has passed off, and the patient has awakened from a short period of unconsciousness. After this one the coma is of longer duration, and after a while, in most cases, it does not cease at all, and the most violent epileptiform attacks follow one another in rapid succession. According to Tanquerel eclampsia saturnina is never preceded by an aura. Between the attacks there is frequently uneasiness and delir- ium, instead of coma. Thus the case may last for several days. Where the attacks are very frequent, death usually takes place rapidly; in mild cases the attacks are less frequent, and in the interval conscious- ness, at first temporary and incomplete, gradually becomes fully established, or the patient may awake from a very severe attack like an epileptic from a paroxysm, and thus complete recovery ensue, which, however, not unfrequently, soon gives way to a relapse. Amaurosis is the most important of the symptoms accom- panying encephalopathy ; it may, as Tanquerel says, come on before, with, or after the attack of encephalopathy, often sud- denly, but in some cases gradually, sometimes also quite inde- LEAD. 583 pendently of the encephalopathy. The appearances are, accord- ing to ophthalmologists: normal fundus oculi, normal bounda- ries of the field of vision, and central scotoma. Albuminuria is not rare in cases of encephalopathy; its impor- tance is twofold, and not always easy to determine, since albumi- nuria may come on as a result of the convulsions, as in severe epileptic paroxysms, and in a majority of cases it does not depend upon true nephritis. Chronic nephritis is, however, quite frequently observed in lead-poisoning. This symptom may, therefore, in many cases, add to the difficulty of a diag- nosis. Post-mortem exetminedions in cases of lead encephalopathy have been quite numerous, but have, up to the present time, given entirely negative results. The prognosis is always unfavorable ; the worst form is the eclampsia, and in it the prognosis depends upon the severity, and above all, upon the frequency of the attacks. Tanquerel, who, it appears, observed a relatively small mortality, had 16 fatal cases out of 72 of the disease ; other authors give a much higher death-rate. Treatment is entirely without avail, and the expectant treat- ment has, according to Tanquerel, the best success. Theory of the Action of Lead and of Lead-Poisoning, The theory of lead-poisoning has, both in former times and recently, been the subject of much speculation and experiment, but it has as yet been absolutely impossible to give a satisfac- tory explanation of the nature of the disease, based upon facts, and taking into consideration only those symptoms most fre- quently observed. And the value of the important work of Heubel consists chiefly in showing the insufficient foundation of certain attempted explanations, which had unjustly acquired general approval. The view, which has recently gained some notoriety, is this: that the preparations of lead act chiefly upon the muscular fibre, especially the unstriped. When, by the gradual introduction of 584 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. the preparation, the blood becomes, as it were, saturated with lead, then the substance extends its action from the blood to the unstriped muscular tissue of the smaller arteries in the intestine and bladder. The contraction of the smaller vessels leads, on the one hand, to an increase of the blood-pressure. As a proof of this is adduced the abnormally hard pulse observed during the attacks of colic (and, according to Traube, at other times). On the other hand, it leads to anaemia, and thereby to the many distur- bances of function and nutrition of the organs. In this way is explained the general cachexia, and finally, by anaemia of the brain (Rosenstein), the eclampsia saturnina. The muscular paral- ysis can be explained by the disturbance of nutrition in the mus- cular tissue, which is partly the result of the contracted condi- tion of the smaller vessels (arterial anaemia), and partly due to the direct action of the lead upon the striped muscular fibre. The last assumption was based upon the misinterpreted experi- ments of Grusserow, who found a larger amount of lead in the muscular tissue of animals than in the other organs. An expla- nation of the fact that the lead acted upon some muscles and not upon others was attempted by supposing that possibly some existing peculiarities in the supply of blood-vessels to the affected muscles might favor this (Hitzig). The assumed action of the lead upon the unstriped muscular tissue of the intestines and bladder served to explain in a quite satisfactory manner the ap- pearance of the colic. The paroxysmal character of the more violent symptoms of lead disease, in spite of the gradual, long-continued introduction of lead, is explained by considering that, in consequence of the occasional diminution in the elimination of the lead (especially by a diminished secretion of urine), an accumulation of the poi- son in the body takes place. The conclusions of Heubel, which are based upon numerous experiments, and which contradict the above views in almost every particular, must be accepted, and the above theory must be dropped, partly because lacking sufficient foundation, and partly because contradicting the facts. Among the tolerably well-established facts which assist in explaining the nature of the action of lead and lead-poisoning, LEAD. ggg and some of the symptoms of this disease, may be mentioned the following: Lead exists in the blood and all of the organs, as has been already mentioned, in chemical combination with albumen. This is shown by the fact that it cannot be detected by chemical tests without the previous destruction of the organic substances. Hence it is not allowable to ascribe to the lead circulating or re- maining in the system that astringent action which lead com- pounds, especially the acetate, possess. The amount of lead which accumulates in the organs in chronic lead-poisoning is very small, as is also the amount which is eliminated with the urine. Hence it is little probable that the sudden manifestations of lead-poisoning—colic, for ex- ample—are due to the relatively diminished elimination of the lead. On the other hand, it must be acknowledged that noth- ing definite is yet known concerning the separation of lead with the urine in chronic lead-poisoning. The same is true with reference to the amount of lead which is eliminated with the bile, and consequently the importance of the biliary secretion in connection with this question is not yet established. It is also maintained by many that the lead is separated by the skin. This is not established, although but little can be said against such a view from a theoretical standpoint. In all of those cases in which a blackening of the skin, caused by sulphur-baths, is reported, it is not proved that this may not have been produced by minute particles of the lead compound in the form of dust, which had been deposited upon and in the epidermis. The amount of lead which is accumulated in the different organs appears, according to all authorities, and especially from Heubel's latest investigations (reckoned of course in per cent.), to vary very greatly. Heubel found in four experiments upon dogs, poisoned by the administration of the acetate of lead for several weeks, by far the largest amount in the bones, about 0.025 per cent., the next largest amount in the kidneys, 0.012-0.02 per cent., and liver, 0.01-0.016 per cent., next in the spine, 0.006-0.01 per cent., and next in the brain, 0.004-0.005 per cent.; still less was found in the muscles (0.002-0.003 per cent.): in the intestines, after complete separation of their contents, from mere traces to 586 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. 0.002 per cent, was found, and almost always only traces could be detected in the lungs and blood. Hermann rightly remarked that this order of the organs, in respect to the amount of lead which they contain, would be very different if they were consid- ered in reference to the proportion of lead to the inorganic resi- due (after ignition) instead of to the total weight of the fresh tis- sue ; in this case the bones at least would stand much lower in the list. It must be acknowledged at the outset that this knowledge which is gained by experiments upon animals poisoned in a rela- tively short time, and by relatively large doses, cannot, without some allowances, be applied to the much more chronic condition of poisoning in man ; the animals have, however, shown the characteristic symptoms of lead-poisoning. So far, then, as Heubel's results have any value in regard to the theory of chronic lead-poisoning, they show that the known, so to speak, localization of lead-poisoning in the intestines and muscles is not caused by the deposition of the lead directly in these organs. Nothing further is known which can enlighten us as to the constant changes in the organs caused by lead. Of chemical results we have only the interesting one of Heubel's, that in the lead cachexia the amount of water in the organs is increased—a peculiarity which this cachexia possesses in common with others. That the results of anatomical investigations are negative has been already mentioned. It is worthy of notice that there is no hypertrophy of the heart, especially of the left ventricle, which is an argument against the assumption of those who assert that there is, as a result of lead-poisoning, a permanent contraction of the smaller vessels, and consequently an increase of blood-press- ure in the arteries. Those who consider the full and distended pulse as a symptom, not of chronic lead-poisoning generally, but only of the lead colic, are, therefore, probably correct (Tanquerel). Of the single manifestations of lead disease, lead colic is doubtless to be looked upon as a neurosis of the intestinal plexus, but it is impossible to determine whether it is due to central or peripheral causes; yet Hermann certainly goes too far, when he infers that the nature of the affection is peripheral on account of the diminution of the pain upon pressure, since this phenomenon LEAD. 587 is also frequently observed in neuralgias which have a central ori- gin. Whether the pain is due to violent peristaltic action, which is interfered with by the presence of hardened faeces, as Traube thinks, it is impossible to say; at all events, this is partly the cause, yet it must be remembered that the most violent peristal- tic contractions in cases of obstinate constipation and obstruction are not attended with such severe pain as lead colic. Eulen- berg's definition of lead colic should rather be adopted, viz., a mixed neurosis of the iliac and cceliac plexuses. The most important general manifestations which accompany lead colic are not difficult of explanation ; the peculiar hardness of the pulse, with the diminution in frequency, is to be considered as a reflex phenomenon caused by irritation of the sensory fibres of the splanchnic. The arthralgia cannot be explained. There is no doubt that not only muscular contractions, but also direct disturbances of sensibility contribute to it. The nature of lead paralysis, in spite of the numerous and interesting investigations in regard to it, is also not yet explained ; most probably it is a disease of the ner- vous system, and not primarily one of the muscles; at all events, nothing favors the tlieory of primary disease of the muscular tissue, while facts, such as the occasional very sudden appearance of the paralysis, oppose it. Moreover, Westphal's case shows that regeneration after previous degeneration of the nerve-tissue may take place in this disease. Much more difficult of solution is the question, whether the disturbances in the nervous system are of central or peripheral origin. Authors generally incline to the opinion that their origin is peripheral. Yet it is clear that the phenomenon, the observation of which in paralyzed muscles has mainly given rise to this opinion, can contribute nothing to the solution of this question—I mean the so-called reaction of de- generation.1 Although at one time neuropathologists inclined to view it as undoubted proof of the peripheral origin of the paraly- sis, yet we know to-day, especially from Erb, that this reaction is not infrequent in paralysis having a central (spinal) origin. The same is true of atrophy of the muscles, which develops so 1 See Vol. XI. of this Cyclopaedia, p. 426. 588 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. rapidly in lead paralysis; in this respect, also, observations multiply daily, which prove that it is a very common thing to see a rapid development of atrophy of the paralyzed muscles in diseases which certainly have a central, and especially a spinal origin. We mean that in view of these facts the degeneration and regeneration of the peripheral nerves observed in lead paralysis (Westphal's case) does not exclude the supposition of a central affection. On the other hand, it cannot be denied that many things favor the supposition of such central (spinal) affection, such as the frequent symmetry of the disease and the localiza- tion of the paralysis, chiefly noticeable at the beginning, in groups of muscles more closely related functionally than by then dependence upon one and the same periphereal nerve- trunk. There is no doubt that we do have to deal with functional disturbances of the nervous system having a central origin in encephalopathia saturnina in its different forms. And it is yet too soon to form any more acceptable theories concerning the mechanism or chemistry of these disturbances. To say that anaemia of the brain is the cause of them is no explanation; since there is neither evidence of any special brain anaemia, nor do we see anaemia of the brain, when due to other causes, act in the same manner. The most important form of encephalopathy, the eclampsia saturnina, may, in some cases in which nephritis exists, as it not rarely does in lead-poisoning, be explained as due to uraemia; but there is no doubt that in the majority of cases of lead eclampsia this explanation will not answer. In every respect the aspect of encephalopathia saturnina has much in common with chronic alcoholic intoxication, to which the name of encephalopathia alcoholica might well be given. In this disease also we have numerous interchanges of psychoses of dif- ferent kinds, with eclamptic conditions and even genuine epilepsy. It should be added, also, that amaurosis of precisely the same nature occurs in both of these forms of chronic poisoning. The analogy to which we refer here is not altogether without value for the understanding of the nature of encephalopathia satur- nina. Altogether too much stress has been laid upon the sup- copper. 589 position that all of these symptoms of chronic lead-poisoning depend directly upon the lead which is taken into the system and deposited in the organs. In chronic alcoholism it has been an accepted view for a long time, that an abnormal nutri- tion of the whole system is developed in consequence of the long- continued circulation of the foreign poisonous material in the body. The functional disturbances, which finally ensue as a result of the poisoning, stand, therefore, only in very indirect relation to the poison. But why the nutrition of the central nervous system suffers in such a way that these disturbances of its function develop, is thus far an enigma. The relation of lead encephalopathy to the poison absorbed should be looked at in a similar manner; and we do not think that anything has been done toward explaining the disease by detecting the presence of lead in the nervous centres. CHAPTER II. COPPER-POISONING. Oppolzer (Schnitzler), Deutsche Klinik. 1859.—Falck, Ibidem.—Lieberkuehn, Pog- gendorfs Annalen. Bd. 86.—Bergeret et Mayencon, Archives de PAnatomie et de Physiologic 1874. In the organs and secretions of the human body copper al- ways exists in combination with albumen, and can only be detected after destruction of the organic matter. On account of the relatively frequent necessity of examining for the presence of copper compounds in articles of food, etc., its easy detection in such cases is of interest. It is sufficient to acidulate the sub- stance in question, such as food supposed to contain copper, with acetic, hydrochloric, or sulphuric acid, and introduce a polished steel needle, when the copper, even when only a minute amount is present, is deposited upon the needle, and may be easily recognized, since it dissolves in a little dilute ammonia with a blue color. Instead of acidulating the suspected sub- stance, the needle may be moistened with acetic or dilute hydro- chloric or sulphuric acid. 590 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Metallic copper itself is but slightly poisonous, since it is attacked with difficulty by the gastric juice. So far as known, there exists but one well-authenticated case of poisoning by it (copper coin). The oxide of copper, the carbonate (Brunswick green), the sulphate (blue vitriol), the basic acetate (verdigris), the chloride of copper, and the salts of copper with the fatty acids are poisonous. Acute Copper-Poisoning. Among the sources of copper-poisoning the principal are the formation of the fatty salts or acetate, etc., by boiling or pre- serving food in copper vessels which have not been tinned, or which have been badly tinned. Numerous cases of poisoning have been caused in this manner. In the Vienna General Hos- pital there were 130 cases of poisoning caused in this way, 9 of which were fatal. This is, however, not the only way in which a dangerous amount of copper may get into food: many fruits, in order to impart to them a beautiful green color, are boiled after the addition of a small amount of some copper com- pound. Confectionery may be colored by covering with some copper pigment. Oysters in beds in or near copper deposits contain occasionally a considerable amount of copper. Crabs, pickles, and tea may be colored with copper. Eating bread to which sulphate of copper has been added, and the use of spoons made of an alloy containing a large amount of copper have caused acute poisoning. It should be especially mentioned that all of these poisonings may become dangerous to life, even when the amount of copper is not large enough to be clearly perceived by the taste. The inhalation of the dust, which resulted from pressing the gilt letters upon the covers and backs of books in bookbinderies, has given rise to one case of acute poisoning. Cases have been observed where the poisoning was caused by taking Radermacher's oxide of copper and, at the same time, eat- ing acid fruits, but more frequently by the careless use of the sulphate. The sulphate and acetate are used exclusively for criminal COPPER. 591 and suicidal purposes; but the extremely disagreeable taste of these preparations acts as a check to their use for the former purpose. There is much disagreement in regard to the amount which is a dangerous or fatal dose. According to some, doses not equal in amount to the maximum dose of the sulphate of copper of the German pharmacopoeia (less than fifteen grains) have proved dangerous. In other cases much larger doses, up to nearly an ounce, have been taken without injury. The dose of the acetate appears to be the same as that of the sulphate. The symptoms of acute copper-poisoning are in most cases those of a severe gastro-enteritis; the existence of great tenes- mus and pains in the large intestine are noted as peculiar symp- toms in many cases. In comparatively many cases the nervous centres sympathize in a very marked degree, as shown by the violent delirium, etc. Convulsions are also not unfrequently observed; these symptoms are, however, noticed chiefly in those cases of copper-poisoning caused by food, etc., in which the diagnosis is often not perfectly clear. Many authors mention the comparative frequency of icterus. It appears that Christison's authority alone shelters this state- ment. One case of acute copper-poisoning with icterus is men- tioned by Orfila. The result is favorable in by far the majority of cases. Fatal cases generally run a very acute course. It is not certain that chronic poisoning may result from an attack of acute. Yet it is thought ('< Schnitzler—Oppolzer, v. Hasselt) that a scorbutic con- dition may result from a protracted case of acute poisoning. The post-mortem appearances consist of very intense inflam- mation of the mucous membrane of the stomach ; not rarely this change extends downwards into the duodenum and upper part of the small intestine. In cases of poisoning by the sulphate of copper or verdigris the blue or green color of the coating formed upon the mucous membranes is quite characteristic; in the lat- ter case, if it be moistened with ammonia, a deep blue color is formed ; the same is true of the contents of the stomach and intestines. The bodies of those who have been poisoned with 592 NAUNY'N.—POISONING BY THE HEAVY METALS, ETC. copper compounds have in a few instances been found in a mum- mified condition. Treatment.—The most useful antidotes are albumen and cal- cined magnesia. Sugar is much recommended. So far as the theoretical merits of this remedy are concerned, only those varie- ties which easily act as reducing agents (grape-sugar, honey), and not cane-sugar, can be of value; but even the success of these varieties is not sufficiently established theoretically or empirically. Formerly there were recommended as antidotes, without, so far as known, having ever been tested practically, sulphide of iron, iron filings, silver filings, etc., and also the ferrocyanide of potassium. Chronic Copper-Poisoning. The existence of chronic copper-poisoning cannot be doubted, although in the description of it given by authors there is much that is not well established. In the first place, there is an im- portant obstacle to the observation of pure cases of poisoning, namely, that in almost all cases of chronic copper-poisoning other metals, such as zinc, tin, lead, and others, play a part. One fact, which testifies against any powerful poisonous action of the metal, is that the majority of workers in copper and its compounds remain perfectly healthy. Cases of chronic copper-poisoning are reported among copper- smiths, copper-smelters, brass-workers, workers in bronze, etc.; and they have certainly been observed as a result of the continued eating of food rendered poisonous by being prepared in copper utensils. The more certain symptoms of chronic copper-poison- ing are a more or less severe chronic gastric and intestinal catarrh and colic, which may be distinguished from lead colic by the fact that there is scarcely ever retraction of the abdomen, and rarely constipation, but, on the contrary, there is usually diarrhoea. Moreover, according to Oppolzer, the patient with copper-poison- ing does not perceive the sweetish astringent taste peculiar to lead-poisoning, but the taste is the same as that produced by an old copper coin upon the tongue. copper. 593 The presence of a line at the junction of the teeth and gums, similar to that observed in lead-poisoning, is frequently men- tioned. According to some this is exactly the same as the lead- line, according to others it is purple-red in color, while, accord- ing to others, the appearance of such a red line is due to the strong contrast between the red color of the gum, especially marked at the edge of the teeth, and the greenish deposit which colors the teeth even to the gum. Frequently there is a peculiar reddish or greenish coloration of the hair and of the skin, which is probably due to the deposi- tion of small particles of copper, or of the fatty salts of copper. There are no very marked disturbances of nutrition in copper- poisoning, except in those cases in which there is a gastro-intes- tinal catarrh. Mention is frequently made of the existence of special functional disturbances of the liver, yet I have never been able to satisfy myself of the correctness of these assertions. Only one well-authenticated case of copper paralysis is known to me (Oppolzer). In this case the paralysis affected the right upper extremity, and was very similar to lead paralysis. Post-mortem examinations show nothing characteristic ; men- tion is made of a green coloration of the soft tissues and bones, but that this is due to the presence of copper is not surely estab- lished. Treatment. The treatment of chronic copper-poisoning is the same as that of chronic poisoning by the other heavy metals ; no antidote is known. Theoretical and Experimental Considerations. The sulphate of copper gives with albumen a precipitate, which is, according to Lieberkuehn, an albuminate of copper, and contains 4.6 per cent, of copper. Therefore, the salts of cop- per should be absorbed in this form. The different organs of the human body frequently contain traces of copper, as has been shown, especially by Orfila, in the liver ; this amount of copper VOL. XVII.—38 594 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. is, however, very small. Orfila, for instance, was obliged to take several livers together for analysis, in order to be able to demon- strate to the Academy the presence of copper in them. Copper has not been detected with certainty in normal urine. Patho- logically, copper is found to the largest extent in the liver, and is eliminated with the bile. It has been found in many cases in the kidneys. According to Bergeret and Mayencon, after the administration of small doses of copper compounds, it appears in the urine even without the latter containing any albumen. Solutions of the sulphate injected into the veins act as an emetic. In regard to its action as a drug little has been determined experimentally. Falck and others found that it exerted a pow- erful action upon the heart, producing death by paralysis of this organ, and in addition it produced paralysis of the muscles gen- erally. CHAPTER III. ZINC- AND CADMIUM-POISONING. Meyhuyzen, Archiv der gesammten Physiologie. Bd. Yll.—Michaelis, Archiv fiir physiologische Heilkunde. Jahrgang X.—Honssell, Klin. Wochenschrift, 18C6. —Marme, Henle und Pfeuffer's Zeitschrift. Bd. 29. Zinc is detected in the organs and secretions after destruction of the organic matter. In using potassic chlorate and hydro- chloric acid the operation should be conducted over a water-bath, since the chloride of zinc is somewhat volatile. In incinerating; the organs, sulphuric acid should be added in slight excess in order to prevent the formation of the likewise volatile metallic zinc (Michaelis). After destroying the organic matter, and pre- cipitating with sulphuretted hydrogen, Michaelis recommends fusing the white precipitate with cobalt; a beautiful green color indicates the slightest trace of zinc. Of the compounds of zinc, the sulphate and the chloride are the principal ones to be considered; at least these are the only ones which are known to have given rise to acute poisoning. As ZINC. 595 a source of chronic poisoning, is to be especially mentioned the oxide of zinc, which is easily soluble in the gastric juice (hydro- chloric or lactic acid); even metallic zinc is so easily attacked by weak acids, such as those in fruits and the fatty acids, that it may readily become the source of chronic poisoning, as when food is cooked or preserved in zinc utensils or those which have a zinc coating. Rain-water collected from zinc roofs always con- tains, according to Pettenkofer, a considerable quantity of zinc. The carbonate of zinc was formerly much used in the treatment of nervous diseases, and in this way has frequently caused chro- nic poisoning ; which has also been met with in manufactories of zinc white. The chloride and sulphate of zinc have been used with criminal intent, but more frequently accidentally. In one case death was caused by the external application of chloride of zinc paste as an escharotic. Acute Zinc-Poisoning. The amount of any of the zinc compounds necessary to pro- duce acute poisoning is difficult to determine. From fifteen grains to a drachm of the sulphate of zinc is occasionally used therapeutically as an emetic. Fatal results only followed after taking an ounce or more. The chloride of zinc is the most pow- erful, and is, as is well known, a genuine escharotic, while the sulphate is classified among the non-corrosive but irritant poi- sons. Poisoning by this substance is not very rare, especially in England, and is almost always fatal. The very strong metallic taste is said to be peculiar to acute zinc-poisoning. As would be expected, the symptoms of gastro- enteritis are present to a greater degree in poisoning by the chloride of zinc. In these cases the symptoms of corrosion of the upper portion of the alimentary canal are strongly marked: bloody vomiting, visible corrosion of the lips and mucous mem- brane of the mouth, etc. On the whole, the more intense forms of zinc-poisoning are very similar to those of tartar-emetic poi- soning, and both frequently and in an unexpected manner ter- minate favorably. In most cases recovery takes place quickly in 596 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. the course of two or three weeks at the longest, while an unfa- vorable termination may take place later, occasionally with ner- vous symptoms which are little characteristic ; in cases of poison- ing by the chloride of zinc there is frequently observed, three or four weeks after the occurrence of the poisoning, a recurrence of the gastric symptoms, even after apparently complete recovery. This is not rarely noticed after poisoning by the powerful corro- sives, and is probably due to the development of large ulcers or cicatrices upon the mucous membrane of the stomach. In one case of severe chloride of zinc poisoning, which terminated in recovery, Honssell observed during several days great albumi- nuria and haematuria. Post-mortem Appearances. In poisoning by the sulphate of zinc, the appearances pecu- liar to a corrosive action are wanting completely, and there is only seen here and there moderate inflammation of the mucous membrane, which is covered with a tough white mucus. In chloride of zinc poisoning the appearances of corrosion are very marked, and often ulceration and cicatrization of the mucous membrane of the stomach are seen, and in one case there has been observed considerable contraction of the pylorus. Exten- sive gangrene of the wall of the stomach and oesophagus has been noticed. Treatment. Albumen and milk should be given, and the expulsion of the albuminate of zinc formed should be hastened; large amounts of the carbonates and phosphates are the best anti- dotes. Decoctions containing tannic acid are recommended in order to form the slightly soluble tannate. The ordinary treat- ment of simple or ulcerative gastritis must be resorted to if necessary.- ZINC. 597 Chronic Zinc-Poisoning. As already mentioned there are numerous cases recorded of chronic poisoning in zinc mines and manufactories of zinc prepa- rations caused by the vapor and dust. Most of these are not certainly cases of pure zinc-poisoning, since other metals which are impurities in zinc frequently take part. In this manner, cop- per, lead, and even arsenic, may exert their effects. The pos- sibility of chronic zinc-poisoning, however, cannot, according to Michaelis' investigations, be doubted, and its existence has been proved by the occurrence of cases caused in former times by the therapeutic administration of zinc compounds. In these cases the long-continued use of relatively large doses in epilepsy, etc., has led to symptoms of chronic gastro-intes- tinal catarrh with marasmus which gradually reaches a high grade. The description of those cases of chronic zinc-poisoning which occur in factories shows them to be very similar to those of chronic lead-poisoning: dyspepsia, emaciation, colics, with con- stipation, but most generally with diarrhoea, muscular pains and contractures were present; at the same time it is very diffi- cult to exclude the simultaneous influence of lead. Certainly the poisonous influence of the dust and vapor is very slight, since cases of poisoning are quite rare, although the dust is developed in enormous quantities. Treatment of Chronic Zinc-Poisoning. Cases of chronic zinc-poisoning are described as easily cura- ble even when far advanced. Sulphur baths are recommended as the most effective means. No use has thus far been made of potassium iodide. Melsens' experiments speak very favorably of its beneficial effects. TJieoretical and Experimental Considerations. The sulphate of zinc, and apparently the other zinc salts also, forms with solutions of albumen an albuminate of zinc, 598 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. which contains, according to Lieberkuehn, only traces of sul phuric acid and a tolerably constant proportion of the oxide or zinc (4.7 per cent.). In this form the salts of zinc are probably absorbed into the blood and exercise their power, since vomiting takes place as readily after the ingestion of the albuminate as of the other salts. Vomiting and the other symptoms of the action of zinc are observed also after the subcutaneous injection and injection into the veins. In the organs zinc can only be detected in combination with albumen. Michaelis found it in largest amount in the bones and in the liver, also in the brain and in the muscular tissue. The bile seems to contain a relatively large amount. After taking moderately large amounts the zinc can only be detected in the urine after four or five days. The elimination with the bile increases, according to Michae- lis, with the duration of the poisoning, but is not sufficient to separate the metal quickly from the body. Orfila found zinc in the liver sixty days and more after the discontinuance of its use. Experiments as to the action of zinc have shown that chronic gastritis and even ulceration follows the ingestion of the oxide of zinc. After using it for several weeks there occur general convulsions, accompanied by peculiar twitching of the limbs. Meyhuyzen found, as the action of the acetate of zinc given subcutaneously in doses of from one-thirteenth to one-sixth of a grain, rapid (complete in thirty minutes) destruction of reflex excitability. The action of sulphate of cadmium and other cadmium salts appears to be the same as that of the zinc compounds, only, on the whole, more energetic. Severe cases of poisoning are said to have been caused merely by the inhalation of the dust. Half a grain of the sulphate of cadmium is said to produce vomit- ing easily. SILVER. 599 CHAPTER IV. SILVER-POISONING. Bael, Gazette mgdicale. 1865.— Frommann, Virchow's Archiv. Bd. 17.— Riemer, Arch, fiir Heilkunde. Bd. lG.—Lionville, Gazette mgdicale de Paris. 1868.— Bogoslowski, Virchow's Archiv. Bd. 46.— Scattergood, British Medical Journal, 1871.—Buguet, Gazette mfidicale de Paris. 1874.— Rouget, Arch, de Physiolo- gic norm, et pathol. The detection of silver in the tissues and secretions is accom- plished after the destruction of the organic matter. When pres- ent in the organs in large amount it can usually be detected microscopically ; in such cases it is deposited apparently as a metal, in the form of fine dark granules. Practically, the nitrate of silver only need be considered. Cases of poisoning by it may be acute or chronic. 1. Acute poisoning by nitrate of silver (lunar caustic) is rare ; in the majority of cases it is caused by the breaking off and swallowing of pieces of the caustic during cauterization of the throat; very rare are cases of poisoning caused by the ingestion of solutions of nitrate of silver taken with suicidal intent or acci- dentally. The fatal dose is not fixed. Nearly one ounce in solu- tion has been taken without fatal result, and doses of nearly fifteen grains daily were formerly given therapeutically. The symptoms are those of corrosive gastritis, with occasionally cere- bral disturbances. In one case (that of a child), death occurred at the end of nine hours. Post-mortem appearances. —Inflammation in the upper part of the alimentary canal, extending downwards to the jejunum, the affected parts being blackened. 2. Chronic poisoning.—This is observed only as the result of the medicinal use of nitrate of silver, usually from its internal administration, but also from long-continued application of it to the throat as an escharotic, some of the fluid being swallowed. In the first case well-defined symptoms are not produced until its 600 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. use has been continued for months, and from two and a half drachms to three ounces have been taken. The first sign of chronic silver poisoning is the appearance of a bluish line upon the gums similar to that produced by lead. The most important symptom is the so-called argyria—that is, the discoloration of the skin and mucous membranes. The skin assumes a grayish-blue color of greater or less intensity, which color is, as a rule, deeper on the cheeks, and generally on those portions of the body exposed to the light. The color increases in intensity for some time after the discontinuance of the remedy. In addition to this peculiar color, symptoms of chronic gas- tro-intestinal catarrh and, in some cases, albuminuria have been observed as results of chronic silver-poisoning. The discoloration is very permanent, and may last for years without change. Post-mortem examination shows that the discoloration is not limited to the skin and superficial mucous membranes, but may extend to the liver, spleen, kidneys, intestinal mucous mem- brane, etc. Microscopic examination shows a deposit, probably of metallic silver, in the form of very fine granules, in the most superficial layers of the corium, in the sweat-glands, in the smooth muscular fibre, and in the capillaries of the skin. In the internal organs the deposit is chiefly in the walls of the smaller arteries, to a less extent in those of the veins, sometimes in the capillaries, the Malpighian corpuscles of the kidneys, etc. An abundant deposit of silver is also found in the interstitial tissue of the lymph-glands (mesenteric). The epithelium of the skin, as well as that of the internal organs, remains free to a marked extent. Theoretical and Experimental Considerations. According to Lieberkuehn, the nitrate of silver forms, when added to a solution of albumen, an albuminate of silver which contains 6.5 per cent, of silver. It is assumed by some that the silver is absorbed as such. There is no doubt that the albumi- nate of silver acts as a poison when it is injected or when it is MERCURY. 601 taken internally, but the manner in which it acts is not yet fully established. On the other hand, Riemer shows that by far the largest part (as much as nineteen-twentieths) of the nitrate of silver introduced into the stomach, as when taken medicinally, does not act as such, but is reduced in the stomach into an in- soluble form, probably to metallic silver. R. considers, there- fore, that in argyria the question is chiefly concerning the depo- sition of the silver granules already existing in the intestine. In opposition to this it should be observed that the distribution of the silver granules in that case is not similar to that of other pig- ments introduced into the body. At all events, we cannot, as was formerly done, refer the discoloration of the skin entirely to the reduction of the silver under the influence of light, although this was, perhaps, in some cases, noticeable, on account of the deeper color in those parts of the skin which were exposed to the light. Silver has been detected chemically in the organs in such cases of argyria. Silver is eliminated with the urine in cases where it has been administered for a long time, and even for some time after its administration has ceased. Treatment. In acute poisoning the white of eggs and milk should be given. Common salt is an antidote. It should be remembered that, when solid pieces of the poison have been swallowed, an attempt should be made to dissolve them. Nothing is known concerning the treatment of argyria. CHAPTER V. MERCURIAL POISONING. Overbeck, Mercur u. Syphilis. Berlin, 1861.—Kussmaul, Untersuchungen fiber den constitutionellen Mercurialismus. Wurzburg, 1861 .—Baerensprung, Annalen der Charitg, VII. 1856.— Voit, Physiologisch-chemische Untersuchungen. Augsburg, 1857. — Waller, Prager Vierteljahrschrift. 1859 und I860.—Lorinser, 602 NAUNYN.—POISONING BY THE HEAVY METALS, ETO. Wiener medicinische Wochenschrift. 1859 u. I860.— Oettinger, Ibid. 1859.—v. Boeck, Zeitschrift fiir Biologie. 1869.—Saikowski, Virchow's Archiv. 37.—®. Oettingen, De Calomelanos, etc. Dorpat. Dissert. 1848. In cases of poisoning mercury cannot be detected in the organic fluids and tissues by the ordinary reactions, until after the destruction of the organic matter by hj^drochloric acid and potassium chlorate; in performing this operation too high a temperature must be avoided, since all of the compounds of mercury are very volatile;—this process should be conducted over a water-bath at a moderate temperature. For the same reason the organic matter cannot be destroyed by incineration. From the fluid thus obtained the mercury can be isolated by the methods used in inorganic analysis. The use of electrolysis is very highly recommended by Overbeck and others : the pas- sage of a galvanic current (2-10 Bunsen or Grove cells) through a solution containing only one part of mercury in 40,000, gives a very plain coating of mercury upon a small gold plate attached to the negative electrode. Schneider was able to detect in this way one-sixth of a grain of corrosive sublimate dissolved in 500,000 times its weight of water. A piece of copper foil in the place of the gold foil gives a little less delicate results. In either case the nature of the deposit upon the metal should be tested by sublimation. For this purpose it should be intro- duced into a glass tube closed at one end. Upon the applica- tion of heat the deposit disappears from the metal, and is con- densed upon the cool part of the tube in the form of a metallic mirror. This operation should be performed immediately after the deposit has been obtained by electrolysis, since otherwise the mercury might volatilize spontaneously. Mayengon and Bergeret have recently recommended for the detection of mer- cury a very simple electrolysis ; moreover, they do not pre- viously destroy the organic matter. So far as we know, their methods have not been confirmed by other investigators. Stannous chloride precipitates the mercury, which always exists in the fluids resulting from the decomposition of the or- ganic matter as corrosive sublimate, in the form of calomel, and, if an excess of the reagent has been added, in the form of metal- MERCURY. 603 lie mercury; by means of this reagent mercury may be detected in solutions containing only one part in 40,000. The poisonous action of mercury and its compounds is mani- fested in very different ways; and this difference is not well defined by distinguishing between an acute and chronic form. 1. The Corrosive Action of Mercurial Preparations upon the Intestinal Tract. Corrosive sublimate is almost the only preparation of mercury which is the cause of dangerous corrosion, and this may be taken as the type of the other mercurial compounds which have a simi- lar action. It is rarely used with criminal intent, more frequently with suicidal, and very rarely is it the cause of cases of acciden- tal poisoning. Excepting this compound, mercuric nitrate is the most frequent source of accidental poisoning. In its action it scarcely differs from corrosive sublimate. Corrosive sublimate is soluble in water, alcohol, and ether. It produces a precipitate in solutions of albumen even when very dilute. This precipitate appears to be a mercuric albuminate (see below under "Theoret- ical Considerations"). The powerful corrosive action of the sublimate seems to depend upon this property of uniting chemi- cally with albumen. The smallest fatal dose of corrosive sublimate is given as a little less than three grains for a child, and also for an adult. On the other hand, it is said that sometimes, and especially after its habitual use, as, for example, in the sublimate eaters of the East, enormous doses can be taken without injury ; in the same way it is said that an opium-eater, in addition to his usual quan- tity of opium, has taken daily two scruples of sublimate. The ingestion of corrosive sublimate in the same way as that of opium appears to be quite common, and its action to be similar to that of opium, only more exciting. Clinical History. On taking corrosive sublimate, its peculiar sharp and metallic taste will usually be noticed; it produces powerful corrosion of 604 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. the mucous membrane of the mouth, oesophagus, stomach, and intestines, and leads rapidly to gastro-enteritis of the severest form. Pain is felt in the mouth, throat, oesophagus, and stomach, and there is violent vomiting and diarrhoea characterized by nu- merous discharges which are attended with painful tenesmus. These are more frequently bloody than in arsenic-poisoning. In addition there is suppression of urine, often complete anuria, so that in two and even- more days not a drop of urine will be passed—in arsenic-poisoning this rarely happens to the same extent; there is also the greatest prostration, and all of the symptoms of collapse, etc. In many cases the corrosive action of the poison affects the larynx, producing hoarseness and dyspnoea. The progress of the case is usually very rapid. In one case (Taylor) death took place in half an hour ; more frequently it occurs in from two to twelve hours, but in most cases after twenty-four hours. Rarely life is prolonged for ten or twelve days. In those cases in which the patient lives more than tAven- ty-four hours, salivation frequently occurs, but this may be en- tirely wanting. A favorable termination can scarcely be hoped for in the severer cases, where treatment is not resorted to immediately; in this respect, of course, in addition to the size of the dose, the condition of the stomach, whether full or empty, is an important feature. The post-mortem appearances are those of corrosive gastro- enteritis ; the mucous membrane of the mouth, throat, and oeso- phagus is inflamed, wrinkled, and covered with a white coat. The mucous membrane of the stomach is in some places, espe- cially near the pylorus, converted into dark, very tough eschars. In some cases ulceration takes place; after separation of the eschars there may be perforation. Here and there particles of the substance used may be found adhering closely to the mucous membrane. In the small intestines the appearances are usually normal, but in the large intestine, on the contrary, severe inflam- mation, even to ulceration and hemorrhage, has frequently been noticed. This last appearance is to be looked upon as the begin- MERCURY. 605 ning of the general action of the mercury. In acute mercurial poisoning, mercury can usually be detected in the organs, but cases are known where death did not take place until the fourth day or later, in which not even a trace of mercury could be found in the organs, stomach, or contents of the intestines. Treatment— Freshly precipitated hydrated ferrous sulphide (Bouchardat and others), prepared by adding alkaline sulphides to a solution of ferrous sulphate, is the only substance which is universally acknowledged as a positive antidote, but it can rarely be obtained quickly enough. When vomiting has not taken place immediately, it should be produced by mechanical irri- tation, subcutaneous injection of apomorphia, etc.; the corrosive action of the sublimate should be counteracted by giving large quantities of milk, etc. It must not be forgotten that the com- pound of the mercury with the albumen thus formed (see above) is soluble, and must be removed. The use of the stomach-pump has been pretty generally, but probably erroneously, condemned, for fear of possible perfora- tion on account of the great corrosion of the oesophagus and stomach. 2. Mercurial Poisoning by Absorption of the Poison into the Circulation. —Constitutional Mercurial Poisoning. With the exception of cinnabar (simple sulphide of mercury), which acts only in the form of vapor, all of the preparations of mercury, when'taken into the system, have a poisonous action. The only doubt about this is in regard to metallic mercury.1 The experiments of Overbeck, however, seem to have settled this question. These were made with mercurial ointment. Ac- cording to these investigations and those of others, there is no doubt that, when energetically rubbed into the skin, the finest particles of mercury penetrate into the subcutaneous cel- lular tissue, and thence into the circulation in large amount; yet the action of this ointment has been ascribed to the fatty mercurous salts which it always contains. This may, doubtless, 1 See Hermann, Experimented Toxicologic. 606 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. explain a part of the action of old ointment (which contains a large amount of mercurous salts), but Overbeck found too slight a difference in the action of such old ointment and that freshly prepared from chemically pure metallic mercury, to be able to disregard entirely the action of the absorbed metal. The fact that metallic mercury can be taken into the stomach in large amounts, from three to nine ounces and more, without giving rise to poisoning, shows only that the metal is harmless in those cases in which a small surface is exposed to the oxidizing action of the system. The ways in which mercury may get into the body are very various. First in importance are its therapeutic uses. Mercu- rial ointment is a form much used at the present time ; also the subcutaneous injection of corrosive sublimate solutions, and the internal administration of calomel, less frequently of corrosive sublimate (Dzondi), play an important part. Many other mer- curial preparations are still used internally by older physi- cians, such as mercurous iodide (hydrargyri iodidum viride, U. S., Br.), and much more rarely mercuric iodide (hydrargyri iodidum rubrum, U. S., Br.). In England metallic mercury is much used internally in the form of blue-pills. Externally many different preparations are used, according as they are more or less irritant, in the form of plasters, and corrosive sublimate solutions are frequently added to baths and poultices. Inunc- tions of cinnabar are rarely used at the present time. All of these methods may give rise to the most severe mercurial poi- soning if employed energetically enough; even applications to the undenuded skin may have this effect, which is produced much more readily if the application is made to an ulcerated surface. In the use of mercury in the arts, in addition to the dust which contains particles of mercury or a mercurial compound, we must consider the vapor of mercury as of the most impor- tance, especially when the work is performed at a high tempera- ture, but also even at a very low temperature. Those Avho are, by virtue of their work, most endangered are workers in quicksilver mines and smelting works, manufacturers of mirrors, gilders, manufacturers of thermometers, percussion-caps, etc.; in a less MERCURY. 607 degree hatters, bronzers, and furriers. Some time ago much excitement was created by the accidents which happened to sail- ors upon certain vessels in which during the voyage jars, con- taining metallic mercury, became leaky; the mercury, which was spilled in the hold of the vessel, gave rise to the most severe symptoms of poisoning. Those cases are similar in which, in working with mercury, the metal accidentally falls to the floor and gets into the cracks. Cases of mercurial poisoning, as a result of this apparently, are not rare. In the same way persons have been poisoned from living in rooms in which mercury was spilled many years before ; also persons who live in the neighbor- hood of rooms thus infected. It does not appear that the public is at all endangered by the illegal use of mercurial compounds for adulterating articles of food, or in the manufacture of articles for general use. The action of mercurial compounds, especially the therapeutic action, varies very much in intensity and in kind ; this variation depending largely upon the conditions—on the one side of the preparation and on the other of the organism—affecting its ab- sorption. The more easily soluble compounds, besides being more irritant, are also more readily absorbed; but those which are sol- uble with the greatest difficulty, like metallic mercury, can also be absorbed, and are by no means absolutely inert as regards the irritant action. With reference to this subject the investiga- tions begun by Buchheim (Oettingen), and continued by Voit and Overbeck, are especially important. All mercurial salts, even metallic mercury itself, are, as already mentioned, when in a state of sufficiently minute sub- division, converted more or less readily by contact with the alka- line chlorides, especially when albuminous compounds are also present, into corrosive sublimate, which is easily soluble and is a poAverful escharotic. This change is apparently hastened by the presence of free hydrochloric acid. As the general action of the insoluble preparations of mercury depends entirely upon this change, so also do many of the local effects ; as, for example, the irritating and purgative action of calomel is solely dependent upon this conversion into corrosive sublimate; in this way very unusual effects of calomel become intelligible. Thus we have 608 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. reports of cases in which most violent and fatal mercurial stoma- titis has been produced by very small doses of calomel ; as, for example, very severe stomatitis, lasting for weeks, with necrosis of the jaw, was produced in a boy eight years of age, after taking once a day for three days a dose of three-fifths of a grain of calomel; in another case a boy fourteen years old (?) died from mercurial poisoning (necrosis of the lower jaw) produced by one dose of five and a half grains of calomel. Many cases are report- ed in which fatal stomatitis has been caused by from six to fif- teen grains of calomel taken during twenty-four hours, or in a single dose. The same is true of metallic mercury. Fatal cases have been reported in England caused by taking, for example, in the course of a week, about fifteen grains of mercury with chalk, or the same amount of blue-pill, which contains at the most only a few grains of mercury. We must assume that in these cases the change of the calomel or the metallic mercury into corrosive sublimate, which usually takes place only to a slight extent, is very much greater, perhaps oAving to the presence of an unusually large amount of free hydrochloric acid, etc. It cannot be denied, however, that in addition to the above-men- tioned points in reference to the poisonous action of mercury and its preparations, different individuals show a very varying suscep- tibility to them. The fact that, of the workmen exposed to the fumes of mercury, some remain entirely free from any injurious effects, bears testimony to this. Furthermore, it can be easily shown that mercurial ointment, applied to the skin of many per- sons, even in very small amount and superficially, as for the de- struction of crab-lice, ahvays produces very severe symptoms. An instructive case is reported by Alfinger (Kussmaul) of a girl who was affected with mercurial stomatitis caused by simply rooming with her sister, who was employed in manufacturing mirrors, and who remained entirely unaffected herself. To explain the above- mentioned cases of poisoning by small doses of calomel, etc., individual predisposition must be taken into account in addition to the other points mentioned. It has been repeatedly stated that young people are more apt to be affected than older ones. Usually the symptoms of poisoning by mercury come on while the individual is still exposed to its action, but it some- MERCURY. 609 times happens that they are entirely absent during this period and do not appear until after removal from its influence. Several cases are reported in which the symptoms which first appeared in the disease were repeated later, and also returned again after the lapse of years without any re-exposure of the individual to the action of the poison. This has been the case with salivation after one attack of mercurial stomatitis, caused either by the use of mercury in the arts or by its therapeutic administration, and is especially true of mercurial palsy. In one case of Kussmaul's there appeared, after handling mercury (making mirrors) for nine months, severe palsy, which, although the patient was removed from the influence of the mercury, constantly recurred Avith varying intensity during a period of twenty-five years. Clinical History. Formerly, and even at the present time, the severest diseases, especially ulcerative diseases of the skin and affections of the bones, have been ascribed to mercurial poisoning. We do not in recent times see affections of the bone occurring as symptoms of the action of mercury, and their existence in former times has never been fully demonstrated. Also special mercurial skin dis- eases, severe ones at least, have not been recorded since Alley's extended reports. The reports and descriptions of the so-called hydrargyria rest in the main, doubtless, upon mistakes and erroneous diagnoses. Eczema is, hoAvever, frequently observed after mercurial poi- soning, but apparently as the result chiefly of the local irritant action of the preparation used upon the skin, or occasionally as the result of copious perspiration, uncleanliness, etc.; but this, and still less the abscesses Avhich sometimes folloAv the subcu- taneous injection of corrosive sublimate, cannot be regarded as symptoms of mercurial poisoning. It should not and cannot be denied that formerly these, as well as all other possible conse- quences of mercurial poisoning, were observed; yet in those cases the condition was not one of simple poisoning, but, in con- sequence of the rashly excessive mercurial treatment, symptoms of poisoning were produced, and, at the same time, the system VOL. XVII.-39 610 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. was reduced to the greatest degree, partly by this treatment, and partly by attacks and influences entirely independent of the mercury. The symptoms which were observed in such indivi- duals, cachectic and usually syphilitic to begin with, could not truly be unequivocal. In the consideration of ordinary constitutional mercurialism we will except entirely those rare cases, in which very acute poisoning is caused by a single application of corrosive sublimate to the skin or to an ulcerated surface. Thus, in the cases of two men, fatal poisoning followed the application of an ointment (one ounce of corrosive sublimate in six ounces of lard) for the itch, and the same number of fatal cases resulted from the application of an ointment consisting of two drachms of corrosive sublimate in an ounce of fat for disease of the scalp. There was, it is true, in these cases a general and not a local action of the poison, for they ran exactly the same course as a case of acute poisoning from the internal ingestion of corrosive subli- mate—that is, with the most violent acute gastro-enteritis and death in a few days; the post-mortem appearances also were exactly the same as in acute sublimate poisoning. If we leave out of account the doubtful results of mercurial poisoning and these forms allied to acute sublimate poisoning, then poisoning by mercury assumes the following simple form: Of the greatest importance is the influence of the metal upon nutrition ; this is rarely wanting when the action of the mercury is severe. Where small quantities of mercury are absorbed du- ring a long period, as in cases where the daily handling of mer- cury, in one's occupation, leads to poisoning, this action of the mercury shows itself usually by a simple ansemia ; this appears more rapidly when relatively large amounts are absorbed in a shorter time, as in the so called mercury cures. In these cases also we have a simple ansemia characterized by a pale color of the skin and mucous membranes, lassitude and malaise combined occasionally, as is frequently the case in ansemia, with so called rheumatoid pains. In other cases this comes on with a more or less intense fever, which is, however, rarely of much consequence. Besides the symptoms due to this, there are usually observable signs of a chronic gastric catarrh and of a genuine enteritis: MERCURY. 611 diarrhoea, often accompanied by very violent colicky pains, tenes- mus, and evacuation of slimy and even bloody discharges. This enteritis is caused as well by the external application of mercury in the form of gray ointment (Brandes) as by the inter- nal ingestion of mercurial compounds. When the general action develops more rapidly, salivation has usually been observed before the appearance of the above symptoms; this is a sign of the specific mercurial affection, stomatitis. This is, however, in an especially high degree, dependent upon whether the proper precautions have been taken to prevent its appearance or not. In cases where this has been done, salivation frequently fails to appear, even when the other symptoms of poisoning are present. Otherwise, or sometimes in spite of all precautions, salivation is sometimes the first symptom of poisoning. It begins almost without exception with an abundant flow of saliva, fetor of the breath, and simultaneous swelling of the gums, upon which, when the affection is severe, there appears a croupous mem- brane ; this is at first lightly attached, but later it adheres more closely and an ulceration of the gum develops beneath it; this can also occur without previous exudation. These changes take place first in those spots where particles of food or the secretions collect and remain, as in the folds of the membrane, at the edge of the teeth, especially when carious or unclean, and in the fold between the gum and cheek. The ulcerations may, when long neglected, or in especially unfavorable cases (more easily in chil- dren and after or simultaneously with a severe acute febrile dis- ease), increase in extent and lead to extensive destruction of tissue, even to necrosis of the jaw. In such cases the disturbance of nutrition may reach to any extent, and a high fever, accompanied with general collapse, may develop, as well as brain symptoms and conditions of a scorbutic nature with tendency to hemorrhages, etc. ; in these cases it can- not be determined exactly how far the symptoms are dependent upon the direct action of the mercury. It is very rare that the above disturbances of nutrition reach to such a dangerous extent in acute mercurial poisoning without the addition of severe stomatitis. Very different is that form of mercurial poisoning which 612 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. comes on very gradually, as in workers in mercury mines, mir- ror and thermometer manufacturers, etc. In these cases the same symptoms usually develop, only more slowly, but unfortunately there are present as signs of mercurial poisoning, often for years, a more or less severe gastric and intestinal catarrh, a gradually increasing ansemia, a moderate increase of the salivary secretion, a peculiar tendency to stomatitis, and the so-called mercurial erethism. The general character of this last symptom is very peculiar. Essentially the condition is characterized by great mental excita- bility of the patient to external impressions. Every unexpected or perplexing event excites him in the highest degree. The visit and conversation of the physician put him into a state of com- plete bewilderment, even to syncope; the adult patient grows pale, and stammers in answering the simplest questions. To perform his allotted task requires the greatest effort, or is even impossible if he sees or thinks that he is being watched. There is also great solicitude and a feeling of anxiety without any rea- son for it. There is sleeplessness, or sleep which is restless, fre- quently broken, and disturbed by frightful dreams, headache, and palpitation. In the severer forms there are frequently hal- lucinations, usually of a frightful nature. When perplexed or excited, traces of tremor are often perceptible in a slight twitch- ing of the muscles of the face at the corners of the mouth. Such a condition of slight intensity may last for years or tens of years, and may then be characterized as an habitual mercu- rialism. Usually after this condition has lasted for weeks, or some- times for years, mercurial tremor comes on. This is very different, especially in its intensity, from the simi- lar conditions which one sees in chronic poisoning by lead and other metals ; when severe, it resembles almost exactly paralysis agitans. It begins in the upper extremities, tongue, and muscles of the face, and extends to the lower extremities. It comes on as a slight quivering, perceptible especially on speaking, and in- creases gradually in violence until complete convulsive twitch- ings are produced. These convulsions, although existing in all parts of the body, differ from the so-called general convulsions MERCURY. 613 by appearing in the single limbs independently. They render locomotion impossible. During sleep the trembling ceases completely ; any attempt to move increases it or brings it on; excitement of any kind, especially mental emotion, also strengthens it. In the severe grades of tremor, paralysis of the affected limbs always occurs. This is always more severe in the lower extremities; it reaches a high degree first in the later stages. Paralysis without tremor scarcely ever occurs; but cases have been repeatedly observed in which, after long duration of the tremor, paralysis occupies the prominent position, the trembling being diminished. In one case, six weeks before death, there Avas observed entire cessation of the tremor and the simultaneous appearance of com- plete paralysis of both legs and the right arm; the paralysis of the arm became better. Kussmaul describes a case in which, after severe mercurial tremor and clonic spasms, permanent pa- ralysis of the right arm developed itself. Ansesthesia has not been observed as a result of the action of mercury ; but, on the contrary, pain, in part purely neuralgic, of the most varying kinds is a frequent consequence of the poi- soning : very violent, even insupportable headache, partly in connection with the stomatitis ; toothache, and maxillary neural- gia ; dragging and tearing pains in all of the limbs without any visible evidence of inflammatory lesion. There is a feeling of op- pression in the chest, increasing even to attacks of asthma, with- out any disease of the thoracic organs being demonstrable. Much stress has always been laid on the mental anomalies in mercurialism, but the cases which have been cited are of very doubtful value, syphilis and other conditions of the greatest importance in the causation of mental diseases playing their part. Yet what has been mentioned above of mercurial erethism shows satisfactorily the peculiar action of the metal upon the mental condition. The mental disease, however, hardly equals the description there given ; at all events, peculiar and well- defined conditions of mental alienation develop themselves very rarely, but tolerably severe mental weakness, Avith diminution of memory, etc., is not very infrequent. The same is true with regard to the existence of apoplexy and 614 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. mercurial epilepsy. Authentic cases of the former appear to be unknown, and cases of true epilepsy have not been established with certainty, although cases of syncope with an aura (epilep- toid syncope) have been observed. Overbeck is of the opinion that it must remain undecided whether these conditions are directly caused by the mercury, or whether it be not the cachexia developing more and more under the influence of the poison that should be considered as their cause. All of these conditions, and also the severe symptoms of mer- cury-poisoning in general, are, if not of too long duration, capa- ble of improvement; yet they may become permanent at any stage; thus the simple, often very severe trembling, due to the action of mercurial poisoning, is most frequently seen remaining through life. In the later stages of the disease it frequently advances in spite of all treatment and of total removal from the influence of the poison, and death takes place with increasing cachexia or supervening phthisis. It frequently recurs in the less advanced cases. Of the complications which occur in persons suffering from mercurial poisoning, and which stand in distant relation to it, must be mentioned first of all pulmonary phthisis, which, ac- cording to Kussmaul's reports, exists very frequently, and causes by far the greatest number of deaths in constitutional chronic mercurialism. Pregnant women are said to miscarry very easily, and children frequently become feeble, scrofulous, or rachitic, or are born otherwise diseased. The existence of saliva- tion or of the tremor in new-born or very young infants, when the mothers were severely affected with mercurial poisoning, is of interest. So far as known, however, the direct influence of the mercury upon the child cannot be excluded in a single case, since the mothers were in all cases, owing to the nature of their occu- pation, exposed to what is termed "professional" poisoning, and it is probable that they carried the metal in their clothing or otherwise, from the shops to their own or their children's room. In those who are severely affected, dropsy may develop itself MERCURY. 615 and prove fatal; nephritis appears to cause this very rarely, although temporary albuminuria is not rare in severe chronic constitutional mercurialism. Theoretical and Experimental Considerations. The constitutional action of all of the preparations of mer- cury, with the exception perhaps of mercuric nitrate, presup- poses their change into corrosive sublimate. That this is the case with metallic mercury and the iodides, as well as with calomel, has been, in spite of many contradictions even at the present time, proved by Voit's experiments, which were based upon the older work of Mialhe. This change takes place, even at the temperature of the body, under the influence of the common salt and the albuminous compounds. Whether these act as carriers of ozone, as Voit thinks, must remain unsettled. Corrosive subli- mate forms with the albuminous substances a mercuric albumi- nate, which is insoluble in water, but soluble in an excess of albumen; in this compound the mercury is probably contained in the form of mercuric oxide. The mercuric albuminate absorbed into the body appears to be distributed through all of the organs, and can frequently, if not always, be detected in them in con- stitutional mercurialism. No quantitative estimations of the mercury in the organs have been reported. Mercury has certainly been found in the liver, when the person had not been exposed to its action for a year. It has been proved by the reports of good observers, that mercury exists relatively very often in the bones in accumulations readily discernible by the naked eye even many years after mercurial treatment. The metal has also been occasionally found in biliary calculi, as I can certify from my own observation. It must not be considered, however, from the finding of metallic mercury in the bones, that the mercuric albuminate taken into the body has been decomposed by reduc- tion of the mercuric oxide and the deposition of the metal, since it is not proved that this condition exists, except when the metal itself has been applied (inunction), and it may very well be a simple accumulation of the mercury which has been absorbed as such, and not converted into the albuminate. Yet it is certain 616 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. that the mercuric albuminate in the body is again decomposed , this is shown by the fact that the mercury is sometimes elimi- nated in urine which does not contain albumen. Frequently, however, we find the urine albuminous when it contains mercury Besides with the urine, mercury is eliminated with the saliva, bile, fseces, and perhaps the sweat. Bergeron and Lemaitre observed an elimination of mercury with the sweat after giving mercuric iodide. Voit asserts that he has observed in the case of a thermometer-maker, who was suffering from severe mercu- rial cachexia, that articles of silver were amalgamated by being in contact with his hands ; Kussmaul, on the contrary, could detect no mercury in considerable quantities of the sweat of a mirror manufacturer similarly affected. This elimination of the metal in the form of the finest globules has been observed in the urine, fseces, and bile, after inunction. The elimination may, as is probable in the case of the urine, be intermittent, and be going on years after the absorption. In other cases, no mercury was found in the organs several weeks, or even only one week, after taking a moderate amount; it is possible, therefore, that the elimination was already completed at the expiration of that time. Little has been determined theoretically or experimentally concerning the influence which mercurial poisoning exerts upon the metamorphosis of tissue in the organism. The investigations of Boeck seem to show that mercury neither increases nor dimin- ishes tissue-metamorphosis in general, but, according to Saikow- ski, who experimented with animals (rabbits and dogs), corrosive sublimate causes an increased secretion and a saccharine condi- tion of the urine of long duration. To mercury, and especially to calomel, has been ascribed the power of increasing the biliary secretion, but this result has not been noticed by most observers experimenting upon dogs with biliary fistulse. Little is known concerning the cause of the single symptoms of mercurial poison- ing. That the stomatitis is the direct result of the inflammation of the mucous membrane by the mercury contained in the saHva is not established, since careful investigators of many cases of mercurial salivation deny that mercury is generally present in the saliva. But the gastric and intestinal catarrh may be the MERCURY. 617 result of the irritation produced by the mercury eliminated into the contents of the intestine, and here, perhaps, changed partly into corrosive sublimate; at all events, the reports of many authors agree in this, that the elimination of mercury in the fseces is abundant and constant. It is not yet determined whether all of the mercury eliminated with the fseces (leaving out of account, of course, that Avhich is taken by the mouth) conies from the bile or not. Nothing is known of those circum- stances which cause the mercurial tremor, etc. In all probability it is due to an affection of the central nervous system, but the nature of this disease produced by the influence of the metal is thus far entirely unknown, and it is not proved that this specific result of the poison is due to the direct action of the mercury upon those portions of the brain whose functions are disturbed by it. It must not be forgotten that the presence of the poison in the diseased organ has by no means been detected in all cases of mercurial tremor, etc. Concerning those diseases which stand in remote relation to mercury-poisoning, such as phthisis pulmonum, which is espe- cially frequent in mirror manufacturers, there is no positive proof that they are the result of a specific mercurial action. The great activity of workers in mercury, with all of the dangerous influences which are associated with such activity, and also the ansemia and cachexia caused by the mercury, are the cause, and not the metal itself. This consideration should have an influence in deciding as to the advisability of employing mercurial treat- ment in many cases. Treatment of Mercurial Poisoning. The prophylactic treatment, of course, varies to an important extent, according to the form in which the poison comes in con- tact with the body. This is not the place to enumerate the means which must be used to prevent the appearance of dangerous symptoms in the energetic employment of mercurial treatment. To prevent professional mercurial poisoning all of those precau- tions should be taken which are generally employed in work- shops where dangerous substances, and especially those giving 618 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. rise to dangerous fumes and dust, are used. First of all we should insist upon the most complete ventilation of the Avork- rooms possible, prohibition from taking food in the shop, cleanli- ness, such as washing the hands and changing the clothing on leaving work, etc., etc. In certain cases it is easy to form an opinion as to whether the conditions of sufficient ventilation are fulfilled, or whether there is danger from the diffusion of mercu- rial vapor or dust on account of defective ventilation in the work- or dwelling-rooms; living flowers serve as the most delicate reagent for detecting such dangerous impurities in the atmo- sphere ; they die very quickly in an atmosphere containing mer- cury. A gold leaf becomes quickly amalgamated in such an atmosphere, and a stick of wood painted with floAvers of sulphur becomes brown on the surface, owing to the formation of sul- phide of mercury. If not successful in keeping the atmosphere free from mer- cury, we would recommend as an experiment the free use of flowers of sulphur in some form, such as strewing it upon the floor, painting the walls with it, or as a sulphur respirator—that is, linen cloths, the meshes of which are filled with sulphur. It appears certain that the action of mercurial vapor upon plants at least is neutralized by saturating the atmosphere with sulphur, on account of the formation of the sulphide of mercury. Recently it has been recommended to saturate the air of the affected rooms Avith ammonia vapor by sprinkling the floor with a strong ammonic hydrate solution after working hours. Expe- rience is said to have found this procedure successful, although chemically it is not yet understood. When the system is being subjected to the action of mercury, good food, and at the same time the use of warm baths, appear to be the best means of preventing the symptoms of poisoning. The importance of good food is equally great for both forms of poisoning—that caused by the therapeutic and that by the pro- fessional use of mercury. The general opinion of those who work with mercury in mirror manufactories appears to be, ac- cording to Kussmaul, that loss of appetite, and consequently diminished nutrition, favors very much the appearance of the severer symptoms, and, so far as therapeutic poisoning is con- ANTIMONY. 619 cerned, the most careful physicians consider loss of appetite in their patients to be the most positive contraindication against the energetic continuance of mercurial treatment. The same means are also of service when the symptoms of poisoning have already appeared. Since the elimination of the poison by the skin is generally established, the cause of the favorable action of warm baths is explained by the increase of the secretion of the perspiration. As a further means of hastening the elimination of mercury, the use of potassium iodide in large doses for a long time has been recommended as the result of very satisfactory experiments. These experiments, to be sure, are not entirely conclusive ; yet it must be acknowledged that the numerous and closely agreeing investigations upon the elimination of mercury in general, or its increase in the urine in cases of mercurial poisoning, after the administration of potassium iodide, render the employment of this drug advisable. For the treatment of the stomatitis the best means known is the most scrupulous cleanliness of the mouth. Electricity has for many years been recommended in the treatment of the mercurial tremor. CHAPTER VI. ANTIMONY-POISONING. Ackermann, Virchow's Archiv. Bd. S5.—Nobiling, Zeitschrift f. Biologie. Bd. IV— Saikowski, Virchow's Archiv. Bd. 34.—Buchheim und Eisenmenyer, Eckhard's Beitrage. Bd. V.—Kleimann und Simonowitsch, Archiv fiir Physiologie. Bd. V. In order to detect antimony in the organs and fluids the or- ganic matter must first be destroyed, preferably by hydrochloric acid and potassic chlorate. Of the compounds of antimony almost the only one to be con- sidered in toxicology is the familiar double tartrate of antimony and potassium, the so-called tartar emetic; in addition, however, a few cases are known of poisoning caused by the terchloride and the pentasulphide of antimony ("golden sulphide"). Cases 620 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. of poisoning by working with and using metallic antimony are said by van Hasselt to be frequent; yet in those cases where arsenic and other poisons are almost always present at the same time, it is very difficult to determine the part played by the anti- mony. The majority of the cases of poisoning by tartar emetic are caused by its medicinal use, but more frequently by the use of patent medicines which contain tartar emetic in large amounts. There are also occasionally cases of accidental poisoning by tartar emetic. On the whole, it is rarely used for criminal or suicidal purposes. From nine to fifteen grains is regarded as a fatal, or at least highly dangerous, dose for a healthy adult; van Hasselt gives as the fatal dose from two scruples to one drachm. Much larger doses, however, have been endured, and much smaller doses have been seen to produce very dangerous symptoms, as one-sixteenth and one-twenty-fourth of a grain (Taylor). In children, and in old or enfeebled persons, tartar emetic appears to act as an especially dangerous poison ; death has resulted in children from taking about three-quarters of a grain, and in adults, under favorable circumstances, from taking a little less than two grains. On the contrary, it has been taught for a long time and by the most eminent authorities, who, like Laennec, recommend the use of tartar emetic in acute inflammatory diseases, especially in pneumonia, that the system under such conditions "tolerates" the drug in otherwise incredibly large doses. As little as such a "tolerance" seems a priori credible, just so little has it been proved by sufficient experiment. The fact is, however, that not rarely enormous doses, an ounce and more, have been taken without fatal result; a fact which is not so difficult to under- stand, since the rapid production of vomiting and purging expels the largest part of the poison. Little is known with certainty concerning the existence of a chronic form of tartar emetic poisoning, unless we consider as chronic poisoning the more or less severe gastro-intestinal catarrh produced by repeated attempts at poisoning the same person by large doses, or the occasional continued use of the drug in small doses. The experiments of Mayerhofer and Nobi- ANTIMONY. 621 ling upon themselves teach us that such is the result of the long- continued use of small, so-called nauseating, doses; other than this these chronic forms of poisoning show little that is impor- tant. Clinical History of Acute Poisoning by Tartar Emetic The symptoms are those of the most severe gastro-enteritis. From a few minutes to one-half an hour or an hour after the poi- soning severe pain is felt in the mouth, throat, and along the oesophagus to- the stomach, and there is violent vomiting, and a little later purging. In all cases in which the action of tartar emetic is powerful, and consequently in cases of poisoning, col- lapse soon appears, forming a prominent feature, and increasing to the greatest extent. In many cases it appears when the symptoms of gastro - enteritis are wanting or only slightly marked (such as vomiting once or only a few times), and where diarrhoea is absent. Thus the case may resemble one of arsenic-poisoning, but in its farther progress it differs from the latter very materially. In fatal cases the deceptive remissions frequently seen in arsenic- poisoning are wanting, and recovery from tartar emetic poisoning is not rare, even when there is the greatest collapse with pulse- lessness, coldness of the extremities, etc. Convulsions are seen before death in fatal cases, and also occasionally in cases ending in recovery. One case, reported by Taylor (Mayer, Gleaves), is very peculiar; in this genuine tartar emetic pustules were said to have appeared in large numbers upon the skin on the third day after the poison was taken. Death may take place within twenty-four hours, but usually it does not result until after the lapse of weeks. It is not to be wondered at that severe chronic disturbances of the stomach are noticed as results of the poisoning. The post-mortem appearances seem to be very different in dif- ferent cases. The most important are those of gastritis, which are rarely wanting; in some cases this has reached the highest degree, and led to hemorrhagic exudation and infiltration upon and into the mucous membrane of the stomach, and even to 622 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. abundant hemorrhage into the intestinal canal. In several cases extension of the inflammation to the serous membrane has been reported. Slight ulceration of the mucous membrane has fre- quently been seen, and in some cases it has been found in the upper part of the small intestine. The reports, as to the presence of antimony in the organs of individuals who have been poisoned, differ very much ; it is cer- tain that antimony appears quickly in the urine after the inges- tion of small amounts of tartar emetic, and is eliminated with the urine in relatively large amounts. This elimination appears in some cases to be intermittent, as was mentioned above in the case of mercury. It frequently happens that none can be detected in the stomach even only a few hours after its ingestion, but at that time it always appears to be present in the liver, bile, and kid- neys. It has also been detected in the milk (Lehwald); so that poisoning of infants (nurslings) may take place. It has been found in the liver of the foetus when the mother had taken tartar emetic before delivery. It has also been found several times in the bones a long time (four months) after taking the poison. Of especial importance is the statement of Taylor, that he has found the antimony in the tissues in a form soluble simply in water. Theoretical and Experimental Considerations. Reference has already been made to the absorption and elimi- nation of tartar emetic. It should be added that large amounts of antimony have been detected in the vomited matters after the injection of the drug under the skin or into the veins. Hermann relies upon this fact not to commit himself to the statement that the vomiting produced by tartar emetic is independent of the local action of the drug upon the mucous membrane of the ali- mentary canal. Magendie observed that retching was produced by injection of tartar emetic into the veins of dogs after extirpa- tion of the stomach ; the supposition remains possible, however, that the drug was eliminated by the mucous membrane of the intestine, and exerted its local action; and in favor of this sup- position is the fact that as large doses are necessary to produce vomiting Avhen injected into the veins as when taken into the ANTIMONY. 623 stomach. These facts are not without value also for the inter- pretation of precisely the same conditions in arsenic-poisoning. It is not yet established whether all of the antimony elimi- nated into the intestine comes entirely from the bile or not. Whether and how far the collapse—the feeble action of the heart —which is a very prominent symptom, is caused by the gastro- enteritis, cannot be determined with certainty. There is no doubt that tartar emetic is a powerful cardiac poison; the cessation of the heart's action, which is observed in experiments, is at all events independent of the influence of the poison upon the cen- tral nervous system, since it takes place also after destruction of the medulla oblongata. Concerning the relation of the different constituents of this compound to its action, it is only known that the paralysis of the heart is in no way to be ascribed, as Nobiling thought, to the potassium which it contains, since tartrate of sodium and anti- mony acts with almost equal power, and the tartrate of antimony alone has a similar, though somewhat weaker, action. Anti- mony, therefore, appears to be the principal active ingredient. The action of tartar emetic upon the tissues is similar to that of arsenic; it produces violent inflammation when applied to the external skin as well as to the mucous membranes, but it is not a true corrosive, since it does not destroy the tissues by directly producing new chemical compounds, or by the extraction of water, or by simple solution. Among other experimental facts, we must notice that Sai- kowski has observed, after poisoning with antimonic acid, and to a still more marked degree after poisoning with the terchloride of antimony, the same changes in the glandular organs and in the muscular tissue of the heart, as those Avhich are seen after poisoning with phosphorus and arsenic. In many localities, it is said to be the custom to put gray antimony into the drinking- water of geese which are being fattened, in order to produce a very fat liver (Grohe and Mosler). A similar treatment of fowls is said to have been known centuries ago (Husemann). 624 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Treatment. As an antidote to tartar emetic drugs containing tannic acid should be given, preferably in the form of decoction; decoction of cinchona is frequently administered. The inflammatory ac- tion of the poison should be counteracted by surrounding it with albumen, milk, etc. In the more chronic form of poisoning, potassium iodide has been given, it having been assumed, from its analogy to poison- ing by mercury and other metals, that this drug favors the elim- ination of the poison. CHAPTER VII. RARER FORMS OF POISONING BY THE HEAVY METALS—IRON, MANGANESE, CHROMIUM, TIN, BISMUTH, GOLD, THALLIUM, AND OTHERS. Quincke, Archiv fiir Anatomie und Physiologie. 1868.—Pokrowski, Virchow's Ar- chiv. 22.— Piulet, Archives gener. 1833. — Linstow, Vierteljahrschrift fiir gerichtliche Medicin. 1874.—Mayencon und Bergeret, Canstatt's Jahresbericht. 1873.—Lebedeff, Canstatt's Jahresbericht. 1869.—SPfanowitsch, Ibid.—Marme, Gottinger Nachrichten. 1867. a. Poisoning by Salts of Iron is a very rare occurrence ; yet cases of criminal, suicidal, and accidental poisoning have occurred. The only preparations of iron which are poisonous are : ferrous sulphate, ferric chloride (in the form of the solution [and tincture]), and occasionally the tannate of iron in the form of ink. There are not a sufficient number of facts to enable us to fix the fatal or dangerous dose. Ferric chloride and ferrous sulphate appear to act with about the same severity; in fatal cases they were taken in doses of more than an ounce; yet, according to Orfila's experiments upon dogs, much smaller doses would suf- fice. iron. 625 We must, of course, separate the cases of true poisoning from those not rare cases, in which the medicinal use of some of the iron preparations has resulted in some disturbance of digestion, since otherwise we Avould be led to formulate a chronic form of iron-poisoning, and, in fact, these symptoms have occasionally been described as such. As an altogether doubtful curiosity, we find reported a case of iron-poisoning from the external application of the prepara- tion. This was the case of a boy who had worked with his hands in a solution of ferrous sulphate. After long-continued work of this kind, vomiting and purging came on as symptoms of the poisoning. The symptoms of poisoning by the above iron preparations are a toxic gastritis of slight intensity ; the matters vomited and, of course, the fseces are colored black, from the presence of the sulphide of iron. The post-mortem appearances are not characteristic; the greenish-black discoloration of the mucous membrane mentioned in some cases seems to have no connection with the poisoning. Theoretical and Experimental Considerations. The inflammatory action of the above salts of iron depends mainly upon simple corrosion. The ferric salts, and especially the chloride, coagulate albumen, and the same is true of the fer- rous salts also, but only because they are in part, in the body as well as in the air, quickly changed to ferric compounds. The iron preparations are eliminated with the urine; they exist in this fluid partly in the form of ferric and partly in the form of ferrous salts, no matter whether the former or the latter were ingested. The statement of van Hasselt, that the elimina- tion of iron, especially when it has been taken in small doses, does not begin for a long time, is very peculiar. Iron is said also to be eliminated AAdth the milk. Ferric salts injected into the blood act as an intense poison ; ferrous salts also are quickly oxidized, and produce coagulation of the blood, and consequently death from embolism. If injected very slowly in small amounts, only minute coagula are produced ; VOL. XVII.—40 626 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. these are taken up by the white blood-corpuscles, and distributed throughout all of the organs; if the organs are treated with sul- phide of ammonium, a green color (macro- and microscopic) is produced, which permits the detection of the presence of these iron-containing cells. Some of these salts of iron, such as the citrate, leave the organism in the urine unchanged. PokroAvsky found that the amount of urea in the urine of patients after taking iron was increased, and that there was a slight increase of the average temperature of the body. Unfortunately his experiments have not been repeated. b. Poisoning by Preparations of Manganese has practically no importance. The experiments of Laschke- witsch1 show that they differ very much from the iron salts. According to him they are very poisonous, and cause death by paralysis of the heart. c. Poisoning by Preparations of Chromium. Of these only chromic acid and its salts, the neutral chromate and bichromate of potassium, and the chromate of lead (chrome yellow), need be considered in reference to poisoning. Cases of acute poisoning by these preparations are chiefly accidental or suicidal, and are very rare ; chronic chromium- poisoning has been noticed in workers who handle solutions of the chromates or chromic acid, or who are exposed to the action of the dust from these compounds; those who are exposed to the action of the dust suffer from ulceration of the hands, which heals with difficulty, or of the mucous membrane of the nose, or of the scrotum, and other places. The chromate of lead has given rise to two cases of fatal poisoning in children who ate confectionery colored with it. The fatal dose of chromic acid and that of potassium bichro- mate appear to be the same, but that of the neutral potassium 1 Centralblatt fiir die medicinischen Wissenschaften. 1866. Vorlaufige Mittheilung. TIN. 627 chromate is larger, while that of the chromate of lead is very small. All of them produce death in doses of a few grains. The symptoms in the majority of cases are those of severe corro- sive gastro-enteritis, which is evidently caused by the escharotic properties of the preparation. 'It is remarkable that in a num- ber of the fatal cases the gastric and intestinal symptoms were almost completely wanting, and that the Post-mortem appearances in some cases consisted only of unimportant changes in the gastro-intestinal mucous membrane ; usually, however, ulceration or softening of the mucous mem- brane of the stomach was found. In some cases this change extended to the jejunum. d. Poisoning by Compounds of Tin is of the greatest rarity. Only two authentic cases are known. Frequently, poisoning of a mild grade is said to be caused by eating acid or fatty articles of food which have been kept in tin or tinned vessels, owing to the solution of the metal; it is to be remembered, however, that tin is very frequently contaminated with lead, copper, and arsenic, or that alloys of tin and lead are used instead of ostensibly pure tin. Thus the so-called rose tin (Bohemian tin) is said to contain as much as 10 per cent, of lead. The presence of arsenic in the tin is said to increase the action of the above kinds of food upon the metal. Stannous and stannic chlorides, which are used in the arts, produce very violent symptoms of poisoning. These symptoms are those of a toxic gastro-enteritis. In one case one-half a tea- spoonful of the substance proved fatal in three days, after very violent symptoms. At the autopsy the same appearances were seen as in corrosive sublimate poisoning. This substance does not act specially as a corrosive. Accord- ing to experiments upon animals (Orfila), it produces convulsions and also paralysis. Tin is eliminated with the urine. 628 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. e. Poisoning by Subnitrate of Bismuth. A few cases of so-called subnitrate of bismuth poisoning may be found in toxicological literature ; even fatal cases have been described. The doses used were from one to two and a half drachms. It is probable, however, that these were cases of arsenic-poisoning, since this is a very common impurity in the officinal preparation of bismuth. In some of the preparations the normal salt, which is much more soluble, and, therefore, much more dangerous, is said to ex- ist ; also free nitric acid, even in dangerous amount (Husemann). The existence of a chronic form of bismuth-poisoning is not established. According to Lebedeff, glycogen disappears from the liver of animals after long-continued feeding with bismuth. The ammo- nio-citrate of bismuth is said by Stefanowitsch to be a very powerful poison, and to act in a similar manner to phosphorus. f. Poisoning by Compounds of Gold. The terchloride of gold only requires mention; this is a powerful irritant and escharotic, like the nitrate of silver. In addition to this compound, the double chloride of sodium and gold, which produces the same effects, only in a less degree, has come into use again. Gold is eliminated with the urine, and is said to possess a constitutional action which is as yet undeter- mined. Formerly cases of poisoning have been ascribed to the therapeutic use of this and other preparations of gold. g. Poisoning by Thallium. This substance is, as it appears, a powerful poison both in the metallic form and in combination ; the carbonate is said to be fatal to dogs and rabbits in doses of fifteen grains when taken by the mouth, and to rabbits in doses of three quarters of a grain when given subcutaneously. It is, according to Marme and Rabuteau, a muscular and cardiac poison, and in its action re- sembles mercury in one respect and potassium in another. PHOSPHORUS. 629 I shall not treat of the compounds of platinum, palladium, osmium, iridium, rhodium, nickel, and cobalt, since they have not yet become important practically, nor has their physiological action been determined accurately. The perosmic acid may be mentioned as having recently attracted the attention of anato- mists. Its pungent fumes, like those of iodine, bromine, etc., are very irritating to the mucous membrane of the air-passages ; taken internally it is only dangerous in large doses, such as thirty grains and more. Vulpian and Raymond' have described one case of osmic acid poisoning in a factory employee. CHAPTER VIII. PHOSPHORUS-POISONING. t>. Hauff, Wurtemberg. Correspondenzblatt fiir Aerzte. 1860.—Lewin, Virchow's Archiv. Bd. XXI.— Wagner, Archiv f. Heilkunde. 1862.—Mannkopff, Wiener medicinische Wochenschrift. 1863.—Ehrle, Cliarakteristik d. acuten Phosphor- vergiftung. Tiibinger Inauguraldissertation. 1861. und Deutsche Klinik. 1861. —Bauer, Zeitschrift fiir Biologie. Bd. VII.—Eulenburg und Landois, D. Ar- chiv f. klinische Medicin. Bd. III.—Juergensen, Berl. klin. Wochenschrift. 1871. —Nobiling, Bayr. arztl. Intelligenzblatt.—Herrmann und Brunner, Pflueger's Archiv. Bd. III.—Menard, Etudes experiment, etc. These, Strassbourg. 1869.— Knoevenagel (Traube), Berliner klin. Wochenschrift. 1869.—Ebstein, Archiv d. Heilkunde. 1867 u. 1868.— Bellini, Lo Sperimentale. 1867.—Lebert et Wyss, Archives gene>. 1868. — Cunier et Vigier, Bull, gener. therapeut. 1868.—Ran- vier, Gazette mGdic. de Paris.—Alter ( Wyss), Experimentelle Beitrage u. s. w. Inauguraldissert. Breslau. 1867.—Bernhardt, Virch. Archiv. Bd. XXXIX— Hartmann (Buchheim), Zur acuten Phosphorvergiftung. Dorpat. 1866.—Munk und Leyden, D. acute Phosphorvergiftung. Berlin. 1865.—Th. Husemann und Marme, Nachrichten d. Geselischaft u. s. w. zu Gottingen. 1866.—Dybkowski, Hoppe-Seyler medic, chem. Untersuchungen. Heft. 1.— Bamberger, Wiirzburg. medic. Zeitschrift. Bd. VII—Gunning, Tjidschrift vor Geneeskunde. 1866. (Canstatt Jahresbericht.)—Klebs, Virchow's Archiv. Bd. 33.— Wyss, Schweizer- ische Zeitschrift. 1864.—Schultzen und Riess, CharitS-Annalen. Bd. 15.— Tuen- gel, Klin. Mittheilung aus dem allg. Krankenhause in Hamburg. 1863. und Vir- chow's Archiv. Bd. XXX.— Vohl, Berl. klin. Wochenschrift. 1865.—Schultzen, Zeitschrift fur Chemie v. Beilstein. 1867.—Koehler, Ueber Werth und Bedeu- 1 Gazette med. de Paris. 1874. 630 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. tung des sauerstoffhaltigen Terpenthinol u. s. w. Halle. 1872.—Personne Comptes rend. 1869. und Bull, gener. therapeut. 1869.—Andant, Bull, gener. therap. 1868.—Perls, Medic. Centralblatt. 1873.— Wegener, Virchow's Archiv. Bd. XL.—Bibra und Geist, Die Krankheiten u. s. w. Erlangen. 1847. Of phosphorus and its compounds as sources of poisoning, the former only requires notice. Phosphide of zinc has been observed to act in a similar manner. In addition to these, phos- phuretted hydrogen is the only compound which has an impor- tant poisonous action, which is, however, very different from that of phosphorus, and has never, as it appears, caused poisoning in man. Phosphoric acid, with the exception of a slight irritant effect, has no poisonous action, and the same is true of phos- phorous acid. These are practically unimportant. Of the allotropic modifications of phosphorus only the so- called white phosphorus is poisonous; the red (amorphous) variety is perfectly harmless, even in very large doses. The detection of white phosphorus is best accomplished by the combined methods of Mitscherlich and Lipowitz. The sus- pected fluids or tissues, finely divided and treated with water, are placed in a flask connected with an upright glass condenser, and heated over a water-bath in a dark room ; if phosphorus is present, luminous vapors will appear in the lower part of the condenser. For further demonstration it is best to introduce into the fluid a few pieces of sulphur (melted on a thread), and first heat out of contact with the air, by closing the condenser; after twenty or thirty minutes the pieces of sulphur on the thread are removed and the condenser opened, when the phos- phorescence can be seen upon the entrance of atmospheric air. If phosphorus was present, a part of it has been precipitated on the pieces of sulphur, and these can be used for other tests. Phosphorus-poisoning shows itself in two distinct forms, which are sharply defined clinically and in the main anatomic- ally. These are : Acute poisoning, which has almost invariably been produced by taking phosphorus internally, and chronic, which is caused by the inhalation of phosphorus vapors. PHOSPHORUS. 631 1. Acute Phosphorus-Poisoning. Phosphorus may be swallowed in five forms: in that of matches, phosphorus pastes (rat poison), more rarely as phos- phorus oil, phosphoric ether, and as pure phosphorus. In by far the majority of cases, even with suicidal intent, it is taken in the form of matches. The frequency with which this is used for suicidal purposes has increased enormously during the last ten years, although recently its use appears to be decreasing some- what. Hundreds of cases can easily be found in literature. Matches are also the frequent source of criminal poisoning, and in children only of accidental poisoning. Phosphorus pastes have frequently been used with criminal and suicidal intent, and have also been taken accidentally. Pure phosphorus, phospho- rus oil, and phosphoric ether are difficult for the laity to obtain ; these are often the cause of medicinal poisoning. In England a patent medicine for the treatment of worms was found to con- tain a large amount of phosphorus. This preparation gave rise to one fatal case of poisoning. The local action of the phosphorus upon the stomach is mate- rially less when it is taken in large pieces than when in a finely divided state. The so-called fire-eaters are said to swalloAv Avhole sticks of phosphorus, weighing fifteen grains and more, without injury. Van Hasselt doubts this statement; in favor of it, how. ever, is the fact that, in animals, very large pieces pass from the intestine almost unchanged, and have but slight action. When ever phosphorus has produced severe poisoning, it has almost always been used in a finely divided state or dissolved (in oil or ether). In such a condition it is a very active poison ; for an adult, one grain should be designated as a dangerous or fatal dose ; for children, a small fraction is sufficient. The amount of phosphorus in matches varies exceedingly (according to Gun- ning, from one-fifth to one grain in one hundred match-heads). Moreover, their action varies according as the heads are swal- loAved Avhole, or an extract or emulsion prepared with water, al- cohol, or some fatty fluid, like milk, which dissolves phosphorus more easily, is taken ; notice should also be taken of the manner 632 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. in which the phosphorus paste is applied to the match ; whether, for example, the head is soaked or coated with a varnish Avhich is difficultly soluble in water or not. An important factor in determining this is the rapid appearance or absence of vomiting. Thus it can be easily understood that in one case severe poi- soning has been observed after taking 35 or 40, and even after taking 8 matches (in a child two years old), while in another even 400 matches did not prove fatal. The amount of phos- phorus in pastes used for poisoning rats varies greatly, accord- ing as the paste is freshly prepared or not. The case of Harting, in which the ingestion of a single match is said to have produced severe poisoning, is open to considerable doubt. It may be stated here that no authentic case is known in which poisoning has been caused by the burning of matches ; the experiments performed by van Hasselt and Pappenheim to set- tle this question, so often discussed by the laity, gave only nega- tive results. Non-susceptibility to the action of this poison, acquired by habitual use, or so-called idiosyncrasy, does not exist; most animals, also, are affected by it to about the same extent as man ; parrots only are said to enjoy immunity. Symptoms. The first symptoms of poisoning are usually gastric: pain in the epigastrium and vomiting ; the latter is usually not violent, occurring but once, or only a few times. Generally it comes on in the course of the first twenty-four hours, frequently soon after the ingestion of the poison. The vomited matters, except when they contain phosphorus, show nothing special. When phos- phorus is present they are luminous in the dark. Discharge of luminous masses per anum has been observed; occasionally, when much phosphorus has been taken, a luminosity of the breath has been noticed soon after the ingestion, but it is proba- ble that in these cases the luminous gas came from the mouth or stomach, and not from the lungs. Frequently the peculiar odor of phosphorus is perceptible in the breath. Other symptoms do not necessarily follow the vomiting, if the stomach has been com- pnospnoRus. 633 pletely emptied, or if the dose has been small. Almost always, however, there comes on a comparatively healthy condition, which may last two or three days, or even longer. Then the severe symptoms begin usually with jaundice, which increases more or less rapidly until it reaches the highest degree of inten- sity ; with this comes urticaria, which generally accompanies severe jaundice. Simultaneously with the icterus there is more or less pain in the epigastrium, especially in the region of the liver. At this time enlargement of the liver can usually be de- tected by palpation and percussion, and this organ continues to increase while the patient is under observation ; mild febrile dis- turbances are frequent, and vomiting, now more or less bloody, comes on again. With the appearance of these symptoms there is very great disturbance of the general condition, and soon alarming weakness of the heart's action is noticeable. The pulse varies greatly in frequency (in one case the number of pulsations was diminished to 40), being much accelerated, extremely feeble and small toward death ; the heart-sounds are feeble, and are early characterized by the failure of any difference between the first and second sounds (fcetal heart-sounds—Stokes); finally, the first sound disappears entirely. At the height of the disease there is frequently a tendency to hemorrhage of various kinds ; the vomiting of blood above men- tioned may be very copious, and with it there may be bloody stools ; also bleeding at the nose, metrorrhagia, and often prema- ture appearance of the menses. The hemorrhage into the skin and subcutaneous cellular tissue shows itself in the form of pete- chia and extensive ecchymoses. The hemorrhage from a simple leech bite or from cupping cannot be stopped. The intellect sometimes remains entirely intact; profound stupor is a bad symptom ; it precedes death by not more than twenty-four hours. The failure of the intellect may show itself in different ways: as simple coma, as coma AA'ith restlessness, and in some cases as violent, noisy delirium. Convulsions are not rare as death approaches. The temperature of the body remains about normal until the approach of death. Then, for the first time, there is a lowering of the temperature, or in some cases a considerable increase. 634 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Of especial interest is the character of the urine eliminated. At first there is no marked change in amount or density; later it is diminished in amount, during the last few days even to the minimum (between three and four ounces). It usually contains a small, rarely a large, amount of albumen, frequently blood and so-called fibrinous casts, and, with the appearance of jaundice, biliary pigments and acids. Leucin and tyrosin are rarely found in it, but paralactic acid is often detected in large amount, especi- ally in fatal cases. Schultzen and Riess found that the urea almost completely disappeared upon the approach of death; and in its stead there appeared, even in cases ending in recovery, a peculiar nitrogenous "extractive" material, which was, accord ing to these authors, very similar to peptone. In experiments upon animals, this disappearance of urea could not be produced. Death may take place unexpectedly at any time, even before the appearance of the most unfavorable symptoms, and fre- quently toward the end of the first Aveek, or sometimes in the sec- ond Aveek. Slightly marked gastric symptoms by no means authorize the prediction of a mild course of the poisoning. In cases of recovery from severe poisoning, the disease may drag along for a long time. In the cases of this kind observed by Schultzen and others, the swelling of the liver did not disappear for more than four weeks; the jaundice disappeared, albumen could no longer be detected in the urine, and the repeated and copious intestinal hemorrhage ceased. A very different form of poisoning from that above described is one in which the progress is very rapid; this occurs in very acute poisoning. In one case death took place in less than nine hours, and cases which have proved fatal in two or three days are not rare. In such cases all of the symptoms develop much more quickly. The vomiting which first appears may be fol- lowed immediately by the most severe symptoms. Jaundice is only absent in those cases which run a very rapid course; in one case (Drachmann), however, it did not appear, although death did not take place until the fourth day. In a very few cases an apparent diminution in the size of the liver, which was previously enlarged, has been observed a few days before death. PHOSPHORUS. 635 Post-mortem Appearances. The great interest which phosphorus-poisoning has won for pathology, during the last decade, depends in great measure upon the pathological appearances to which it leads. In this connec- tion v. Hauff has performed the greatest service, by teaching that fatty degeneration of the liver is a usual result of this form of poisoning. After death there is found, almost without excep- tion, a more or less intense yellow coloration of the skin and conjunctivae (compare that which relates to icterus under " Symp- toms"). Ecchymoses or petechise are also frequently seen. The muscular tissue is usually yellowish-red and fatty. On opening the abdomen, the familiar garlicky odor of substances contain- ing phosphorus is perceived. The blood is only partly coagu- lated. Ecchymoses are seen beneath the pericardium and endo- cardium. The muscular tissue of the heart is pale, and evenly colored of a light grayish-yellow, or in some cases (especially apparent beneath the endocardium) it is striped or contains net- like tracings formed by light wavy lines upon a grayish-red ground ; the cardiac tissue is brittle, and appears fatty both to the touch and to the eye; in short, we see a typical fatty heart. The lungs show nothing abnormal, except the hypostatic con- gestion, and the pleural and bronchial ecchymoses. The liver is, as a rule, enormously enlarged, and presents the appearance of one in a high degree of fatty degeneration ; it is usually pale- yellow, but may be deep-yellow ; the acini are plainly perceptible and large. The substance is brittle and fatty; here and there ecchymoses beneath the capsule or along the course of the blood- vessels may be seen. The spleen is often recently enlarged. The gastric mucous membrane is swollen, grayish, and non-transpa- rent, with small or large ecchymotic spots, and rarely ulcers, which are small and in the pyloric region. The mucous mem- brane of the duodenum often presents the same appearances. That of the small and large intestine is pale, with occasional ecchymoses. The contents of the stomach and intestine are often bloody ; the intestine contains but little or no bile, and the gall- bladder but little of a biliary or rather mucous fluid. The kid- neys are very much enlarged and fatty. 636 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. In the central nervous system there are no important changes. In a few cases, in which the duration of the disease was only a few hours, the autopsy gave almost completely negative results. Sometimes important changes occur only in the liver. In many cases this organ is scarcely enlarged, and may be even dimin- ished in size. It no longer has so pale a yelloAV color, but is, on the whole, more of a dark-red; its consistency is tougher; the lobules are small and wasted. In this dark-red tissue may be seen occasionally insulated spots of varying size, which have the ordinary appearance of phosphorus - poisoning, and are of a strongly-marked yellow color. Under such circumstances the appearance of the liver gives the impression that the fatty de- generation, which in the yellow patches is still in its prime, has in the red portions advanced to the stage of atrophy. Microscopic examination shows, as the cause of the fatty appearance of the organs, that the muscular fibres of the heart and muscles of the body, the hepatic and renal epithelial cells, and the cells of the gastric glands, are filled with large or small fat drops. Klebs found also fatty degeneration of the smaller blood-vessels and capillaries, to which he attributes the hemor- rhages. The reports and opinions of authors differ in regard to the appearances in the liver. Some of the authorities, at the head of whom stands Mannkopf, found, especially in those cases with commencing atrophy, proliferation of cells in the interstitial tis- sue, an increase of this tissue, and aggregations of nuclei; others, among whom are Schultzen and Riess, never have seen such an active process in the interstitial tissue, but simply a fatty degen- eration of the cells. This difference in the microscopic results has importance in connection with the controversy as to whether the changes taking place in the liver in phosphorus-poisoning are essentially different from those in acute yellow atrophy of the liver or not. The experiments of Wegener are conclusive so far as the ana- tomical side of the question is concerned. Wegener found "an interstitial hepatitis of the most marked degree. The result of this, when produced by the use of relatively large doses of phosphorus continued for several months (that is, in comparison with the doses used by Weo-e- PHOSPHORUS. 637 ner to produce a modification of the growth of bone, such as, for example, 0.0015 gramme (one-fiftieth of a grain) in rabbits, is always essentially the same, namely, an atrophy of three kinds: smooth induration of the organ, or a form of atrophy occasionally seen in man as the result of syphilis, a hepar lobatum with numerous deep contractions which produce a great deformity of the organ, or, finally, the typical granular atrophy, the classical cirrhosis of the liver. In all of these cases chronic icterus is present. If the atrophy is of the last-mentioned variety, there are found those regularly developed secondary affections, which are familiar in human pathology, viz., venous hyperaemia of the stomach and intestines, indurative enlargement of the spleen," etc. This complete description leaves no doubt about the fact that in cases of chronic poisoning by phosphorus the most exquisite proliferation of cells takes place in the interstitial tissue of the liver ; this gives, therefore, the most important evidence in favor of the views of those who, with Mannkopf, consider the changes which take place in the liver in acute phosphorus-poisoning and acute atrophy of the liver as identical. The chemical side of this question must be considered later in the theoretical part. In cases of very acute poisoning, in which the post-mortem examination has not been postponed too long, phosphorus can frequently be detected in the contents of the stomach and intes- tines by its luminosity in the dark, or by means of Mitscherlich's apparatus ; in other cases the detection of phosphorous acid ren- ders it at least probable (Sonnenschein) that white phosphorus was present. Tuengel, by means of Mitscherlich's process, detected phos- phorus in the liver of a girl who died nine hours after swallow- ing matches, the autopsy having been performed forty hours after death. On the contrary, in one case, in which death took place within twenty-four hours after the poisoning, phosphorus could not be detected in any organ. Theoretical and Experimental Considerations. Of the theoretical questions bearing on acute phosphorus-poi- soning the one most discussed is, whether the disease is due to the direct action of the phosphorus on the metamorphosis of tis- 638 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. sue, or to that of some compound of phosphorus formed within the system. Phosphorous and phosphoric acids may exist in the body as the result of the oxidation of the poison ; the facts which lead to the assumption that these compounds are products of intermedi- ate steps in its action are not conclusive. Moreover, the injuri- ous action of these compounds is far too slight in proportion to the poAverful action of free phosphorus. One of the principal reasons given by some of the investiga- tors of the present day for considering that phosphorus could not act as such in the blood and tissues was its supposed insolu- bility in water, in the stomach, and in the blood. Phosphorus is, however, as Buchheim and Hartmann have demonstrated, soluble in water at a temperature of from 96.8° to 104° Fahr., in the proportion of 0.022 per cent.; but in the or- ganic fluids, such as the bile, it is somewhat more soluble. It is also true that phosphorus, when taken into the body—especially into the stomach—either in solution or undissolved, goes into the blood. This has been proved both in cases of poisoning in man, and experimentally by poisoning animals. Luminosity of the breath has been observed in animals when the phosphorus has been introduced into the stomach through the oesophagus, after cesophagotomy had been performed and the oesophagus tied above the wound. In one case, after exposure to phosphorus vapor, Vauquelin observed distinct luminosity of the urine. The objections, therefore, against the supposition of a direct influence of the phosphorus upon tissue-metamorphosis are un- tenable. A second question still undecided is, In what way is this ac- tion of phosphorus to be regarded? It has been thought that the phosphorus, or phosphuretted hydrogen formed from it, acts simply as a deoxidizer, but the poisonous doses are much too small to accomplish this. Schultzen almost always found paralactic acid in the urine in fatal cases of phosphorus-poisoning. Schultzen and Riess found, in^ the earlier stages of poisoning,* a peptone-like substance ; Wyss found leucin and tyrosin; Schultzen and Riess detected tyrosin in the blood of dogs poisoned with phosphorus. These PHOSPHORUS. 639 authors saw the urea — the principal product of normal tissue- metamorphosis—almost entirely disappear from the urine in fatal cases. Since it has been well established that lactic acid is, under normal conditions, oxidized, the view of Schultzen and Riess, that the presence of phosphorus in the organism interferes with the process of oxidation, is probably correct. The appearance of leucin and tyrosin and all of the other intermediate products of metamorphosis (the so-called peptones) in the urine corresponds entirely with this view. How this action is to be explained is completely unknown. In this, as in all other cases, the almost constant appearance of jaundice depends upon the reabsorption of the bile ; the simul- taneous presence of a large amount of the biliary acids in the urine proves this, as in many such cases of icterus an obstruc- tion to the flow of bile cannot be detected. The hemorrhages appear to depend upon the fatty degenera- tion of the walls of the smaller blood-vessels. The symptoms of gastro-enteritis depend, in small part only, upon the local irritation ; perhaps the products of the oxidation of the phosphorus (phosphorous and phosphoric acids) may take part in this action; in general, these symptoms, especially so far as they belong to the later periods, are consequences of the gen- eral action. The constant changes in the mucous membrane of the stomach, the gastro-adenitis of Virchow, are of the same na- ture as the changes in the liver, muscles, and kidneys ; these are found also after the injection of phosphorus oil into the rectum. Whether the fatty condition of all of these organs is to be re- garded as a simple fatty infiltration—that is, a deposition of fat OAving to its non-consumption—is not decided. The considerable increase of fat in the blood appears to favor this view (Melm). Menu found three per cent, of fat in the blood of dogs poisoned with phosphorus, against two per cent, under normal conditions. Bamberger, on the contrary, found no increase of fat in the blood. The fact that in the liver, where this fatty condition is most marked, genuine inflammatory (interstitial) changes may exist somewhat contradicts this view. Perls has, as it seems, given the proper definition to distin- guish between fatty infiltration and fatty degeneration. If, in a 640 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. tissue, fat is stored up, and there is a diminution in the amount of water and a corresponding increase of the non-volatile con- stituents, this may be considered as a fatty infiltration. Fatty degeneration exists where, with a tolerably constant amount of water, the fat takes the place of other non-volatile substances. In the livers of two dogs poisoned with phosphorus I found: At a temperature of 212"1 Fahr. ... ( 25.78 of dried substance. 12.5 of fat. In 100 grammes of liver, j 24 g u u 8.0 " In dogs, under normal conditions, I found that the amount of water never exceeded 75 per cent.; the above figures, there- fore, show that the fatty condition of the liver, at any rate, in phosphorus-poisoning, is due to fatty degeneration. Bauer's estimations of fat in the livers of dogs poisoned with phosphorus and his conclusions from other considerations, agree with this. Practically, as well as scientifically, the question as to the identity of the changes in acute phosphorus-poisoning and acute atrophy of the liver, is interesting. The anatomical side of the question has been already treated in speaking of the post-mortem appearances ; the changes in tissue-metamorphosis, however, in no way appear to be the same in the two cases. The most im- portant labors of Schultzen and Riess in regard to the chemistry of these changes lead to the conclusion that the very frequent ap- pearance of sarkolactic acid in the urine is characteristic of the changes in tissue-metamorphosis in phosphorus-poisoning. Since this substance has thus far never been found in acute atrophy of the liver, we may accept this conclusion. Less characteristic is the appearance of leucin and tyrosin in acute atrophy of the liver, since these substances have been repeatedly detected in the urine in phosphorus-poisoning, although in much smaller amounts than in acute atrophy of the liver (Wyss). Finally, although no more essential differences can be estab- lished in the processes taking place in acute atrophy of the liver and acute phosphorus-poisoning, yet it cannot be concluded that idiopathic acute atrophy of the liver does not exist, and that in doubtful cases phosphorus-poisoning must be inferred. This PHOSPHORUS. 641 unwarranted conclusion would lead to very dangerous conse- quences, especially in medico-legal practice. Treatment of Phosphorus-Poisoning. This must aim exclusively to render the poison harmless before its absorption into the blood. This is best accomplished, if the patient is seen early enough—that is, at the latest within the first twenty-four hours,—by the administration of emetics, or better still by the use of the stomach-pump in combination with active cathartics. The physician can always do this, if he has an oesophageal sound. Bamberger considers sulphate of copper to be the best emetic. By the use of this drug we succeed in producing, in addition to the act of vomiting, an at least tempo- rary harmlessness of the poison ingested. The copper salt forms with the phosphorus a compound which is very slightly soluble, so that the pieces of phosphorus in the stomach (heads of matches, etc.) are surrounded with a coating of the slightly soluble phosphide of copper. Recently oil of turpentine has been recommended as an ener- getic antidote in acute phosphorus-poisoning. The use of oil of turpentine in chronic phosphorus-poisoning (by the vapor) is old ; it is based upon the fact that the vapor of phosphorus is not luminous in an atmosphere strongly impreg- nated with turpentine. Andant introduced the use of turpen- tine into the treatment of acute phosphorus-poisoning. Accord- ing to Koehler, no action takes place except with the unrectified oil of turpentine. The greatest scepticism should be placed against the Avide-spread enthusiasm of some advocates of this treatment, as Bamberger has already indicated. We must insist that, notwithstanding the numerous records concerning this so- called antidote, it is not proved that its action is absolutely cer- tain. The cases observed are not sufficiently conclusive, and the results of experiments are not entirely in harmony. Moreover, the antidote acts with certainty only when the amount of phos- phorus taken does not much exceed the ordinary fatal dose; it is without effect when the dose is very large. But the action of a dose ordinarily fatal is often uncertain when no antidote is VOL. XVII.—41 642 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. given, the effect frequently being much less than would be ex- pected. It is not, therefore, just to assert that the timely administra- tion (within twenty-four hours) of oil of turpentine renders it unnecessary to remove the poison by evacuating the stomach. The latter is by far the more important. Nevertheless, turpen- tine is doubtless to be recommended, and can be borne in doses of thirty minims and more every fifteen minutes until a total of tAvo fluid drachms and a half and upwards is reached. The antidotes formerly recommended have not stood the test. The same is true of the administration of albumen, etc., to envel- op the poison. All fatty substances, and also the yolk of eggs, are to be studiously avoided on account.of the ready solubility of phosphorus in fat. Transfusion has naturally been recom- mended by Eulenburg and Landois in acute phosphorus-poison- ing, but satisfactory experiments as to its results have not been reported. It is out of place here to treat of the rules which have been or should be adopted by boards of health to diminish the occur- rence of phosphorus-poisoning. These could refer only to phos- phorus pastes so frequently used for poisoning rats, and to matches. The pastes seem to possess such advantages for the destruction of these pests, that it is difficult to do without them. In the manufacture of matches, the aim appears to have been, almost from the beginning, to replace the dangerous white phos- phorus by the innocuous red variety. When the so-called Swe- dish matches, which contain no phosphorus, shall come into gene- ral use, an absolute prohibition from employing the latter in the manufacture of the inflammable part of matches may be seriously considered. This Avould at the same time do aAvay with the most important source of chronic phosphorus-poisoning. 2. Chronic Phosphorus-Poisoning. Of the forms of chronic poisoning, that caused by the inhala- tion of phosphorus vapor is the only one which has been estab- lished Avith certainty and is well recognized. Such cases seem to occur very rarely in the phosphorus factories ; but they are, PHOSPHORUS. 643 on the contrary, frequently observed in workers in match factories. Those workmen Avho are engaged in dipping the wood into the phosphorus mass, and those employed in the drying-rooms are the principal ones who are liable to be poisoned. This form has also been observed in the so-called phosphorus bronze factories. As symptoms of chronic phosphorus-poisoning are mentioned : chronic bronchial catarrh, accompanied by chronic gastro- enteritis, loss of appetite, and usually constipation. The most important and only specific result of the poisoning is the familiar disease of the lower jaw, called phosphorus necrosis. This develops in from six months to many years after the workman has commenced the dangerous employment; occasion- ally the first symptoms are not observed until after the patient has ceased working with phosphorus. The disease occurs in the lower jaw most frequently and most severely; in the upper jaw rarely and in a milder form. Yet the most extensive ne- crosis of the upper jaw has been observed; even cases are known in which the disease has extended to the cranial bones, and death from meningitis has followed. The disease almost ahvays begins in carious teeth or gaps between the teeth, and almost never exists in persons with sound teeth. It develops into and runs the course of a chronic peri- ostitis, and leads to extensive necrosis of the lower jaAv. In the milder cases the disease is limited to the alveolar process; then, after the spontaneous expulsion or the extraction of the necrosed portions, recovery takes place; in the severe cases necrosis of the greater part or the whole of the jaw results, yet recovery may ensue even in these cases. The occurrence of abundant osteophyte formations on the affected bones has long been recognized as the anatomical pecu- liarity of the disease. The frequency of similar diseases seems to have diminished considerably in recent times. Sufficient ventilation is the most important precaution for the protection of the workmen; in many factories only workmen Avith perfectly sound teeth are employed. The treatise of Wegener is absolutely necessary for the thor- ough understanding of this subject. 644 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Wegener showed that it is easy to produce in animals the peculiar periostitis of the lower jaAv, which leads to necrosis, by exposing them for several weeks to the action of phosphorus vapor. This evidently acts as a local irritant upon the perios- teum, acting more readily in those cases where opportunity is given for the attack of the vapor by decayed or previously wounded teeth. Wegener showed also that phosphorus taken in the form of vapor by inhalation or internally, in the smallest doses, acts "as a specific formative excitant to the osteogenic tissue," and under otherwise normal conditions leads to a considerably increased development of the compact tissue in the long bones. These results are shown most plainly in young animals while still growing ; in them it happens that not rarely all of the spongy tissue is crowded out and its place filled with compact tissue. Wegener has succeeded in producing in hens a complete closure of the medullary cavity by compact bone tissue. CHAPTER IX. POISONING BY ARSENIC AND ARSENIURETTED HYDROGEN. Fleck, Archiv fiir Biologie. Bd. VIII. — Bjehm und Johannsohn, Arch, fiir experi- mentelle Pathologie. Bd. II,—Lehmann, Het-Arsenikzuur. u. s. w. Dissertat. Amsterdam, 1773.—Cunze, Henle und Pfeufer's Zeitschrift. III. Bd. 28.— Schaper, Beitrage zur Arsenikvergiftung. Berlin, 1846.—Diskussion zwischen Schaper und Pfeufer in Henle-Pfeufer Zeitschrift. I. Bd. 6. — Schmidt und Stuerzwage, Moleschott Untersuchungen. Bd. VI.—Boehm und Schaefer, Wiirz- burger Verhandlungen. N. F. III.—Saikowski, Virchow's Archiv. Bd. XXXIV. —Schaefer, Sitzungsber. der Wiener Akademie. Math, naturwissenschaftl. Classe. Bd. 41.— Virchow, Dessen Archiv. L\ll.—Sklarek, Reichert u. Dubois Archiv. 1866.—Grohe u. Mosler, Virchow's Archiv. Bd. XXXIV—Mueller, Wiener medic. Wochenschrift. 1866. Arseniuretted Hydrogen:— Vogel, in Neubauer und Vogel's Anleitung u. s. w. Wiesbaden, 1863.— Naunyn, Reichert und Dubois Archiv. 1868.—Eulenberg, Die schadlichen u. s. w. Gase. The detection of arsenic in the animal fluids and tissues is only possible, as in the case of the other poisonous metals, after ARSENIC. 645 previous destruction of the organic matter by hydrochloric acid and potassic chlorate ; incineration of the substances to be anal- yzed is not permissible, since the terchloride of arsenic, which is formed by compounds of arsenic in the presence of the alkaline chlorides, is quite volatile. For the same reason also the de- struction of the organic matter with hydrochloric acid and potassic chlorate must be performed over a water-bath. From the solution thus obtained the arsenic is precipitated in the form of sulphide, and this compound, after purification and, as a rule, conversion into arsenic acid, is used for obtaining the character- istic reactions. The best process for finally determining whether a suspected substance is or contains an arsenical compound is that of Marsh. When articles which may serve as the source of poisoning, such as wall-paper, colored clothing, food, etc., are to be tested for arsenic, Marsh's test can be performed directly with the sus- pected material. In the examination of articles of food and also of vomited matters in cases of suspected poisoning, it is well to remember that the arsenic is usually emploj^ed in the form of arsenious oxide. This is mixed with the substance usually only in a coarsely powdered state, and is, moreover, soluble with dif- ficulty ; on this account, and also on account of its high specific gravity, it is frequently possible, after allowing the mixture to settle, carefully decanting and washing the sediment, to find at the bottom of the vessel particles.of the arsenious oxide, with Avhich the arsenic mirror can be obtained immediately by Marsh's test or by reduction with charcoal. The quantitative estimation is made by obtaining the ammo- nio-magnesian arseniate in a pure form. A very complete de- scription of all the methods and manipulations used in the detection of arsenic may be found in Otto's Anleitung zur Aus- mittelung der Gif te, Braunschweig, 1856. Acute and chronic arsenic poisoning are totally different in nature and importance. Acute poisoning by arsenic has been and is at the present time by far the most frequent cause of death by poisoning.. In the different European countries, at the present time, more than three-fourths of all the cases of poisoning or attempted poison- 646 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. ing which have been investigated legally are due to the com- pounds of arsenic. The inventor of the famous aqua toffana (which according to Garelli was nothing more than a solution of arsenious acid in aqua Cymbalarire) confessed that he knew of 600 cases of fatal poisoning caused by this preparation alone. Of the compounds of arsenic, arsenious oxide (so-called white arsenic) is almost exclusively used. The other compounds have but little importance. According to the latest investigations of Schroff upon this subject, metallic arsenic, whose poisonous prop- erties were formerly denied by C. Schmidt, is almost as active as arsenious acid. At all events, the so-called fly-poAvder, which is a frequent source of accidental and criminal poisoning, and which consists chiefly of metallic arsenic, is by no means harm- less. This may, however, act by virtue of the arsenious oxide, which is always mixed with it in amounts varying from ten to thirty per cent. Arsenic oxide, which is almost as active as the arsenious, practically is not employed as a poison. The pure sulphides of arsenic are not poisonous, although the native sulphides found in commerce and also the artificial preparations (orpiment, King's yellow, realgar, etc.) always con- tain mechanically mixed with them considerable amounts, even to thirty per cent., of arsenic acid. The salts of arsenious and arsenic acids act, as a rule, more powerfully than the acids themselves, since the latter are much less soluble. Among the most important compounds of arsenic are the arsenical pigments, especially the so-called Schweinfurt green (a mixture of the arsenite and acetate of copper) and Scheele's green (arsenite of copper). The organic compounds of arsenic (kakodyl, for example) and arseniuretted hydrogen have a spe- cial pathological action which will be spoken of later. The methods by which the poison may get into the body are very different. The ingestion of arsenic in food or drink, with which it has been intentionally or accidentally mixed, may easily take place unnoticed even in very large amounts, since the vari- ous preparations in small quantities are tasteless; by far the largest number of cases of severe acute poisoning are caused in this way. Cases of acute poisoning have also been observed due ARSENIC. 647 to the illegal use of arsenical preparations (pigments) for color- ing playthings of children, who have sucked them. Rarely such cases occur due to the dust of arsenical colors, such as from the green tarlatan dresses which have been colored with Schweinfurt green. The external application of arsenious oxide or of orpi- ment even upon the normal skin for depilation has caused severe acute poisoning. The very frequent use, especially in patent medicines, of arsenical ointments and lotions for benign and malignant ulcers has resulted in several fatal cases of poisoning. The amount of arsenic which is sufficient to produce acute poisoning has been determined by many observations. Doses of less than one-sixth of a grain have produced injurious effects in adults. Evident symptoms of poisoning have been observed as the result of taking from one-fourth to one-half of a grain. In one case alarming symptoms were produced in a female by the continued use during four days of one-twenty-second of a grain daily. Such serious symptoms were produced in two men by taking a little less than two grains, dissolved in wine, that Taylor does not hesitate to ascribe an occasional fatal result to such a dose. The correctness of this vieAv is established by an observa- tion also made by him : a woman took half an ounce of Fowler's solution, which contains not quite two grains of arsenious oxide (as potassic arsenite), in unknoAvn doses during five days Avith a fatal result, and a strong servant-girl was killed by about two grains of arsenious oxide in two ounces of fly-water in thirty-six hours. The fatal dose does not seem to be very much smaller for children. On the other hand, cases are Avell known (leaving out of account entirely cases of arsenic-eaters, Avhich Avill be spoken of later) Avhich show that arsenic sometimes does not prove fatal, even in doses of more than from fifteen grains to tAvo ounces. Some of the conditions upon which the variation in intensity Avith which the poison acts in different cases are well known. It acts more severely when in solution than when undissolved ; hence, in general, the action of the very soluble alkaline arsenites is more powerful than that of a corresponding amount of the free acid. In this respect a distinction must also be made between 648 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. the two modifications in which arsenious oxide exists. The non- transparent variety is very slightly soluble in cold water, that is, in from 500 to 1,000 parts, and in 400 parts of boiling water; after boiling an hour it is, according to Taylor, soluble in forty parts ; by longer boiling with water the opaque variety is changed to the vitreous, of which boiling Avater dissolves about one part in ten. Moreover, the poison acts much more violently when taken upon an empty stomach. The so-called cumulative action does not exist, on account of its very speedy elimination with the urine. The experience of habitual arsenic-eaters goes to show that, in the case of this poison, habit affords a tolerably good protection against its action. Symptoms of Acute Arsenic-Poisoning. The symptoms appear much more quickly after large doses and when taken in solution. They rarely come on later than one hour after the ingestion, but in exceptional cases they may be delayed for six or eight hours. As a rule, the statement, fre- quently made, that there is a special taste upon the ingestion of the poison or as a beginning of the poisoning, is erroneous ; the taste is usually completely absent or is unimportant. The first symptoms, whether the arsenic is taken internally or applied externally, are those of a very violent gastro-enteritis, which frequently from the beginning runs a course resembling that of cholera: violent vomiting and purging, the discharges often resembling rice water, although sometimes they are bloody ; the vomited matters are sometimes colored greenish from admixture with bile. The laAv in many places orders that arsenic before it is sold shall be mixed with coloring matters, such as charcoal or indigo, which will impart their color to the vomit. Usually there is violent pain in the abdomen. Collapse of dangerous intensity appears very quickly, and- consciousness is usually retained till death. In other cases coma and convulsions appear in a longer or shorter time before death. Trismus has also been reported. The progress of acute arsenic-poisoning is, however, liable to many variations. In the first place, it may be influenced by the ARSENIC. 649 mode of application, as, for example, by the cutaneous eruptions Avhen applied to the skin. Yet cases occasionally occur Avhich run an entirely abnormal course, as, for example, cases in Avhich the gastric symptoms are entirely wanting or but slightly marked, while collapse, which proves rapidly fatal, comes on very sud- denly—in twelve hours or even earlier after the poisoning. Such cases appear to occur with relative frequency when the doses are very large. In these cases there is often a severe affection of the nervous centres, as shown by the delirium, coma, and convul- sions, occurring especially in the form of an acute eclamptic attack. Paralysis is also not rare. Christison mentions this as the most frequent of the secondary symptoms in arsenic-poi- soning. This will be treated in detail under the head of Chronic Poisoning. The urine is sometimes albuminous or bloody. The perspira- tion is said to sometimes have an odor like that of arseniuretted hydrogen. The progress is usually rapid and fatal in more than one-half of the cases. Death generally takes place in from tAventy-four hours to four days, but in many cases after a few hours, and sometimes not until after the lapse of two Aveeks. Remissions, during which the patient is apparently better, often occur during the progress of a case. In cases terminating in recovery there may remain behind many sequela3, among Avhich may be men- tioned especially general emaciation, with ulceration and gan- grene of the skin, oedema, anaesthesia, and paralysis (especially of the lower extremities), and frequently also gastralgia, dys- pepsia, and chronic intestinal catarrh. The appearance of the cutaneous eruption in many cases is very peculiar ; an eruption like that of eczema and urticaria has been observed after both the internal and external application of the poison. Of course, those eruptions caused by its direct application to the skin are not referred to here. Post-mortem Appearances. After death from arsenic-poisoning the stomach presents the most characteristic appearances. The mucous membrane shows 650 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. signs of the most intense inflammation ; it usually has a dark- red color, which is distributed in spots or stripes. This color is not the result of simple corrosion, although particles of the poison are occasionally seen adhering to such portions of the mucous membrane, since precisely the same appearances are seen upon the mucous membrane of the stomach after death from the external application of arsenic. This inflammation is sometimes so severe as to produce hemorrhagic exudation or infiltration, which is often quickly folloAved by death of the tissue and ulcera- tion of the membrane. Ulceration may take place in a few hours ; in three cases, according to Taylor, this led to perfora- tion of the stomach during life. In some cases the signs of in- tense exudative inflammation are completely absent, as in one case in which Virchow found the appearance of acute parenchy- matous gastro adenitis, as he formerly described it, in connection with phosphorus-poisoning. Besides the above appearances in the stomach there is nothing characteristic in the cadaver ; eeclrv- moses beneath the endo- and pericardium, and imperfectly coagu- lated or fluid blood have been mentioned. More recently, since the discovery of fatty degeneration of the liver, etc., as a result of the action of arsenic, a similar condition of fatty and parenchy- matous degeneration of the muscular tissue of the heart, of the liver, etc., has been found in the bodies of those avIio have been poisoned. After arsenic-poisoning bodies do not putrefy, or only very slowly, but become mummified, so to speak. Usually the contents of the stomach and intestine contain the poison in those cases in which life has lasted only a few days at the longest, and if the arsenic was taken in the form of arsenious oxide, it is apparent as small granules, which are seen under the microscope to consist of small octahedral crystals. After a few days, how- ever, or even sooner, especially in cases where violent vomiting and purging have taken place, all of the arsenic may disappear from the contents of the stomach and intestine ; then it is found in the liver and other organs of the body, in which it can be detected very soon after it has been taken, especially if in very large doses. It is said to exist in the bones as calcic arseniate, a compound isomeric with calcic phosphate. After fourteen or fifteen days, however, it disappears from all of the organs. The ARSENIC. 651 elimination takes place in appreciable quantity with the urine and bile. In forensic cases it is of interest to know that arsenic can be detected in bodies which have been buried many years. Bodies do not absorb arsenic from the earth, even when that of the grave contains it, as it sometimes does. The tissues of the normal human body contain no arsenic. It is extremely improbable, to say the least, that arsenic can be fixed in the tissues of the body in more than the merest trace, after its long-continued ingestion in small amounts, as Avhen administered therapeutically. The treatment under all circumstances is to be directed to emptying the stomach ; in most cases, therefore, vomiting should be produced immediately, or the stomach-pump should be used ; any emetic is allowable, but it is best, if possible, to avoid using those substances which, like tartar emetic, strongly irritate the mucous membrane of the stomach. To counteract that portion of the arsenic not expelled from the stomach by vomiting, freshly prepared ferric hydrate or magnesia should be given in large amounts, and this treatment should be continued for days after the poisoning. The magnesia acts, at the same time, as a cathartic; otherwise care should be taken to produce abundant evacuations by the administration of cathartics, since if the arsenical compound formed with the antidote be allowed to remain long in the stomach or intestine, it acts as a poison, probably owing to its decomposition, so that the arsenious acid is set free. Moreover, all of the arsenic is never converted into a harmless compound, especially when it has been taken in the solid form, in which case small crystals of undecomposed ar- senious oxide are frequently found in the mixture of ferric hydrate or magnesia. Milk, albumen, etc., should be given at first to envelop the poison until the antidote or emetics can be obtained. In other respects the treatment of gastro-enteritis is to be employed. The dangerous collapse which always occurs indi- cates early and strong stimulation. 652 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. Chronic Arsenic-Poisoning. The same compounds which cause acute poisoning may also give rise to chronic. The ways in which the poison may get into the body are sufficiently numerous. In the first place, a mild form of chronic poisoning is not very rare as the result of the therapeutic use of Fowler's solu- tion. It results generally from using the drug continuously for weeks, but it may also come on quickly after taking the ordi- nary doses. More important are cases of professional poisoning, to which in its Avorst form workmen in arsenic mines are especially liable, and also those engaged in smelting ores which contain arsenic, although they are not worked for it; this is the case in smelting many of the copper, lead, and other metallic ores. We also meet with professional poisoning among those avIio work in ani- lin colors (fuchsin, etc.) and arsenical pigments (Scheele's and Schweinfurt green, arsenic red, etc.), among furriers, felt-work- ers, shot-makers, and workers in many metals, who frequently handle arsenic in alloys. Arsenic is also used in large amounts in glass-works for enamelling and decolorizing glass, but cases of poisoning from this source are unknoAvn. Those poisonings should be termed illegal which are caused by working with cloth, artificial floAvers, etc., Avhich are colored Avith arsenical pigments. Green tarlatan is very frequently col- ored with arsenical green, also artificial flowers, red and green, although, according to Pappenheim, less frequently. The loose manner in which the pigment is attached, especially to cloth, ren- ders it very easy for the poison to become diffused in the form of dust, and thus to give rise to poisoning in seamstresses and girls engaged in the manufacture of artificial flowers, and also in persons who wear these articles. Many green and red enamelled papers contain arsenic and may do injury, especially when used for wrapping confectionery. Toys are also sometimes painted with arsenical pigments. Red lacquer very often contains arsenic. The coloring of Avail-paper with arsenical green or red is inju- rious, not only to those engaged in its manufacture; there are a sufficient number of cases known in which chronic poisoning ARSEXIC. 653 has been produced by living in rooms furnished with such paper, and still more easily by living in rooms, the walls of AAdiich are painted with arsenical water colors. I myself saAv, tAvo years ago, a case of this kind, where three persons, employed in the Court-House at Konigsberg, suffered with undoubted symptoms of chronic poisoning. All of the chambers of the Court-House were painted yellow. Finally the following proved to be the explanation of the source of poisoning: The public documents heaped up in the repositories on the side of the walls had, by being placed in the compartments against the wall, gradually rubbed off the new yellow paint, and exposed to view an old green paint beneath ; this was also continually being rubbed off, and there was found upon and in the papers and in the compart- ments of the repository a thick layer of green-colored dust, Avhich, upon analysis by Dr. Blochmann (at that time assistant in the chemical laboratory at Konigsberg), was found to contain 8.32 per cent, of arsenious oxide. This dust—partly contained be- tween and in the folds of the papers—was diffused throughout the whole building by handling and carrying the documents, and would be found upon the table whenever a bundle of papers A\ras opened upon it. Other entirely similar cases, in which the detection of arsenic in the urine has verified the diagnosis, have long been knoAvn. In all such cases it is probably the arsenical dust which causes the poisoning. Fleck has, however, proved that arseniuretted hydrogen in small amount is developed in a mixture of arsenious acid and starch paste, yet this proves noth- ing in regard to the conditions here under consideration. The dust also appears to play the principal part in all other forms of chronic poisoning, with the exception of those which are caused by taking the arsenic internally. It is impossible to state the amount of arsenic necessary to produce chronic poisoning. Our knowledge of the conditions necessary for the understanding of the process is very incomplete. We frequently see the greatest variation in its effects upon dif- ferent individuals. It is a well-established fact that in Styria and other places there are persons (the so-called arsenic-eaters), who from early youth take arsenic in amounts of even six grains daily, or very often at least, and yet arrive at an advanced age 654 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. and remain in good health. The doses which in other cases produce severe chronic poisoning are evidently much smaller ; yet the above-mentioned amount of the poison is within the limit of a single fatal dose. It is everywhere stated that horses bear large doses of arsenic, and that it is often given to them to impart a well-nourished appearance. In all cases arsenic-poisoning is only manifested under the immediate influence of the poison, and not—as in the case of lead, for example—years after the removal of the person from its influence. It is true, however, that complete recovery is never possible after the disease has reached a high degree. No special predisposing conditions to the action of the poison are known, except the so-called individual idiosyncrasy, to which we must resort in this as in other forms of poisoning. The clinical history of chronic poisoning also does not appear to be well established, at least in all of its details. The usual results of the long-continued action of arsenic are angina, above all also conjunctivitis, and chronic gastric and intestinal catarrh, the latter characterized usually by constipa- tion, but sometimes by diarrhoea. If the poison acts in the form of dust, it produces an eczematous inflammation of the skin, attacking preferably the most vulnerable parts, such as the folds of the scrotum and axilla, and leading to excoriation and a ten- dency to death of the superficial layers of the skin. In severe poisoning the deleterious action of the arsenic upon nutrition is never wanting : a grayish cachectic appearance, all kinds of anae- mic troubles, headache, pain in the limbs, falling out of the hair and even of the nails, both with and without the formation of ulcers at the edge of the nails, mental depression and apathy, sleeplessness, etc., belong to the symptoms of such a case ; Aveak- ness like that of paralysis, and imperfect sensibility, are fre- quently mentioned. True paralysis, limited to certain nerve- tracts, is a more frequent sequel of acute than of genuine chronic poisoning. In such cases it appears during the first few days, or sometimes not until later, during the second or third week or even not until still later. Christison, who has given a good col- lection of the cases in question, mentions that of Dehaen in which the first symptoms of commencing paralysis did not ap- ARSENIC. 655 pear until after the patient had completely recovered from the symptoms of acute poisoning, and had felt entirely well for three successive days. Compare also the cases of Schaper. The paralyses usually develop gradually, and without notice- able evidences of inflammation; these are, however, by no means always wanting, especially at the beginning and in paraplegic forms. Contractures are frequently mentioned, and remain per- manent in cases which are not cured. Often a single extremity alone is affected. If the paralysis attacks several limbs, it is usually paraplegic ; paralysis of all four extremities occurs. It is generally stated that the extensors are more severely affected than the flexors ; atrophy of the affected limbs is frequently present, although it may be Avanting even in complete paralysis which has lasted for years. Little is accurately knoAvn concern- ing the affection of the sensibility. The bladder and intestines are not affected. In the majority of cases recovery from the paralysis takes place, yet a large number are known (Christison, Schaper, and others) in which it remained of constant intensity during lives which lasted many years. Of the complications, pulmonary phthisis has been mentioned as the one most frequently occurring. General dropsy is always noticed as the final symptom, but nothing is known concerning its connection with renal disease. Theoretical and Experimental Considerations. Those facts which are known concerning the absorption and elimination of arsenic (arsenious acid) have already been men- tioned ; it need only be stated here, that the poison is, according to Bergeron and Lemattre, probably eliminated with the SAveat, as well as with the urine and bile ; we wish also once more to dwell upon the fact that arsenic does not, like the heavy metals, remain a long time in the living body, but is in the course of a few weeks completely eliminated. It has been established experimentally, since the investiga- tions of C. Schmidt, that an important part of the action of arsenic is to diminish the elimination of carbonic acid and urea 656 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. even during starvation, that is, to diminish tissue-metamorphosis. On the other hand, the not unequivocal fact was referred to, that the temperature of the body is lowered by taking small doses of arsenic. The most recent experiments of Boeck have, however, thrown some doubt upon this statement as to the action of arse- nic in diminishing tissue-metamorphosis. A further interesting property of arsenic is the fact, discov- ered by Saikowski, that in animals its use causes the speedy dis- appearance of glycogen from the liver. This depends upon the fact that the arsenic acid prevents the change of the sugar to gly- cogen. In some experiments performed by me with starving rab- bits, which received on the third day of starvation or later an injec- tion into the stomach every two hours of from one to two and a half drachms of sugar with three-tenths of a grain of arsenious oxide, there was always found in the liver a very small amount of glycogen, the maximum being 0.15 per cent, of the fresh tissue. No sugar appeared in the urine. Compare also Lehmann. The observations made by Kunze are familiar—namely, that the heart of warm-blooded animals, killed immediately after the injection of small amounts of arsenic into the veins, continued to .pulsate for a long time (twenty-four hours) after the death of the animal. The power of arsenic acid to prevent fermentation, etc., is well known, so that it is natural that its above-mentioned action upon the living organism should be considered as connected with its property of arresting fermentation. But against this theory it should above all be remembered that the true processes of fer- mentation in the organism, such as the gastric digestion, are according to Boehm and Schaefer, not arrested by arsenic. In regard to the action of arsenic upon individual organs Sklarek found that, when injected subcutaneously, it produced a slowing and cessation of the heart's action in froo*s. It also produces paralysis of the nervous centres. This effect of arsenic was first made known by the labors of Boehm and Unterberger. The failure of the heart depends upon the complete paralysis of the abdominal vessels, and its paralyz- ing effect remains limited to the vessels in this region, when it is injected into the blood as well as when it is taken into the stom- ARSENIC. 057 ach ; when applied by the latter method the poisoning takes place more quickly and more intensely. The elimination of the poison takes place from the blood through the mucous mem- brane of the stomach and intestine, but this is too slight to warrant the supposition that the local action of the arsenic so eliminated is of importance. On the contrary, Boehm favors the view that in all cases the symptoms of arsenic-poisoning here men- tioned must be referred to the effect of the arsenic from the blood. Against this, however, it must be remarked that, when applied to the skin, it exhibits a local in addition to its general action. Mention has already been made of the discovery of Saikowski, who found great fattening of the liver, kidneys, and muscular tissue ; he found a larger amount of fat in the liver than in his experiments upon phosphorus-poisoning. Free arsenic oxide does not possess any corrosive action; at least it forms no compound of albumen. Its powerful local inflammatory action upon the mucous membranes, as well as upon the skin, has not been sufficiently explained. It follows from the above that it is at the present time impos sible to give any theory which will satisfactorily explain arsenic- poisoning. The above-mentioned work of Boehm forms, however, a most important contribution in this respect. Yet in human poisoning it is impossible to consider the single symptoms sepa- rately as to whether they are to be ascribed to the local irritation or to the general action of the poison. There is no question that it does act as a local irritant; yet it is difficult to say in single cases how much of the inflammation of the stomach, after it is taken internally, for example, is dependent upon this and how much upon the general action. There is, moreover, no doubt that the symptoms of collapse depend directly upon its action on the heart and blood-vessels, or upon the nervous centres, but, on the other hand, it seems sometimes to depend also upon the violent gastro-enteritis, etc. The treatment of chronic arsenic-poisoning can only be pro- phylactic. If anything shoAvs the importance of sanitary laws, it is this fact that at the present time arsenical clothing, wall- paper, etc., are daily sold in the shops. On account of the importance of this substance in many in- VOL. XVII—42 658 NAUNYN.—POISONING BY THE HEAVY METALS, ETC. dustries, and on account of its very low price at the present time, no attempt can be made to materially diminish the danger to workmen in the arsenic mines, except by the simplest means ; in regard to what can be done in this respect, we must refer to the copies of the Saxon regulations.] No antidotes are known ; remedies to hasten its elimination are unnecessary. It may be mentioned that Mueller asserts that he has observed that potassium iodide hastens its elimina- tion. In addition, therefore, to the prophylactic treatment—that is, sanitary regulations,—nothing remains, except that which is usually employed with persons who are feeble, and who suffer from those affections which go to make up the group of symp- toms. Arseniuretted hydrogen poisoning has thus far only been observed experimentally in animals, and as the result of hand- ling it incautiously by the chemist in the laboratory. That arseniuretted hydrogen is the active agent in cases of poisoning by wall-paper is not proved, and is, moreover, to judge from the symptoms seen in such cases, highly improbable. Finally, the symptoms of simple chronic arsenic-poisoning are totally differ- ent from those of arseniuretted hydrogen poisoning. Of this we know only the acute form, which is caused by inhaling very small amounts of the gas, produced by the development of hy- drogen in solutions containing arsenic, or in large quantities by treating the arsenide of zinc (an alloy of arsenic and zinc) with dilute sulphuric acid. The symptoms of arseniuretted hydro- gen poisoning consist of vomiting with pain in the region of the stomach, headache combined with prostration, and abundant haemoglobinuria. The last symptom must be due to the power of the arseniuretted hydrogen to decompose the blood-globule. The cases which have been observed in human beings have usually proved fatal, but recovery frequently takes place in ani- mals, if too much of the gas has not been absorbed, and if the haemoglobinuria has not been too abundant. The post-mortem examination leads to negative results. Nothing is known concerning treatment. 1 Pappenheim, I. p. 168. VEGETABLE POISONS. 5 VON BOECK. POISONING WITH ATROPINE. Atropine, GnH23N03, is one of the most powerful vegetable poisons. It was discovered in 1831 by Mein, and in 1833 by Geiger and Hesse in the deadly nightshade (Atropa Belladonna). It forms colorless, columnar, and acicular crystals, glossy as silk ; it has a bitter taste; is sparingly soluble in water, but readily so in chloroform, alcohol, and amylic alcohol. It is to be found in several plants, and for this reason, as well as on account of its frequent use in medicine, poisoning by it often occurs. Daturine, which was formerly regarded as an inde- pendent alkaloid, has been proved to be identical with atropine in its chemical as well as its physiological action.1 Etiology. In Germany atropine is chiefly found in the Atropa Bella- donna, which is very common in our woods, and the similarity of its berries to small black cherries leads to poisoning. A num- ber of poisoning cases arising in this manner, especially among children, have been recorded; even the specimens cultivated in botanic gardens have sometimes occasioned poisoning. Orfila2 de- scribes in detail the effects of deadly nightshade berries upon 500 soldiers, who had plucked and eaten them in a wood near Pirna (Dresden). But poisoning has also often arisen from the leaves having been mistaken for the leaves of various innocuous plants.' The family of an Italian herb-collector, numbering five persons, 1 See the researches of Planta. Also Husemann, Pflanzenstoffe. p. 434. 2 General Toxicology, translated by Hermbstaedt. Berlin. 1818. 3. Thl. p. 271. • 3 Stokm in Amsterdam, Archiv fur path. Anat. XLIX. 1869. S. 450; also Journ. de chimie med. 1869. Mai. p. 210. 662 VON BOECK.—VEGETABLE POISONS. were poisoned by food having been prepared in a vessel which had not been cleaned after having been used for boiling deadly nightshade leaves.1 Cases of poisoning have also been recorded from human beings eating the flesh of animals which had fed on belladonna leaves without danger to themselves ; among the ani- mals to which atropine is innocuous are rabbits, pigeons, rats, and guinea-pigs. Some years ago this circumstance was the sub- ject of a trial in an American court of law.2 Bouchardat3 men- tions cases of persons having been poisoned by eating snails in vineyards, which had fed upon the leaves of the deadly night- shade. There are numerous instances of poisoning by preparations of belladonna used medicinally, as, for instance, by taking too large doses of the extract, by mistaking a belladonna liniment for a draught to be taken internally, and even from its outward appli- cation. Indeed, cases are known in which poisoning has occurred from the application of a belladonna plaster to the skin, or the rubbing-in of belladonna liniments.4 Even the application of a solution of atropine to the eyes has frequently produced poisoning, either through simple absorption of poison by the conjunctiva, or by a portion of the atropine escaping through the small lachrymal ducts into the nostrils or the throat, and there becoming absorbed.5 Thus Richet6 tells of an old man who had one drop of solu- tion of atropine (1: 100) dropped into his eye twice a day, and after eight days became violently delirious ; the delirium disap- peared with the discontinuance of the remedy. A similar case is recorded by Jos. Laurenzo of Bahia.7 1 G. Martino, Storia di sette persone avellenate dall' estratto di Belladonna e guaribe. Ann. univers. di med. Juglio. 1872. 2 Pharmaceutical Journ. and Transact. Ser. II. Part 7. p. 127. 3 Compare Husemann, Handbuch der Toxikologie. Berlin, 1872. p. 281. 4 Peroud, Americ. Journ. LXXXVIII. p. 403. Oct., 1862; Lopez, Americ. med. chirurg. Rev. March, 1860, p. 285; Jenner, Med. Times and Gaz. Nov., 1857 ; Morisse, Journal de Toxicolog. Avril, 1859; Rossignol, Lancet. 11 Nov., 1865; together with a number of other records. 5 Chassaignac Lauzer in Revue therap. 1854. p. 266. 6 Gaz. des Hopit. 79. p. 285. 1869. 1 Gaz. des Hop. 123. 1869. ATROPINE. 663 Many cases of poisoning are also attributable to the thorn- apple (Datura Stramonium); they generally arise out of mistakes in cookery ; especially the seeds of stramonium are very poison- ous. Schneider, in Casper's Wochenschrift,1 has contributed a tolerably full account of the pharmacological and toxicological records on this subject handed down to us from former times. Fresh instances have occurred in modern times; thus Ploegel2 wit- nessed a case of poisoning by the tincture of stramonium ; Ley- gey, 3 one by the seeds; Turner also,4 Kuhorn,5 Rogers,"and others. Stramonium has also been employed for committing suicide, as in the case reported by Lichtenfels.7 It has also been used as a poison with the intent of robbery or murder ; for instance, the natives of India are in the habit of poisoning English soldiers with a sweetmeat containing the seeds of the thornapple for the purpose of robbing them; Th. Anderson gives a case of this kind.8 On another occasion atropine9 was given to an old man in his milk, and he died in five hours. Even by subcutaneous in- jection of atropine (daturine) very dangerous cases of poisoning have arisen.10 As to what constitutes a poisonous dose, it must be borne in mind that children can tolerate comparatively very large doses of belladonna, particularly when they are suffering from nervous complaints—chorea, for example; thus H. W. Fuller11 observed that a girl ten years of age, suffering from chorea, took every day for twenty-six days 70 grains of the extract of belladonna = 1019 in all; another girl of fourteen took in eight days 37 grains Avithout the smallest injury, whereas in the case of adults even 2 grains may produce unmistakable symptoms of poisoning. 1 Der Sfcechapfel als Arznei u. Gift. Casper's Wochenschr. No. 37. 1848. 2 Wien. med. Halle. II. 42. 1862. 3 L'Union. 6. 1862. 4 Amer. Journ. of Med. Sciences. April, 1864. 5 Bull, de Therap. LXX. p. 285. 6 Philad. Med. and Surg. Rep. Aug. 31. p. 211. 1872. ' Wiener Zeitschr. N. F. I. 37. 1858. 8 Edinburgh Med. Journ. V. p. 1100. June, 1860. s T. Crace Calvert, Pharm. Journ. 1872. pp. 596, 617, 663. 10 E. g., Charles Carrol Lee, Amer. Journ. of Med. Science. Oct., 1862. p. 404. 11 Med. Times and Gazette. July 23, 1859. 664 VON BOECK.—VEGETABLE POISONS. As a general rule, however, belladonna and atropine act as very powerful poisons, even in very small quantities. In a case given by J. Seaton,1 one single nightshade berry Avas sufficient to produce severe symptoms of poisoning in a young man ; in another case given by Bauer,2 a child nine months old died in twenty-four hours from having eaten three berries. A teaspoon- f ul of belladonna liniment swallowed by mistake killed a woman sixty years of age, in spite of all antidotes.3 Yet it is a fact that sometimes very large doses can be borne, and that often cases which appear to be very serious end in recovery. Thus, a Berlin physician took nearly half a grain (0.03 gramme) of pure atropine and recovered,4 whereas another5 takes five and a half grains (0.36 gramme) of atropine and dies ; a girl two and a half years old takes a fourth of a grain of atropine and recovers, in spite of very alarming symptoms.6 A lady in Philadelphia takes instead of three grains of assai'cetida, the same quantity of atropine, and dies in fifteen hours.7 I myself witnessed a case in which a man, sixty years of age, who had taken by mistake one-quarter grain (= 0.015 gramme) of atropine, recovered, notwithstanding very violent symptoms. In general, we may say that one-twelfth of a grain of atropine may produce poisoning, but that death ensues very rarely even from three-quarters of a grain. Preparations of belladonna and stramonium naturally act according to the proportion of atropine which they contain. The root of the night- shade contains, according to Schroff, the most atropine (one part in three hundred), the leaves contain less; the various extracts and tinctures are again very different in strength ; so that it is impossible to give any exact figures for them. Taylor saw a young man of sixteen, who had taken a drachm of extract of belladonna, die in three and three-quarter hours, while a woman 1 Med. Times and Gaz. Dec. 3. 1859. s Wurtemberg. Corresp.-Bl. 1873. p. 113. 3 Beddoe, Lancet. 1870. July 16. p. 83. 4 Siegmund, Virchow's Archiv. XLVIII. p. 188. 1869. 5 Pollack, Wiener med. Presse. 1870. p. 565. 6 Kuethe, Nederl. Tijdschr. f. Geneeskunde. Afd. 1. p. 497. 1870. ' Gross, Americ. Med. Journ. Oct. 1869. p. 401. ATROPINE. 665 who had taken the same quantity recovered in twelve hours. The German Pharmacopoeia fixes as maximum doses : Per dose. Per diem. Of belladonna leaves 0.2 (gr. 3). 0.6 (gr. 9). Of belladonna extract 0.1 (gr. 1£). 0.4 (or. 6). Of belladonna tincture 1.0 (ttl 15). 4.0 (m 60). Of atropine sulphate 0.001 (gr. ^). 0.003 (gr. &). Of belladonna root 0.1 (gr. 1£). 0.4 (gr. 6). Atropine-poisoning takes place when the alkaloid has en- tered in sufficient quantity into the fluids of the body; the manner in which it enters the body is not of much importance ; in addition to the ways already mentioned, poisoning may also be brought about by enemata of infusion of belladonna, and by suppositories which contain extract of belladonna. The symptoms consequent upon the introduction of atropine usually set in somewhat rapidly, as absorption by the mucous membrane of the stomach and intestines proceeds with consider- able rapidity. Pathology. Nature and Course of the Illness. In general, poisoning by atropine produces effects similar to those of most other narcotic poisons. The poison first attacks the brain, especially the sensorium, but then it invariably in- fluences the cardiac pulsations and the condition of the pupils. As regards the sequence of symptoms, we Avay safely follow Schneller and Flechner,2 who observed this sequence in experi- ments on themselves ; and their statements, as to the more impor- tant data, have been confirmed by Bouchardat and Stuart Cooper3 and Lusanna,4 whose experiments are more recent. 1 S. Taylor, von Seydeler. III. Bd. p. 375. 2 Beitrage zur Physiologie der Arzneiwirkungen. Zeitschrift der Wiener Aerzte. 1847. Juni. 3 Recherches optiq., physiolog., therap., et pharm. sur l'atropine. Gazett. med. de Paris. 1848. Nos. 51 und 52. 4 L'Union med. No. 77. 1851. 666 VON BOECK.—VEGETABLE POISONS. The first symptom is dryness of the palate, subjectively and objectively, furred tongue, tickling in the throat, hoarseness, difficulty in swallowing and speaking, nausea, inclination to vomit. These symptoms, especially the dryness of the throat and palate, generally set in fifteen minutes after the poisoning. They are usually attended with violent thirst.1 Brain symptoms next appear : giddiness, headache, slight stupor, confusion of mind, dejection; to these are added hallu- cinations of the sight and hearing, various in character, often of a cheerful nature. Then follow disturbances of the organ of sight: weak-sightedness, seeing things in a mist, and objective suffusion of the vessels of the conjunctiva and dilatation of the pupils ; then follow in most cases difficulty in micturition, the urine often flowing drop by drop and with pain; and finally, peculiar appearances on the surface of the body are observed : dryness of the skin, scarlet redness, cedematous swellings, etc. In severe cases the preceding symptoms are developed with considerable violence. Thus the dryness of the palate and throat amounts to absolute impossibility of swallowing (aphagia), not even liquids can be swallowed ; many patients in this condition shrink so much from the act of swallowing, that they forcibly resist, if anything is offered to them; children, according to the observations of Schaeffer,2 are inclined to bite. Objectively we find very little secretion on the reddened mucous membrane, m the region of the salivary glands, or on that of the mouth itself. The heart and the vascular system joresent a series of especially noteworthy symptoms; in the first place perhaps a slight retarda- tion, but later on an enormous acceleration of the cardiac pulsa- tions occurs, which in the human subject may rise to 150 and 190 beats per minute.3 If the poisoning is fatal, the heart finally becomes paralyzed, and then the heart, before it absolutely ceases to beat, will perform its contractions more slowly but irreo-ularlx 1 Tissore, Empoisonnement par la belladonne. Gaz. med. de Paris. 1856. No 12 2 Sobernheim also mentions such a case in his Handbuch der prakt. Arzneimittel- lehre. Berlin, 1847. p. 6, taken from the Gaz. med. de Paris. 1835 No 17 3 C. Holthouse, Med. Times and Gaz., Dec. 1859, observed in a child four years oi age, who had been poisoned with from 3 to 4 grains (=0.18-0.24) of sulphate of atro- pine, a pulse of 170 per minute. ATROPINE. 667 and with little energy. The vessels, especially the carotid and temporal arteries, throb very violently, the peripheral vessels are enlarged ; hence we get injection of the conjunctival mucous membrane, and great protrusion of the eyeballs. This enlarge- ment of the vessels shows itself chiefly also on the surface ; the face is generally of a livid redness, and is subjectively and objec- tively hot; but frequently the rest of the body also is covered with a scarlet exanthem, which either affects the upper part of the body only or, in rare cases, extends to the lower part. In spite of this hyperaemia of the skin, perspiration is suppressed, and the skin is dry to the touch. These cutaneous symptoms often follow upon very small doses of atropine. Thus Sidney Ringer ' asserts that joo grain (=0.0003) of atropine subcutaneous- ly injected arrests perspiration, and J. G. Wilson 'i saw two cases of lying-in women, who had had belladonna ointment rubbed on their breasts to produce galactostasia, and upon whom a scarlet eruption came out, which lasted three or four days, and disap- peared sooner than the dilatation of the pupils. Th. Stadler3 saw a similar eruption appear upon a child three months old, within a few minutes after the administration of ^ grain (= 0.0003) of atropine sulphate for whooping-cough. It lasted five hours ; smaller doses brought out a similar eruption each time, but of shorter duration. A desquamation of the epidermis often succeeds this eruption. Corresponding to the condition of the heart and the vessels, the pulse—which at first was full and hard—becomes soft, easily compressible, the blood-pressure is considerably reduced, and the temperature of the body is invariably diminished. The distention of the jugular vein, which has been observed in many cases,4 and the swelling of superficial veins generally 5 with occasional oedema,6 are referable to the depression of the action of the heart and diminished pressure of the blood. 1 On the Influence of Belladonna in Sweating. Practitioner. July. p. 93. 1873. * Two cases, etc. Glasgow Med. Journ. Feb. p. 198. 1872. 3 Med. Times and Gazette. April 11, 1868 4 Bonassies, Empoisonnement par la belladonne. Journ. de Chim. Med. Nov. 1844. 5 Trapenart, L'Union. 1859. p. 147. 6 Storer, Brit Med. Journ. May 4, 1870. 668 VON BOECK.—VEGETABLE POISONS. With regard to respiration, its frequency is, in the early stage of the poisoning, diminished ; subsequently it is steadily increased till towards the final stage, when it again sinks to the normal rate, or becomes sloAver and slower till it ceases alto- gether. We' also find in many cases a severe laryngitis excited, to- gether with pain in the larynx, roughness and hoarseness of the voice, and the separation of a white transparent secretion from the mucous membrane of the larynx and bronchi; this Avas observed in two cases by Morel.1 One of the most 'distinctive symptoms of atropine-poisoning is dilatation of the pupils, which, even with minimum doses (according to Donders ouWo Sr- =0.00000046), lasts for several hours. When it is dropped into the eye, only the one pupil is dilated, whereas in cases of general poisoning by atropine, both eyes are almost always equally affected. If somewhat larger quantities are introduced, the pupils are dilated to the maximum, remain motionless, no longer react to light, and thus a number of other symptoms are developed; for instance, a variety of dis- turbances in the power of seeing, utter incapability of focalizing the eye, prismatic vision,2 double vision, occasionally micropsia, and sometimes complete amaurosis. This mydriasis with its consequences sets in quite constantly, and may last a very long time : thus, for example, Gubler3 states that in one case it lasted fourteen days; at any rate, it is the symptom of atropine-poi- soning which is the last to disappear; indeed, it has been ob- served to last as long as three or four weeks. The supposed amaurosis of many observers4 is only apparent, and is the result of the loss of the power of focalizing. The chief effect of atropine, that upon the brain, manifests itself in a double form : first, a series of disturbances appear in the sphere of motility, and then considerable disturbances arise 1 Trois cas d'empoisonnement par la belladonne. Annal. de Societe med. de Gand 1872, Sept. 181. 2 Stokvis mentions, Arch. f. path. Anat. XLIX. p. 450. 1869, a case of a man wh< saw the edges of all objects prismatically colored. 3 Commentaires therapeutiques du codex medicamentarius. Paris 1874 n 746 4 Evans, Brit. Med. Journ. Sept. 21, 1861. ATROPINE. 669 in that of sensibility. With regard to the motile changes, the most striking point is that, as a rule, soon after the setting in of the first symptoms of poisoning, a general jactitation of the body takes place, in many cases accompanied with pains ; crying and screaming, especially with children, are common. Many patients in this jactitatory state make free use of their muscular strength, crush to pieces all that comes into their hands ; but shortly after there supervenes a disturbance in the co-ordination! of these move- ments ; many lose the poAver of walking straight, stagger about, cease to be able to articulate clearly; even cases of aphasia2 and alalia are recorded. More rarely, convulsions occur, generally clonic,3 seldom tonic spasms; still tetanus, especially opistho- tonos, has been seen. Sometimes very peculiar disturbances of the locomotor system appear ; thus a miser, who intended to steal turnips in a field, but pulled up hyoscyamus roots instead, paid the penalty of the theft by being seized with a dancing-frenzy accompanied by convulsive laughter. Dysphagia also is sometimes the result of contraction of the muscles of deglutition, for in the Tissore case, Avhen a finger was passed into the gullet, it Avas found to be firmly contracted, so that an emetic could only be administered by an oesophageal tube. So also the dysuria, Avhich occurs in so many cases, is to be attributed to cramp of the detrusor vesicae urinarise. The symptoms connected with the psychical functions of the brain are more constant and more important. The first symptom is generally giddiness, swimmings in the head, abnormal sensa- tions, especially of sight and hearing; hallucinations are also very common, and delirium is superadded, so that the general 1 See, for example, the case of Stevens (referred to on p. 680). 5 Paget-Blackc, Reports of St. George's Hospital. III. 160. 1868. An asthmatic patient took about one drachm and a half of tincture of stramonium. The usual symp- toms followed ; later on actual aphasia set in, so that he called everything by the wrong name. 3 In a case described by Trapenart (l'Union. 147. 1859), of a lunatic, thirty years of age, who had eaten some nightshade berries, trembling of the hands and twitchings in the whole upper part of the body came on; the same thing occurred in the case of a girl who had taken i gr. of atropine {Kuethc, Nederland. Tijdschr. f. Geneesk. Afd. I. p. 497. 1870). In the case, already cited, of Bonassies, cramps in the fingers came on, which gradually extended to the trunk and the other parts of the body. 670 VON BOECK.—VEGETABLE POISONS. condition may be characterized as one of mental aberration with delirium. These attacks of delirium may be quiet or they may be vio- lent, and they sometimes continue till coma sets in. After the jactitation has lasted for some time—the length of time depends upon the quantity of the poison—it gives place to lassitude and a feeling of sleepiness, which generally passes into complete sleep; the stage of narcosis. This sleep becomes gradu- ally deeper, patients cannot be roused from it by any means, the eyelids are only half closed, and this somnolent and comatose condition, in which, with the exception of the so-called automatic action of the heart and of the respiratory muscles, there is no voluntary or reflex movement, again disappears gradually, or ends in death. In many cases, especially those that end fatally, the contents of the bladder and of the bowels are passed in- voluntarily, in consequence of paralysis of the sphincters in this stage of narcosis. In a few cases fits of delirium and stupor alternate, and these intermitting or remitting cases are those in which the prognosis is more favorable. Among the rarer symp- toms of atropine-poisoning we may mention erotic manifestations which take place during the stage of excitement, priapism,1 etc. Parsons 2 gives an instance in which a man's hair turned gray during atropine-poisoning of short duration. A case communi- cated by Evans3 is also worth mentioning, in which a girl nine years of age had eaten four nightshade berries, and after six hours tympanites in an aggravated form set in. As regards the duration of the poisoning process, death gener- ally ensues within twenty-four hours, rarely within five or six hours, and more rarely still not for thirty hours. Convalescence is always very slow, never sudden ; the pulse and respirations very gradually return to their normal rate; subsequently sensi- bility is restored, and the sensorial disturbances cease. There are cases in which, after somewhat large quantities of atropine have been taken, four days, and even more, are required for re- covery. 1 Schmid, Monatsblatter fiir Augenheilkunde. II. p. 158. May 1864 s Brit. Med. Jour. 25. Dec, 1869. p. 675. 3 Ibid., 21. Sept., 1861. ATKOPINE. 671 As sequelae, mydriasis lasts for some time, sometimes accom- panied by slight focal disturbances. The aphasia which we mentioned above lasted for a considerable time, and the patient, during his convalescence, called almost everything by the wrong name. There are, therefore, no actual sequelae in cases of atro- pine-poisoning, although occasionally hemorrhage in the brain has occurred, followed by prolonged hemiplegia, yet these are only indirect results of the poisoning. Atropine kills by paralyzing the heart in the first place, but perhaps also, in some cases, by exhaustion of the respiratory centre. Analysis of Symptoms. Character of Atropine-Poisoning. Recent experimental investigations supply a fairly satisfac- tory pathological basis for a number of the symptoms of atro- pine-poisoning. Another large group of symptoms, however, must simply be accepted as fact. The dryness of the palate is to some extent accounted for by the experiments which Heidenhain, Bezold and Bloebaum, Keu- chel also, have made on the salivary glands of animals. We know by the researches of Ludwig, Czermak, Bernard, that irri- tation of the tympanico-lingual nerve which arises from the chorda tympani, and accompanies the trigeminus, leads to the secretion of a quantity of thin saliva in the submaxillary gland, at the same time accelerating the flow of blood through the gland and heightening its color. Heidenhain1 has shown that irritation of the fibres of the chorda tympani in atropine-poisoning accelerates the flow of blood, but does not cause secretion of saliva, whereas excitement of the sympathetic causes the secretion of a small quantity of thick viscid saliva as in the normal condition. Keuchel had before observed this fact.2 The mydriatic effect of atropine is a favorite subject for ex- periment. 1 Arch. f. d. ges. Physiolog. V. 40. '2 Das Atropin und die Hemmungsnerven. Dorpat. 1868. 672 VON BOECK.—VEGETABLE POISONS. Hitherto the view has been universally accepted that dilata- tion of the pupil follows directly upon the use of atropine, but Rossbach and Froehlich maintain that in the case of frogs and rabbits dilatation is preceded by contraction, slight and transient indeed, but quite perceptible Avhen very small doses of atropine (one-one-hundredth and less) are administered. Whether this proceeds from paralysis of the oculo-motor nerve, or from excitement of the sympathetic, or from both factors simultaneously, is still a subject of controversy. It is pretty clearly proved that the sphincter iridis and its nerve, the oculomotorius, are paralyzed by the poison. Indeed, the cir- cumstance that the tensor chorioidea?, supplied by the same nerve, becomes also paralyzed, strongly supports this view ; but still more the fact (according to de Ruiter's experiments), that an electric shock given to the iris while the eye was under the influence of atropine produced no contraction of the pupil, which always occurs when the eye is in the natural condition. Lastly, the absence of all reaction to the impression of light, even when the sympathetic has been divided, affords almost certain proof to the same effect. The most direct proof of this theory, how- ever, is furnished by the experiments of Bernstein and Dogiel ;' these investigators irritated the oculomotorius within the cra- nium of the atropinized animal, ■ without producing contraction of the pupil. That the muscle of the iris, as such, is not para- lyzed, the authors just mentioned prove by the fact that in the same experiment direct excitation produced contraction of the pupil. The second question, whether atropine does not simultane- ously excite the sympathetic and the dilatator pupillae supplied by it, is more difficult to answer. In favor of this view, the testimony of Cramer2 may be quoted, who says that after sec- tion of the cervical sympathetic on one side, followed by atro- pine-poisoning on the side operated upon, a slighter mydriasis followed than upon the uninjured side. Another argument for this theory is, that the extent of dilatation of the pupil cannot 1 Bernstein und Dogiel, Verhandlungen des nat. med. Vereins zu Heidelberg. IV 2 Het accomodatic Vermogen der oogen. Haarlem. 1853. 127 ATROPINE. 673 well be accounted for by a mere preponderance of the action of the dilatator consequent upon the inaction of the sphincter, and also that no further dilatation can be produced by direct excitation of the iris, because the dilatator has already been contracted to its maximum. But doubt is again thrown on this conclusion when we remember that Gruenhagen1 and Hirsch- mann2 both succeeded in increasing the dilatation caused by atropine by exciting the sympathetic, and that H. Braun,3 more- over, proved that, six months after the section of the sympa- thetic, by which time the terminations of the sympathetic in the pupil must have been long degenerated, dilatation still followed the use of atropine. For the present, therefore, we must regard the influence of atropine on the dilatator pupillae as doubtful, even though Braun's experiment may seem to point to the oppo- site conclusion.4 The fact that, in local application of atropine to one eye, dila- tation of the pupil of only that eye followed, combined with the observation made by Fleming,6 that when he very carefully con- veyed the poison only to one side of the eye, dilatation of the pupil first appeared on that side, seems to indicate a local action of this poison. But then, again, we are almost compelled to admit, with Bezold and Bloebaum, supported by L. Hermann,8 that nervous centres exist in the iris itself; that these really must reside either in the iris or its immediate neighborhood, is proved by Ruiter's statement,7 that even in an excised frog's eye mydriasis can still be produced, when all other nerves are ex- 1 Centralbl. f. d. med. Wissenschaft. 1863. 577. 2 Arch, f. Anatomie u. Physiol. 1863. 309. 3 Arch, fiir Ophthalmolog. V. 112. * Strong evidence of active contraction of the dilatator by atropine is afforded by the often observed fact that the passive dilatation ensuing upon paralysis of the oculo-moto- rius is never as great as that induced by atropine, and that in such condition the dilata- tion is greatly increased by atropine, whether locally applied or introduced into the gen- eral circulation. The writer of this note has, with many others, proved such increased dilatation by local applications of atropine to human eyes affected by idiopathic abso- lute paralysis of the oculo-motorius.—E. Curtis. 5 Edinburgh Med. Journ. 1863. « Lehrb. d. experiment. Toxikologie. Berlin. 1874. p. 335. 1 Nederlandsch. Lancet. III. 433 ; also loc. cit. p. 83. VOL. XVII.—43 674 VON BOECK.—VEGETABLE POISONS. eluded. It is very probable, therefore, that atropine exerts its chief influence upon these nerve-centres. The loss of power of accommodation, disturbances of vision, etc., which have been observed in atropine-poisoning, are the result of the dilatation of the iris and paralysis of the tensor chorioideae. The action of atropine upon the heart and its movements has been reduced to a sound pathological basis by experiments on animals. Von Bezold and Bloebaum, and Keuchel, are the chief authorities for the action of atropine upon the heart. The acceleration of the pulse following upon section of the vagus in otherwise healthy animals was not increased by atro- pine-poisoning afterwards ;' again irritation of the vagus in atro- pinized animals failed to retard the pulsation of the heart. This proves that the extremities of the vagus in the heart after a slight excitation, which produces the transient and not very important retardation of the pulse at first, must have been para- lyzed by the poison. Rossbach and Froehlich were the first to call attention to the original initial irritation of the extremities of the vagus. The question, whether the extremities of the branches of the vagus or the intermediate ganglia are paralyzed by atropine, is decided by Boehm's2 experiment in favor of the former. He failed to arrest the atropinized heart of a frog by irritating the sinus. Schmiedebergs was equally unsuccessful with muscarine. While atropine is found to be incapable of acting on the sym- pathetic, its influence on the excito-motor ganglia of the heart is considerable. Von Bezold and Bloebaum (loc. cit.) have shown that these centres of cardiac innervation are completely para- lyzed by tolerably large doses of the poison: the pulsations of the heart and the pressure of the blood diminish, Avhen atropine is administered to an animal after section of the vagus and the cervical marrow. But the cardiac muscle also loses its excitability and becomes 1 Exactly the opposite has been affirmed as the result of experiments by Lemattre {Archives Generates. August, 1865) and H. C Wood {Therapeutics, Materia Medica and Toxicology, Philadelphia, 1876, p. 234).—E. C * Studien iiber die Herzgifte. Wiirzb. 1871. p. 14. 3 Berichte der sachs. Acad. d. Wissenschaft. Math. phys. Classe. 1870. 129. ATROPINE. 675 paralyzed under large doses. It appears, then, that atropine is eminently a heart-poison, which destroys life by arresting the action of the heart. Von Bezold and Bloebaum have further proved by direct ob- servation that atropine-poisoning in large doses is followed by distention of the small vessels, and that this distention is the consequence of paralysis of the vaso-motor nerve-centre, as the distention after injection of atropine into the peripheral end of the carotid takes place almost instantaneously. Accordingly, the pressure of the blood also decreases. Yet the blood-pres- sure does not decrease immediately after atropine poisoning ; on the contrary, it increases in the first instance, or, when small doses are used, corresponding to the frequency of the cardiac pulsations, and to the initial contraction of the arteries. The contraction of the arteries has been demonstrated by Meuriot,' at least in the case of the web of the frog, upon appli- cation of atropine. Fleming' and Hayden * had already observed this contraction ; the latter holds the contraction of the vessels to be a reflex action of the skin. This retardation of cardiac and vascular action fully accounts for the lowering of temperature observed in human subjects. The influence of atropine upon the respiratory organs, which in human subjects as in animals shows itself first by retardation, afterwards by acceleration, depends upon a paralyzing action on the pulmonary branches of the vagus, so that the peripheral stimulation fails to reach the central organ; hence the retarda- tion in the first instance. The subsequent acceleration, demonstrated by the researches of Bezold and Bloebaum, is caused by the irritant action of the poison on the respiratory centre. When the dose is very large, however, this central organ is paralyzed, whether by the poison itself or by exhaustion, or by carbonic acid poisoning, attendant on the onset of cardiac paralysis. The laryngeal fibres of the vagus, which in the normal condi- tion have a retarding influence on respiration, are not paralyzed 1 Gaz. hebdomad. 1868. Nos. 12, 15, 16. '- Edinburgh Med. Journ. 1863. 777. s Dublin Quart. Journ. 1863. Aug. 676 VON BOECK.—VEGETABLE POISONS. by atropine, as Keuchel' has proved ; therefore they have noth- ing to do with the acceleration of breathing. Thus, also, the variations in breathing, observable in atropine-poisoning, are easily and naturally explained. The influence of atropine upon the striped muscles and the motor nerves, which, as we have seen, in atropine-poisoning in human subjects takes the form of cramp, but which usually passes, after a short period of jactitation, into an absolutely motionless condition, is not very satisfactorily explained by the experimental evidence which we so far possess. Von Bezold and Bloebaum's experiments indicate, indeed, a diminution of the excitability of the motor nerves, but show that the muscle itself is scarcely acted upon by atropine ; as regards the motor nerves, these authors show that it is highly probable that the termina- tions of the nerves in the muscle primarily suffer diminution of their excitability, and that subsequent changes occur in the nerve-trunk. This loss of excitability in the motor nerves helps to explain the motionless state of those poisoned, but it does not explain the occurrence of the convulsions ; these are to be traced to changes in the nerve-centres. The inquiry into the action of a poison upon the sensory nerves is extremely difficult, and as the methods hitherto adopted are not altogether unexceptionable, the statements of Botkin2 and v. Bezold and Bloebaum (loc. cit.) on this subject are insufficient, though it appears fairly deducible from them that the excitability of the terminations of the sensory nerves is diminished by large doses of atropine. Still, practical clini- cal experience, especially in neuralgia, is calculated to give a stronger support to this theory than experiments on animals. Lastly, the influence of atropine on the brain and the spinal marroAv is very considerable, yet it presents even more obstacles to experimental research than that on the sensory nerves. In the human subject there are unmistakable symptoms of increase of excitability, and especially of actual excitement of the central portions of the nerves of the organs of sense, which is succeeded 1 Das Atropin und die Hemmungsfasern. Dorpat. Diss. 1866. 2 Botkin, Ueber die physiolog. Wirkung des schwefelsauren Atropins Virch Archiv Bd. XLII. 1862. ATROPINE. 677 by diminished excitability, sometimes passing into complete loss of consciousness and feeling. This effect upon the brain cannot be traced to disturbance of the circulation, but to direct action of the poison on the nervous elements. The spinal marrow also seems to be subjected to a like influence; according to Fraser1 the convulsions which have been observed in human subjects also appear in the frog after large doses, but not till towards the close of the action of the poison ; they begin with rigidity of the forefeet, then of the hindfeet, and tetanus is easily brought on by touch, while spontaneous movements are very labored or quite impossible. This convulsive stage, which may last for hours and days, is decidedly to be regarded as of a reflex char- acter, dependent on increased excitability of the spinal marrow. Thus delirium, hallucinations, etc., are accounted for. A few words must be said as to the influence of atropine on the organs composed of unstriped muscle, v. Bezold and Bloe- baum found in atropinized animals the intestine in complete repose, and even after section of the splanchnic no movements set in. From this they conclude that the motor nerves of the intestine are paralyzed; in the next place the poison paralyzes the intramuscular ganglionic cells, and later the muscular fibres themselves, this paralysis being transmitted to these muscles just as the paralysis of a motor ganglionic cell of the spinal marrow extends to the corresponding muscles. When Keuchel administered small quantities of atropine, the peristaltic action of the intestine did not cease, but the existing movements could not be arrested by irritating the splanchnic; hence he concludes that it exerts a paralyzing influence on the nerve which checks the movement of the intestine and its peripheral extremities. The discovery of the paralysis of the detrusor vesicae urinariae, after previous violent irritation, is the result of clinical observa- tion, not of experiment. Results of Autopsies. Frequent as poisonings by atropine are, very few post-mortem examinations are on record. 1 Trans, of the Royal Society of Edinburgh. XXV. p. 449; and Journ of Anat. and Physiol. 18G9. May. 357. 678 VON BOECK.—VEGETABLE POISONS. Most of the reports of autopsies which we possess refer to per- sons who have died of eating belladonna berries or stramonium seeds. In these cases the stomach and intestinal mucous mem- brane are usually stained with the color of the berries, or else seeds of the thornapple or of the deadly nightshade are found in the intestinal canal. This is pretty nearly the most important result of these examinations. Most of the other results that have been published are by no means characteristic: thinness and fluidity of the blood, which Seaton' mentions, injection of the skin of the face, engorgement of the blood-vessels of the brain and its membranes, an excessive quantity of fluid in the ventricles, some fluid in the pericardium, more or less hyperaemia of the lungs, liver, kidneys, etc. These results are too general to furnish satisfactory evidence in a court of justice. Kuerner2 reports that he performed a post-mortem examination on a boy three years of age, and found that the vagus nerve had a strikingly red appearance in comparison with the phrenic nerve. It is self-evident that such a discovery is of no importance, as it may be merely accidental. Then he found thin fluid blood in the auricles, while the ventricles of the heart were empty. Otto 8 observed marked hyperaemia of the cerebral sinus, of the pia mater, of the medulla oblongata, as well as ecchymoses on the pericardium. Bauer4 lays stress upon the strikingly rapid occurrence of putrefaction. The greatly dilated pupils observed in life generally continue after death. It is clear, then, that we cannot establish the existence of poisoning by atropine simply from post-mortem examinations. Diagnosis and Differential Diagnosis. Atropine-poisoning is recognized by a state of intoxication, accompanied with delirium and dilatation of both pupils. Atropine-poisoning might possibly be confounded with ordi- nary alcoholic poisoning ; but the history of the case, the absence 1 Med. Times and Gaz. Dec. 3, 1869. 2 Vergiftungen durch Beeren der Tollkirsche. Wurtemberg. Corr.-Bl. 1856 No 35 3 Vierteljahrscbrift fiir gerichtliche Medicin. N. F. V. 1. p. 154 1866 4 Wurtemberg. Med. Corr.-Blatt. 1873. p. 113. No. 75. ATROPINE. 679 of alcoholic odor, and the dilatation of the pupils, are sufficient indications to the contrary. Again, it might be mistaken for those affections of the brain which are associated with increase of intracranial pressure, therefore with simple congestion or with apoplexy. The absence of any affection of the arteries, the state of the pupils, the dryness and redness of the mucous membrane of the mouth, the quick breathing, may serve to elucidate the case. Atropine-poisoning has very often been mistaken for cerebral disease,' therefore the chief stress is to be laid on the condition of the pupils. Taking the temperature of the patient will be a sufficient safe- guard against mistaking it for scarlet fever. It is more difficult to distinguish atropine intoxication from that produced by other narcotics ; the diagnosis also becomes difficult if atropine has been applied to the eyes before the poisoning. Sidney Ringer2 men- tions a case in which it was for a long time impossible to diag- nose atropine-poisoning in a woman, who had previously been operated upon for cataract. The surest test of atropine-poisoning is when the unaltered urine acts mydriatically upon the cat's eye. That takes place when the urine contains one part of atropine in 130,000 parts (de Ruiter and Donders). Of course, in diagnosing atropine-poisoning, we must ascer- tain whether atropine has been previously used medicinally. A frequent and most practical method of establishing our diagnosis is to inspect the matters vomited or discharged by the bowels, amongst which we may often discern the skins of the berries, or the seeds that have been eaten. Prognosis. The prognosis of atropine-poisoning must be determined chiefly by the quantity of the alkaloid taken, but still more by the quantity of the poison actually absorbed. 1 Gosset Brown, Lond. Hosp. Rev. II. p. 169.— Morgan, Brit. Med. Journ. Dec. 1, 1866. 2 The Accidental Poisoning of Dr. Sharpey. Lancet. Sept. 27. p. 469. 1873. 6S0 VON BOECK.—VEGETABLE POISONS. If vomiting comes on in the early stage, it is in favor of the patient; diarrhoea may also act favorably. During the course of the case, we must rely chiefly on the condition of the respiration and circulation. In general, the prognosis is not very unfavorable, since recov- ery has occurred even after very large doses, and since, notwith- standing the most dangerous symptoms, a happy result is by no means uncommon. Treatment. If the poison has been introduced by way of the stomach, the stomach-pump and emetics must be used, in order, if possible, to remove the poison before its absorption. Aperients are also advisable to remove any berries, seeds, etc., that may possibly remain in the intestinal canal. In the second place, the poison itself must be, if possible, neutralized. According to Sinogowitz,1 iodine is the best antidote, because iodine gives in solutions of atropine a thick, reddish precipitate ; but Morel2 recommends tannin, and reports three cases which were cured by it. Tannin throws down a white flaky precipitate in atropine solutions, on the addition of a little acid. Garrod3 speaks of two persons who had been poisoned by taking, the one, nine grains, and the other two and a half drachms of belladonna leaves, and whom he cured with animal charcoal; this is supposed to counteract the effect of infusion of bella- donna. Thompson4 recommends solution of caustic potash, to be given every two hours in milk, and says that this will destroy the alkaloid, and speedily remove the symptoms of poisoning. It is certain that alkalies decompose atropine outside the body. Tannin and animal charcoal are decidedly the best remedies as they are innocuous in themselves, and the first at least is read- ily procurable everywhere. 1 Med. Zeit. des Vereins in Preussen. 1854. p. 70. 2 Trois cas d'empoisonnement par la Belladonne. Annal. d. Societe de med de Gand. Sep. 1872. p. 181. 3 Bull, de Therapie. LIV. Fev. 1858. p. 168. 4 Lancet. 1859. Dec. ATROPINE. 681 If the poison has entered into the fluids of the body, the func- tional antidotes have to be considered. C. M. Stevens' reports the case of a woman, twenty-eight years of age, successfully treated by opium and veratrine. When these two drugs are given together it is impossible to determine the influence of the veratrine. Wre can scarcely believe, a priori, that veratrine ex- erts a special influence upon the action of atropine, even though we must acknowledge that the effect of veratrine is to lower the action of the heart. We ought apparently to attach more value to preparations of the calabar bean as antidotes. Frazer,2 for example, reports that dogs, to which he gave a large quantity of calabar, bore it very well when it was administered in combina- tion with atropine; one dog survived the administration of 8 grs. (=0.5) of atropine and 6 grs. (=0.36) of extract of physostigma. Similar results are reported by Bartholow.3 Lorentenz4 gives the case of two women who had taken a considerable quantity of atropine (in one case three-quarters of a grain), and who re- covered very rapidly after he had given them two doses of 25 drops each of calabar tincture, and 3 and 5 drops respectively of a solution of calabar extract in glycerine (1 : 2). In fact, the calabar bean, by virtue of the alkaloid physostig- mine or eserine, which is its active principle, gives rise to a series of phenomena which appear to counteract the effect of atropine. Calabar promotes the flow of saliva, causes contraction of the pupils through spasm of the oculomotorius, sets up spasm and contraction of the vessels, and retards the cardiac pulsation and the respiratory action (see Calabar-Poisoning), v. Bezold and Goetz,6 and subsequently Arnstein and Saststschinsky,8 found that the active principle of the calabar bean retarded the pulse by irritation of the vagus ; they found also that in mammalia 1 Boston Med. and Surg. Journ. Aug. 10, 1871. p. 81. 5 The Practitioner. IV. 67. 1870. 'Ibidem. V. 25. 1870. 4 Hospit. Tijdschr. XIII. 129. und Nord. med. Ark. III. 5. p. 58. 1870. 5 Ueber einige physiologische Wirkangen des Calabargiftes. Centralbl. f. d. med. Wiss. 1867. No. 16. 6 Ueber die Wirkung des Calabar auf die hemmenden und beschleunigenden Herz- nerven. Centralblatt f. d. med. Wiss. 1867. No. 40. 682 VON BOECK.—VEGETABLE POISONS. calabar counteracted the effect of atropine. On the other hand, Boehm ! considers physostigmine, as well as atropine, to be one of the poisons which paralyze the extremities of the vagus; others—B. Tachau ' and Roeber,' for example—attribute the re- tardation of the cardiac pulsation to paralysis of the motor car- diac ganglia, etc. Thus, at present, the most contradictory views as to the action of this poison exist, so that, from theoretical grounds, the value of physostigmine in cases of atropine-poison- ing seems to be, as yet, doubtful. This view is strengthened by the researches of Rossbach and Froelich,4 who maintain that physostigmine does not counteract the influence of atropine upon the heart (but has, to some extent, just the contrary effect), and they did not succeed in producing contraction of the pupils by applying physostigmine to an atropinized eye. Thus no positive results have been arrived at in the human subject, and it remains to be seen whether future investigation will furnish clearer evi- dence. We must not omit to notice Preyer's 5 recommendation of prussic acid as an antidote to atropine. The chief effect of prussic acid, as is well known, is to paralyze the respiratory cen- tre and to stimulate the vagus; therefore it would appear, a pri- ori, to be likely to exert an influence on atropine-poisoning. But this antagonism is denied by Keen and Hare6), as it had been before by Lecorche and Meuriot.7 Preyer's theory has also been disputed from the experimental point of view by Bartholow9, Schroff, jun.,' Knie, and Boehm.10 But, on the other hand, Preyer u 1 Studien iiber Herzgifte. 1871. p. 80 ff. 8 Versuche iib. d. Wirkung d. Calabarbohnenextractes. Heilk. 1865. pp. 69-78. 3 Ueber die Wirkungen des Calabarextractes auf Herz und Riickenmark. Diss. Ber- lin. 1868. 4 Pharmacolog. Untersuchungen. 1 Heft. Wiirzburg. 1873. p. 77. 6 Die Blausiiure physiologisch untersucht. 1868 u. 70. 6 Amer. Jour, of Med. Science. Oct. 1870. p. 442. 1 Etude physiolog. et therap. sur l'acid cyanhydrique. Archiv. gener. de med Paris 1868. Vol. 1. pp. 529 551. 8 Note on Atropia and its Physiological Antagonists. The Practitioner London July, 1870. 9 Medic. Jahrbucher. Jahrg. 1872. pp. 420-513. 10 Knie, Respirationsgifte I. Atropin, Blausiiure. Dissert. Nov. 1873. Dorpat; and Boehm, Archiv fur experimentelle Pathologie u. PharmakoWie II Bd r»n'l20- 148. 1874. ° ' ' PP" 11 Ueber den Antagonismus der Blausaure und des Atropins Ebenda TTT ha ™ 381-396. 1875. " a" PP- ATROPINE. 683 has quite recently repeated his assertion, and supported it by experiments. He has shown that guinea-pigs and rabbits, after subcutaneous injection of watery solution of atropine (two and two-thirds fluidrachms of a five-grain atropine solution), may have deadly prussic acid administered to them without succumb- ing, and that with still larger doses of prussic acid, the action of the poison is protracted if atropine is given. We have not as yet made any practical use of this antagonism of prussic acid in the medical treatment of atropine-poisoning, nor shall we be likely to do so since prussic acid is itself so poisonous an agent. On the other hand, atropine may more safely be recommended as an antidote to prussic acid, and Preyer's researches tend mainly to this end. The treatment of atropine-poisoning by morphine and opiates is of much greater practical importance. Attention has recently been called to this antagonism, and chiefly by the reports of Thomas Anderson,' who cured a case of opium-poisoning, in a man suffering from delirium tremens, by belladonna. His breath- ing gradually became more normal, etc. Since then both poisons have been reciprocally examined, both therapeutically and phy- siologically, but the results of the two methods have not harmo- nized. While, on the one hand, almost all the practitioners who have had the opportunity of testing the antagonistic properties of both poisons, agree, with hardly a dissentient voice, as to their real antagonism, the theorists, on the other hand, basing their opinions upon experiments on animals and upon ratiocination, have come to a totally different conclusion. The chief ground of this difference lies partly in the varying degrees of susceptibility in the animals subjected to experiment—for rabbits, dogs, cats, and pigeons are not equally, sometimes not at all, affected by the same poisons—and in part it lies in the different conception of what is meant by antagonism. Whereas practitioners in general regard the preservation of life after fatal doses as the true cri- terion of an antidote, most pharmacologists claim from an anti- dote that it shall affect the same organs in a directly opposite sense to that of its antagonist. They require, for example, that 1 On the Influence of Belladonna Counteracting the Poisonous Effects of Opium. Monthly Journ. April, 1854. p. 377. 684 VON BOECK.—VEGETABLE POISONS. morphine shall paralyze the very same nervous apparatus which atropine excites, and vice versa, so that, with accurate dosing, the effect of both poisons must be nil. To others it does not matter how the antidote works, provided only that the general effect upon the organ is contrary to that of the first poison. With regard to morphine and atropinel a real antagonism probably only exists betAveen them in respect to their influence on respira- tion ; with regard to the pupil, the antagonism is only functional, because the two poisons appear to affect quite different nerve- elements. That morphine, cautiously used, does good in atropine-poi- soning, cannot, I think, be denied in the face of existing evidence, however sceptically disposed we may be on the subject. Thus Frommhold * has collected eighteen cases of belladonna-poison- ing, which took a favorable course under the opium treatment. And since that time numerous cases in confirmation of this vieAv have been recorded in medical journals. Almost all authorities agree that the most important condition of rapid recovery is the occurrence of quiet sleep, to interrupt the jactitation and deli- rium caused by atropine ; in some few cases the administration of morphine has been followed by contraction of the mydriatic pupils,3 and rapid relief has been afforded to the distressing ischuria.4 Retardation of the pulse is also pretty generally noted, as in the case mentioned by Kohn and Koerner,5 in which the pulse fell from 140 to 100, five minutes after subcutaneous injection of morphine. The frequency of the respiratory move- ments is also considerably diminished ; Agnew6 gives a case in 1 See the subject of Morphine Poisoning. 8 Ueber den Antagonismus zwischen Opium u. Belladonna. Leipzig. 1869. pp. 13-18. 3 For example, Carroll Lee, Americ. Journ. of Med. Science. Vol. 85. 1862. p. 57. In the case of a child six years of age, who had been poisoned with a drachm of suc- cus belladonnae, twenty drops of laudanum were given through the mouth and an equal quantity per anum; after the third dose contraction of the pupil ensued and after 120 drops complete recovery. Bathurst Woodman (Med. Times and Gaz. Oct 8 1864. p. 385) mentions a case, in which the pupils contracted under opium but after- wards dilated again. 4 v. Graefe, Arch. f. Ophthalmolog. IX. 2. p. 71. 1863. b Berlin, klin. Wochenschr. II. 16. 1865. 6 Pennsylvania Hosp. Rep. 1. p. 356. 1868. ATROPINE. 685 which it sank from 30 to 19 in a minute. The difficulty in swal- lowing is also very much relieved. When the dose of atropine has been large, its effect will survive those of moderate doses of opium or morphine, so that when the opiate action ceases, the influence of the atropine again becomes manifest, and repeated doses of morphine, coup sur coup, may be necessary. In such a case, described by Abeille,1 a boy six and a half years of age, who had taken three-quarters of a grain of atropine by mistake, and was found in profound stupor by the doctor, recovered slowly but completely by the gradual injection of morphine. But, however highly we may estimate the value of opiates in atropine-poisoning, we must not forget that the most serious cases of poisoning have been cured even without morphine, and that excessive doses of the antidote will of course act deleteri- ously ; lastly, it must be stated that morphine is not capable of averting death when very large doses of atropine have been taken. We have yet to mention alcohol as a very common remedy in atropine-poisoning ; Holthouse2 gives a case in which it cured a child four years of age, who had been poisoned with from 3 to 4 grs. of atropine. That alcohol may be well borne in atropine-poisoning is proved by a case given by Castaidi,'3 in which a child six and a half months old took eleven and a half ounces of wine and recovered from poisoning, though opistho tonus had set in. It is needless to add that other remedies may be used according to the nature of the symptoms, such as the application of cold compresses to the head, cold douches, arti- ficial respiration, alone or combined with electricity. Ambula- tory treatment may be indicated by symptoms of sopor; it had a very favorable effect in a case mentioned by W. Legg4—Par- sons5 gives a similar case. Bleeding, which has been recommended in various quarters, should be very rarely resorted to. 1 Gaz. med. de Paris No. 43. Oct. 24, 1868. 3 Med. Times and Gaz. Dec. 1859. » Gaz. med. d'Orient. IV. 5. 1860. 4 Med. Times. Nov. 1866. p. 473. 5 A Case of Belladonna Poisoning. Boston Med. and Surg. Journ. June 13, 1872. 686 VON BOECK.—VEGETABLE POISONS. Changes which Atropine undergoes in the Bodies of Men and Animals. Atropine is very rapidly and completely absorbed by the mucous membrane of the stomach, so that in a few hours no alkaloid is to be found in this organ. Absorption by the small intestine is also very complete, yet most of the alkaloid rela- tively is found in it, since it is immediately secreted with the bile into the small intestine again, where it is again absorbed, so that no atropine or at most mere traces of it are found in the freces. But absorption also takes place by the skin and conjunctiva. The atropine dropped upon the conjunctival membrane makes its way into the interior of the eye, and may be detected in the aqueous humor.1 However quickly the poison passes into the blood, it is again very quickly and in an unchanged form se- creted from it, especially by the urine. Thus Meuriot,2 three hours after a small quantity of atropine had been given, found that all traces of it had disappeared from the urine. Schmidt3 found no atropine remaining in the urine after ten hours, though one-fifth of a grain of atropine had been taken. Its entrance into the blood is, of course, most rapid in subcutaneous injection; dilatation of the pupil to its maximum was observed by Schmidt an hour after its internal administration, and by Taylor * fifteen minutes after, while Orfila observed the same effect within twelve minutes of its endermic administration. Atropine has been dis- covered unchanged in various organs of the body,5 muscle, liver, blood, etc. Tests for Atropine. Strictly speaking, the only certain evidence we can have of the presence of atropine in organic substances (as, e. g., matter 1 de Ruyter, Onderzoekingen, etc. Utrecht. 1853-54. VI. ; and Lemattre Arch. general. Juill. Aout. p. 39 et seq 1865. ! De la methode physiologique et de ses applicat. etc. Paris. 1868. 8 Klin. Monatsschrift f. Augenheilkunde von Zehnder. 1864. p. 158. 4 Treatise on Poisons, Deutsche Uebersetzung von Seydeler. s Puczniewsky, De venenis praesertim Cantharidino, Strychnino, Atropino post intox- icationes in sanguine reperiendis. Dorpat. 1858; andBragendorff, Ermittelung der Gifte und Beitriige u. s. w. ATROPINE. 687 vomited, the blood, the contents of the stomach and intestines) is the extraction from them of a substance (not necessarily crys- talline) which can be applied to the eye of the cat, and which produces upon it decidedly mydriatic effects. Very small quan- tities are sufficient for that purpose, whereas dogs, rabbits, etc., require much larger doses. This so-called physiological proof can, however, only establish.beyond all doubt the existence of a mydriatic effect, while its more special characters cannot be determined. The examination of urine is of the highest impor- tance in the recognition of atropine-poisoning. Allan,1 Colin, and Koerner,2 found atropine in human urine, so did Harley3 after the administration of fo of a grain. In many cases it is sufficient to instil the urine unaltered, in others it must be concentrated; but, for perfect security, the short and reliable method of Dragendorff4 should be adopted. The urine is first acidulated with sulphuric acid, then immediately shaken twice with amylic alcohol, and then twice with ether; after the ad- dition of ammonia to the fluid thus purified, the atropine can be immediately dissolved in ether, which, when evaporated, leaves the alkaloid behind in a condition in which it can be easily recognized. The separation of atropine from organic substances is accom- plished either according to the method of Stas and Otto, or according to that of Dragendorff. We digest the substances for several hours in water acidulated with sulphuric acid, then par- tially neutralize with magnesia, taking care that the fluid still remains distinctly acid; we next evaporate the fluid and digest for a long time in alcohol, acidulated with sulphuric acid, then distil off the ammonia and agitate with amylic alcohol, remove the alkaloid by means of acidulated water, again precipitate and dissolve it in fresh ether, or, better still, in chloroform. This generally leaves the atropine behind in a crystalline form. The residual product shows itself to be atropine by a series of reac- tions by no means very characteristic. The most valuable are 1 Annal. der Chemie u. Physik. Bd. 84. p. 223. * Berlin klin. Wochenschr. 1865. p. 162. 8 Brit. Med. Journ. 1868. 28. March und 4. April. « Beitrage zur gerichtl. Chemie einzelner orgaa. Gifte. 1872. St. Petersburg, p. 227. 688 VON BOECK.—VEGETABLE POISONS. the precipitates obtained by potassium-bismuth iodide and po- tassium-mercuric iodide, which, even when greatly diluted, will detect 1 : 4000. * APPENDIX. Poisoning with Hyoscyamus and Hyoscyamine. Hyoscyamine (015H„NO?) is found most abundantly in the seeds of Hyoscyamus niger and Hyoscyamus albus ; it was first obtained in a state of purity in 1833 by Geiger and Hesse ; ac- cording to their accounts it crystallizes slowly in stellate or fas- ciculate masses of silky and, for the most part, transparent aci- cular crystals; it is free from odor, but has a very sharp and unpleasant taste. In the impure state it forms a tough, viscid brown substance, having a heavy, tobacco-like odor. Hyos- cyamine is a true alkaloid, and forms, in combination with acids, salts which crystallize readily. Poisoning has been frequently produced by mistaking hyos- cyamus root for edible roots,2 by taking medicines internally which were intended for outward application,3 by taking over- doses of medicinal preparations,4 and especially by eating hen- bane seeds.5 The symptoms so entirely correspond in every respect with those of atropine-poisoning, that we might consider both forms 1 For further particulars about precautions and methods of separating atropine from organized substances and other reactions, see : Bragendorff, Ermittelung der Gifte. p. 278 ff. 27 These results seem to show that strychnine primarily produces spasm of the glottis in horses, and that the general convulsions which follow upon these are induced by carbonic acid poisoning. But this is not the case in the human subject, therefore tracheotomy may be left out of consideration in general, especially as we pos- 1 Ueber das Gegengift des Strychnins. Med. Zeitg. des Vereins in Preussen. No. 36. p. 178. 1854. 806 VON BOECK.—VEGETABLE POISONS. sess in chloroform and chloral remedies which rapidly produce relaxation of the muscles of the glottis. It is needless to add that the symptoms may sometimes indicate the application of other remedies, e. g., stimulants, etc. Changes which Strychnine Undergoes in the Organism. Strychnine is absorbed by all the mucous membranes, even by the conjunctiva, and passes thence into the blood ; similarly it is absorbed by the subcutaneous tissue ; and it appears from the researches of Leube, confirmed by Jochelsohn, that it is absorbed more rapidly from the intestinal canal than from the subcutaneous tissue. It circulates in the blood, and thus reaches the different organs upon which it exerts its specific action. The next question is, What becomes of strychnine in the organism ; does it leave the body again, unaltered, by the excretions or secretions ? or does it undergo changes in the organism, so that it is either wholly or partially destroyed ? For a long time it was supposed that the poison underwent decomposition, chiefly because attempts to detect it in the urine often failed, and the blood also yielded for the most part negative results. It was concluded that oxygen was the agent which caused its decompo- sition, and that the favorable action of artificial respiration might be referred to decomposition of the poison by the oxygen thus introduced into the blood ; while, on the other hand, if there was a lack of oxygen in the blood, induced by tetanus of the respira- tory muscles, it was believed that the poison escaped decompo- sition, and so worked its evil effects. All these hypotheses are now rendered groundless, as we have absolute proof that strych- nine is excreted from the body unchanged in the urine. Dragen- dorff l and his pupil Masing2 have the merit of establishing this fact. They detected the poison in the blood, though it seems to be present and detectable only in very small quantities; they also 1 Pharmaz Zeitschr. f. Russland. Mai. p. 320. 1867; und Beitrage zur gerichtl. Chemie einzelner organischer Gifte. St. Petersburg. 1872. pp. 185-202. * Beitrage fiir den gerichtl.-chem. Nachvveis des Strychnins und Veratrins Diss. Dorpat. 1868. STRYCHNINE. 807 found it in the bile, in the liver, in the kidneys, etc., but never in the brain. They found most strychnine in the liver, absolutely and relatively, whence they concluded that the poison lingered in the liver. When the poison had been taken by mouth, these authors found it long after in the stomach, and even after repeated vomiting; they also found it in the upper part of the small intestine. They never found it in the faeces, nor in the walls of the great vessels. They did not find the poison in the urine in cases which ran a very rapid course, either because the poison is contained in too small quantities in the urine, or perhaps because, through the general vascular contraction caused by strychnine, the secretion of urine takes place more slowly than usual. Generally the excretion of strychnine in the urine appears to be a somewhat slow process. When Dragendorff and Masing introduced doses of a few milligrammes into a dog for several consecutive days, they found no strychnine in the urine till about the third or fourth day; but the excretion of the poison continued some days after the administration had ceased. This illustrates the cumulative action of the poison. The fact that strychnine was found in the bile, but not in the lower part of the intestine, leads to the conclusion that it must have been reabsorbed. Gay,1 under Danilewski at Kasan, has proved experimentally that strychnine is also excreted through the saliva. The length of time during which the poison can be detected in the stomach may, partially at least, depend on the saliva swallowed. Dra- gendorff 2 has stated emphatically that in the numerous experi- ments he has performed "it has certainly not been proved that conditions exist in the blood which can determine the decompo- sition of strychnine." Chemical and Physiological Tests. In a case of strychnine-poisoning we should especially en- deavor to recognize the poison in the matters vomited, and when 1 Centralblatt f. d. med. Wissenschaften. No. 4. p. 49. 1867. * Beitrage, etc. p. 196. 808 VON BOECK.—VEGETABLE POISONS. the case has been protracted, in the urine. If an autopsy is per- formed, the most important organs are the stomach, the liver, with the gall-bladder and bile, the kidneys, the blood, the upper part of the small intestine. Strychnine has fairly characteristic reactions. We should use for the purpose of testing—according to Otto—a solution of strychnine in concentrated cold sulphuric acid, which solution is colorless. If we introduce into this solu- tion, conveniently placed in a small watch-glass, a crystal of potassium bichromate as large as a pin's head, and agitate the fiuid by inclining the watch-glass to one side and the other, violet streaks appear, changing to blue, so that finally the whole fluid becomes violet or, with large quantities of strychnine, blue; but this color lasts only a short time; soon it passes into red, and then into a dirty-green. According to Otto, if by evaporation we obtain a residuum of strychnine on a watch-glass, we should moisten it with a solution of potassium bichromate, then quickly pour off the fluid, or absorb it with filtering-paper, and next drop some concentrated sulphuric acid on the residuum, when the blue color immediately appears. If we have enough strychnine, we may dissolve it in water charged with sulphuric acid, and add to it a solution of potassium bichromate, upon which yellow crystals of chromate of strychnine are formed, which dissolve in concentrated sulphuric acid with a blue color. A similar result is obtained by adding a small crystal of red prussiate of potash (Davy), especially if some nitric acid is added to the strychnine solution ; it is also obtained by crystals of potassium hyperman- ganate, by potassium chromate or iodate, by hyperoxide of lead (Marchand) or manganese (J. Erdmann), etc. Otto's reaction is capable of giving positive results even with one-sixty-thousandth of a grain (= 0.000001) of strychnine, as de Yrij and von der Burg1 have shown. Husemann's admirable work, " Die Pflanzen- stoffe," gives full details of a whole series of other reactions (p. 387 ff.). The separation of strychnine from organic substances is best accomplished by Uslar and Erdmann's method, modified by Dra- gendorff ; the residuum, extracted by water acidulated with sul- 1 Annales d'Hygiene. Avril, 1857. STRYCHNINE. 809 phuric acid and then dried, must be treated with benzine or chloroform, which fluids extract the alkaloid from the residuum, and, on evaporation, deposit it on a watch-glass, where it can then be tested according to the method given above. The microsubli- mation of Helwigl may also be used as a test; it does not, how- ever, yield more accurate results than the chemical test. Apart from the chemical test, the physiological test may also be of some value. This consists in introducing into the body of a frog some of the residuum obtained by the process given above; if the residuum contains strychnine, the frog is seized with tetanus. This so-called physiological test must, however, be often re- peated in order to obtain an absolutely certain conclusion ; care must also be taken to exclude the presence of other substances which cause tetanus, e. g., picrotoxin, nitro-glycerine, brucine, and even caffeine, which, according to Schmiedeberg,2 produces tetanus in rana esculenta. The fact deserves mention that strychnine resists decomposi- tion for a long time, as appears from the experiments of Dr. Majer3 and Riekher.4 According to the latter, it may be de- tected by testing even after eleven years. Although Majer holds the test for strychnine to be one of the most certain, yet it has failed in many celebrated trials; thus in Palmer's case strych- nine was sought for in vain ; neither was it found in the Demme- Truempy case. This circumstance has contributed greatly in its time to confirm the hypothesis that the poison is decomposed in the body, or that it enters into combination with albuminous substances, etc.* The reason why strychnine cannot always be detected is due mainly to the fact that testing for it requires great and constant practice ; for Dragendorff himself states, in 1 Das Mikroscop in der Toxikologie. Mainz. 1865. contains an atlas of photographed microscopic preparations, which show the sublimated poisons per se, and treated with different reagents, in their characteristic peculiarities. Dr. Erhard follows in the same direction, " Die giftigen Pflanzenalkaloide uDd deren Ausmittelung auf mikroscopischem Wege." Passau. 1866. 2 Ueber die Verschiedenheit der Caffeinwirkung an Rana temporaria und Rana escu- lenta. Archiv f. exp. Patholog. u. Pharmacolog. II. Bd. pp. 62-70. 3 Wiirtembergisch. arztl. Corresp. -Blatt. 25. 1857. 4 Neue Jahrbiicher f. Pharmaz. Bd. 29. 1. 1868. 6 See Cloetta. Virchow's Archiv f. path. Anat. Bd. XXXV. p. 369. 810 VON BOECK.—VEGETABLE POISONS. his "Beitrage," that his pupils at first were not experienced enough to detect the poison in the blood, which he himself suc- ceeded in doing with certainty. APPENDIX. Poisoning with Brucine. Brucine (€MH9,Na04) is constantly found accompanying strych- nine in the plants which contain it, and its action, so far as is known, is completely analogous to that of strychnine, only some- what weaker. In all cases of poisoning, therefore, by nux vomica, false angustura, etc., a part of the action is traceable to brucine. There are no instances of primary brucine-poisoning, so far as my knowledge goes. Poisoning with Picrotoxin. Picrotoxin is a strong poison, which is found chiefly in the Cocculus indicus ; its formula is 012H140&; it was first discovered by Boullay in the fruit of the Anamirta cocculus ; it consists of colorless, glossy, acicular crystals, generally in stellar, more rarely in foliaceous groups. It is free from odor, but has a very bitter taste ; its reaction is neutral; it is soluble in 150 parts of cold and in about 25 parts of warm water ; is readily soluble in warm alcohol, sparingty so in ether. It is also soluble in chloro- form and amylic alcohol. Etiology. Poisoning by picrotoxin occurs when either picrotoxin itself in quantities of about a gramme (fifteen grains), or a correspond- ing quantity of Cocculus indicus is introduced into the system. Vossler x killed a cat in two hours by administering two grains 1 i). Tschudi, Die Kokkelskorner und das Pikrotoxin. St. Gallen. 1847. PICROTOXIN. 811 (0.12) internally; while a dog was violently poisoned, but not fatally, by the same quantity. Picrotoxin has been, of late years, frequently added to beer, especially in England, to increase its strength ; Cocculus indicus is also used in baiting fish ; it is sometimes used medicinally, and may thus lead to poisoning. Pathology. Symptomatology and Course. Poisoning by picrotoxin is of rare occurrence in human be- ings, and we have no records of cases ending fatally. The symptoms produced in the human subject by three grains (0.2 gramme), are nausea, vomiting, muscular debility, somnolence, and sometimes convulsions. The action of the poison on animals is better known ; thus Falck's' researches show that fish become very restless, weak, and die from asphyxia; frogs exhibit extensor convulsions and disturbed respiration, with diminution of cardiac pulsations ; in doves, in addition, there is trembling of the limbs and circular movements, with convulsions and increased flow of saliva ; in cats also there is increased secretion of saliva, convul- sions, and they ultimately become paralyzed ; similar symptoms occur in dogs, with loud whining and scratching with the feet. Analysis of Symptoms—Mode of Action of Picrotoxin. To Roeber2 belongs the chief credit of ascertaining the action of this poison. According to him, it gives rise to convulsions which, in contradistinction to those caused by strychnine, are not of a reflex nature. These convulsions assume the most various forms, and resemble compulsory movements. The pul- monary portion of the vagus is excited, hence the accelerated respiration and the strong inspiratory dilatation of the thorax; the cause of this last symptom is that the expulsion of the in- 1 Beitrage zur Kenntniss des Pikrotoxins. Deutsche Klinik. Nos. 47-52. 1853. 2 Ueber die physiologische Wirkung des Pikrotoxins. Arch. f. Physiologie. p. 30. 1869. 812 VON BOECK.—VEGETABLE POISONS. spired air is impeded by spasm of the glottis. If the vagus is divided beforehand this symptom is absent. During the attacks reflex excitability is suspended, but it returns afterwards. Car- diac contractions are greatly retarded, the heart is very much relaxed and dilated. After destruction of the brain the symp- toms are essentially the same ; after destruction of the lobi optici the convulsions set in less violently ; after destruction of the medulla oblongata the tetanus ceases, and we get only a coma- tose condition. Hence Roeber concludes that picrotoxin irri- tates the ganglia and the medulla oblongata, and that the motor centres, the vagus centres, and Setschenow's reflex inhibitory centre, are chiefly affected. Its influence on the heart depends partly on central irritation of the vagus, but is partly due also to excitement of the cardiac centres themselves. Diagnosis and Differential Diagnosis. In the case of the human subject the diagnosis rests mainly on the presence of convulsions, with accelerated respiration and retarded cardiac contraction. A superficial observer may mis- take poisoning by picrotoxin with that by strychnine or bru- cine. This error may be avoided by knowing that sensible impressions do not lead to reflex convulsions in picrotoxin, as in strychnine-poisoning. Prognosis. A favorable prognosis depends on the rapidity with which vomiting sets in. Results of Autopsies. We find no characteristic phenomena in dissecting mammalia which have been poisoned by picrotoxin. Engorgement of the cerebral membranes and of the spinal marrow, of the plexus chorioidei, hyperaemia and oedema of the lungs, rarely pulmo- nary anaemia, emphysema of the lungs, hyperaemia of the liver, etc., a little clotted blood in the heart, etc., are the few positive results. PICROTOXIN. 813 Treatment. The first and most important step in the treatment of picro- toxin-poisoning is the elimination of the poison from the stom ach by means of emetics or the stomach-pump. There are no chemical antidotes, as tannin even does not throw down any pre- cipitate. So long as convulsions are present, narcotics—opium, morphine, hydrate of choral, even chloroform—may be adminis- tered, whereas when paralysis begins, stimulants—wine, alcohol, ether, camphor, etc.—must be employed. Chemical and Physiological Tests. Picrotoxino is soluble in cold concentrated sulphuric acid, yielding a golden yellow, almost saffron color, which changes into violet on the addition of a very small quantity of potassium chromate. If more of this is added the color becomes brown. Picrotoxin mixed with three times as much nitre, and moist- ened with concentrated sulphuric acid, gives, on the addition of strong caustic soda to the residuum, a brick-red color. The usual procedure must be adopted for separating picrotoxino from organic substances, and it can be extracted from acid watery solutions by means of ether or amylic alcohol. Gruenkel1 acidulates with acetic acid, adds alcohol, and ex- tracts with ether, which on evaporation leaves a residuum of pricrotoxin in the form of feathery crystals. It reduces hy- drated oxide of copper and potassium bichromate. The physiological test depends on the action of this poison upon fish. When picrotoxin is added to the water in which they live, they make winding and boring movements of the body, alternating with quiet swimming, open their mouths and gill- covers frequently, fall on their side, and die rapidly of asphyxia. Changes which this Poison undergoes in the Organism. Picrotoxin passes into the blood, evidence of which, accord- ing to Vossler, is afforded by the fact that flies and fleas which 1 Arch, der Pharmaz. CXLIV. Apr. 1858. 814 VON BOECK.—VEGETABLE POISONS. have sucked the blood of animals poisoned by picrotoxin, die immediately. It has not yet been proved that it is excreted unchanged in the urine, though there is a very strong probability that such is the case. Poisoning with Coniine and Plants containing Coniine, especially Con iu m Maculatum. Coniine (C8H15N) is an alkaloid, and in a pure condition is a clear fluid transparent as water, which evaporates at ordinary temperature ; it was discovered by Giesecke as early as 1827, but Geiger was the first to prepare it pure ; in late years Wertheim succeeded in preparing coniine artificially. If the alkaloid is exposed to the air, the fluid becomes at first yellow and then brown, and, finally, of a resinous consistence, while ammonia escapes. Coniine is contained in all parts of the hemlock plant (Conium maculatum), and, as Schroff1 has shown, the alkaloid is most abundant in the seeds of plants two years old, while the leaves at the blossoming time also contain a great deal of the poison. It is sparingly soluble in water, but readily so in alco- hol and ether ; it has a very unpleasant odor, resembling that of tobacco-juice. Etiology. Poisoning by coniine was more frequent in ancient times than now. In ancient Greece, hemlock was very much used for the purpose of murder and suicide, and even for capital punishment; as every one knows, Socrates was condemned to drink the cup of hemlock, when accused of corrupting the minds of the Athe- nian youth and denying the gods. Cases of poisoning by hem- lock do, however, occur in modern times, but they usually arise from mistaking the plant for parsley, parsnip, or chervil, or from confounding the seeds with aniseed; indeed, the two sorts of seed have been mixed together and sold. Medicinal poisonings 1 Wochenblatt der arztl. Gesellschaft zu Wien. CONIINE. 815 are also on record, caused by overdoses of the poison. Bennet * reports a case in which a man, forty-three years of age, died of poisoning, caused by mistaking this plant for some other vege- table. Attilio Bianchi2 describes the poisoning of two children, seven and eight years of age, by eating hemlock-root. A case of murder by this poison also occurred recently. In the year 1861, Dr. H. Jahn, of Dessau, poisoned his mistress, L. B., with coniine. It has been asserted that many animals, e. g., birds, goats, sheep, and even cows, enjoy immunity from the action of the conium plant, while human beings may be poisoned by eating the flesh of these animals. This immunity, however, is not yet satisfac- torily proved. A case of suicide3 by Conium maculatum commit- ted by an American, Dr. Walker, at New York, in the summer of 1875, was reported in most of the German newspapers. It is impossible to state with accuracy what constitutes a fatal dose of this alkaloid or of the parts of the plant containing it. The new German Pharmacopoeia prescribes 0.001 (^- of a grain) per dose, and 0.003 (^\ of a grain) per day, as the maximum dose of coniine, of hemlock leaves 0.3 (four and a half grains) per dose, and 2.0 (thirty grains) per day. So that coniine is among the most energetic poisons with which we are acquainted. Pathology. Symptoms and Course. When coniine or conium is taken, it creates a burning sensa- tion in mouth and throat, and pain in the tonsils, as SchneUer4 found by trying small doses on himself. Neligan * observed also constriction of the gullet and difficulty of swallowing in a pro- 1 Empoisonnement par la cigue. Journ. de Phys. etdeChimie. T. X. p. 123. 1846. ,J Gaz. Lombard. 21. 1857. 3 This case should not be described as "suicide." A preparation of hemlock was prescribed medicinally, and the patient, a great sufferer, took dose after dose in viola- tion of the careful instructions of the prescriber, probably in the vain hope of obtaining the relief which the doses as ordered failed to procure.—E. C. 4 Pharmacologische Studien. Zeitschr. der Wiener Aerzte. Marz. 1846. 6 De l'emploi de la cigue dans les effets douloureuses. Jour, de Phys. et de Chim. T. IX. p. 119. 1846. 816 ON BOECK.—VEGETABLE POISONS. traded case. Increased flow of saliva has been observed1 by SchneUer and Flechner. If coniine has entered the blood in sufficient quantity, the poisonous effect sets in early and with tolerable rapidity. In many cases the poisoned persons fall down suddenly ; soon after this, a marked degree of muscular debility sets in, with dyspncea and marked precordial distress. The respiratory movements become labored and slow ; the pulse is also considerably re- tarded, and paralysis of the voluntary muscles follows. The res- pirations become slower and slower, till after some time they cease altogether, generally in a few minutes or hours, while the cardiac action continues. Consciousness usually remains intact; at the utmost a swimming in the head sets in ; thus it is explica- ble how Socrates could continue his conversation with his friends up to the moment of death. The pupils are constantly dilated, and disturbances of vision are common. In many cases vomit- ing ensues, and towards the close of the case clonic convulsions set in, which are apparently traceable, partially at least, to the accumulation of carbonic acid in the blood in consequence of impeded respiration. In the case of the two children whose poi- soning Bianchi describes, the facial muscles were strongly impli- cated in these convulsions, as well as the extensors of the spine and the flexors of the limbs. If these symptoms continue, the tem- perature of the body becomes much reduced ; the skin becomes pale, and death ensues. If the case takes a favorable turn, the respirations become more frequent, the highly-marked cyanosis diminishes, and the normal condition is gradually restored ; but recovery is very slow, and an intense muscular debility remains behind, which manifests itself chiefly by tremor of the legs. Analysis of Symptoms—Mode of Action of Coniine-Poisoning. The most striking feature in the action of coniine is the mus- cular paralysis it induces, which ultimately extends to the re- spiratory muscles, so that breathing becomes impossible. This muscular paralysis is due to the influence of coniine on the peri- 1 Beitrage zur Physiologie der Arzneiwirkungen. II. Zeitschrift der Wiener Aerzte. Juni. 1847. CONIINE. 817 pheral extremities of the motor nerves, as well as on the motor centres. For when Albers' injected coniine subcutaneously into a frog's leg, it was very soon completely paralyzed, and shortly after the paralysis spread over the whole body. Koelliker,3 who has earned so much distinction by his researches into the physi- ological action of so many poisons, proved that it is the extremi- ties of the motor nerves in the muscles which are paralyzed by coniine in the first instance; the muscles themselves as such remain excitable, unless the poison is directly applied to them, and then, as it excites a local corrosive action, it destroys their power of contracting. It appears from the researches of Damou- rette and Pelvet,3 and of Verigo4 that, besides the peripheral action of coniine, it also acts upon the motor centres. Accord- ing to Guttmann,5 whose statement is entirely confirmed by the researches of Koelliker and Ihmsen,6 the trunks of the nerves are also paralyzed, but at a very late period. The sensory nerves are affected by coniine, though only in a subordinate degree ; this fact is observed and established less by physiological researches than by actual experience in the case of human beings. Thus Guttmann asserts that coniine, applied to the cuticle, renders it anaesthetic ; this is confirmed by the fact that the hands of peo- ple who express hemlock become completely insensitive. Even in ancient times priests7 were recommended to use friction of the hemlock plant in the region of the genitals to enable them the more easily to keep their vows of chastity and continence. The statements of therapeuticians that coniine alleviates the reflex spasm in photophobia,8 and produces a general anaesthetic effect, is consistent with the foregoing.9 1 Ueber die Wirkung des Theins auf das Herz u. die physiol. Wirkungen des Coniins. Deutsche Klinik. No. 34. 1853. 2 Physiologische Untersuchungen iiber die Wirkung einiger Gifte. Virch. Arch. Bd. X. p. 235 ff. 1856. 3 Gaz. med. de Paris. 1870. Nos. 9-37; and Bull, de Therap. 1870. Juin-Decbre. 4 Deutsche Zeitschrift fiir Staatsarzneikunde. XXVIII. 213. 6 Ueber Coniin. Berlin, klin. Wochenschr. Nos. 5, 0, 7, 8. 1866. 6 Disquisitiones physiologo-toxicologicas de Coniino. Dissert. Petersburg. 1857. ' Doellinger, Heidenthum und Judenthum. p. 171. 8 Spengler, Ueber die Wirkung des Coniin. Neue Zeitsch. fiir Med. u. Med. Kef. Bd. I. Hft. 1. 1850. 9 See Neligan, 1. c; Reuling and Salzer, Ueber die Wirkung des Coniins. Deutsche Klinik. No. 41. 1853. VOL. XVII.—52 818 VON BOECK.—VEGETABLE POISONS. Death is sometimes preceded by convulsions ; in frogs they are always absent, in mammalia they are almost constant. These convulsions might be regarded as simple consequences of car- bonic acid poisoning, and certainly a number of them depend on respiratory disturbances ; but Guttmann's experiments make it very probable that these convulsions may be directly caused by the central action of the coniine, as he failed to arrest by artifi- cial respiration the convulsions produced by coniine. The respiratory disturbances, which consist in a remarkable retardation of the respiration, are only the consequence of the action of coniine on the nerves of the muscles. The action of the heart is also affected by this poison, though much more slightly, and it continues to beat to the last. As a general rule, cardiac pulsation is retarded in coniine-poisoning. It would appear from Boehm's' investigations that the cardiac extremities of the vagus are paralyzed by coniine, but not the actual inhibitory centres, the excitability of which remains unaltered. The fall of tem- perature in animals poisoned by coniine depends partly on the action of the poison on the vessels which, according to Gutt- mann, are dilated. Nega2 also speaks of diminished innervation of the vessels caused by coniine. According to the views of Leonidas van Praag3 and Danilewsky4 this poison exerts a pri- mary action upon the brain and spinal marrow, v. Praag attributes death by coniine to paralysis of the spinal marrow. Danilewsky speaks of an initial excitement followed later on by paralysis of the hemispheres and of the reflex apparatus. Thus respiratory paralysis is to be regarded as the main effect of coniine ; this paralysis itself depending on the paralysis of the intramuscular extremities of the motor nerves ; death by coniine is therefore caused by its action on the respiratory organs. 1 Studien uber Herzgifte. p. 88. 1871. 2 Das Coniin als Arzneimittel. Giinsburg's Zeitschr. f. klin. Medic. Bd. I. Hft. 1. 1850. 3 Coniin, Reil's Journal f. Pharmacodynamik, Toxikologie und Therapie. I Hft. p. 1 ff. 1856. 4 Arch. f. Anat. u. Physiol. Hft. 6. 1866. CONIINE. 819 Diagnosis and Differential Diagnosis. Coniine-poisoning may be recognized by the consequent ady- namia, followed by loss of muscular power, together with dysp- ncea, while the cardiac contractions remain comparatively un- affected. The action of this poison has the greatest resemblance to that of curare, only the paralytic symptoms in curare are much more pronounced, while in coniine they are not so fully developed, at least in mammalia. If convulsions come on before death the diagnosis of coniine-poisoning is much more certain; also it may help us if we remember that Conium maculatum grows wild with us, whereas curare is very difficult to procure. The acuteness of the attack, and the fact that all the muscles are equally involved in the paralysis which it occasions, may help us to distinguish this form of poisoning from ordinary diseases of the spinal marrow. The diagnosis may, of course, be aided by the inspection and examination of the vomited matters, since we may find there the remains of parts of the plants which have been eaten, and recognize them by their appearance and odor. Prognosis. The prognosis in coniine-poisoning is necessarily, in the first instance, dependent on the quantity of the poison in operation ; vomiting at an early stage is favorable ; practically the condition of the respiration is of the greatest importance; the less it is impeded the more encouraging the prognosis, and vice versa. Results of Autopsies. When we do not find portions of plants in the stomach which can be certainly recognized as conium (the best test is to develop the unpleasant tobacco-like odor of coniine by reducing the leaves to powder with caustic potash), there are no really char- acteristic phenomena in autopsies after death by this poison. The blood is generally found in a fluid condition, and appears to resist coagulation ; it is red, and becomes redder when exposed 820 VON BOECK.—VEGETABLE POISONS. to the air. Hyperaemia of the brain, and especially of its me- ninges, is said generally to exist. In the lungs, as well as in the great abdominal glands, we find the signs of death from asphyxia, venous hyperaemia, and cedema. When pure coniine has been administered, some redness, etc., is found in the stomach, but when the leaves of the plant have been eaten, green mucus is generally the only thing to be found there. Treatment. The first point in the treatment of coniine-poisoning is to eliminate the poison as rapidly as possible by the use of emetics or the stomach-pump. The second is the application of stimu- lants to the spine to promote respiratory action. Respiratory movements must above all things be kept up, and therefore arti- ficial respiration must in some way or other be maintained. The best therapeutic result may be expected from this, as the action of the heart is comparatively so little affected. Tannin is to be recommended as a so-called chemical antidote; it forms a precip- itate with coniine. Changes which Coniine undergoes in the System. Coniine passes unchanged into the circulation; absorption takes place with tolerable rapidity from the mucous membrane of the stomach and intestine. It is not decomposed in the organ- ism, for it can easily be detected unaltered in the blood, the liver, and the urine, by which it is excreted. The elimination of the unchanged poison in the urine occurs with considerable rapidity, for coniine was found in the urine shortly after its administration by Paul Zalewsky * who, under the direction of Dragendorff, experimented on the detection of coniine in the organism. Chemical Test. The tests given for coniine are by no means characteristic of this poison only. The following process is that given by Dra- 1 Untersuchungen iiber das Coniin in forenser Beziehung. Dorpat. 1869. CYTISINE. 821 gendorff and Zalewsky after many experiments in detecting coniine in organic substances: Reduce the substances to powder, dilute them if necessary, and digest with dilute sulphuric acid (one part to five parts of water) for twenty-four hours, at a temperature of from 95° to 140° Fahr., filter, concentrate the filtrated substance, mix it with three or four times its volume of alcohol, leave it twenty-four hours, and filter. The alcohol is separated from the filtrate by distillation (in a water-bath). After it becomes cold, filter again, shake the filtrate twice with half its volume of benzol, mix with ammonia, shake with one- quarter its volume of petroleum ether, and finally wash with water. The petroleum ether, on evaporation, leaves the alkaloid behind. This is recognized as coniine, first, by the odor, which, however, may be deceptive or disappear ; secondly, and chiefly, by the characteristic crystalline form of coniine hydrochlorate. Pour a few drops of hydrochloric acid on a watch-glass, and add a few cubic centimetres of the petroleum ether extract, and evaporate the mass at from 68° to 86° Fahr.; the residuum is a delicate iridescent film, which, when magnified 100 times, is seen to consist of acicular crystals, hanging together by lateral off- shoots, and mingled with numerous small granular bodies. The crystals produce double refraction of light (Helwig1 has given drawings of these crystals), and have the odor of coniine, which is rendered more intense by breathing upon them. The solution of these crystals in dilute sulphuric acid throws down with potassium-bismuthic iodide an orange-colored precipitate, which is discernible even when diluted one-six-thousandth times. It also throws down a precipitate with molybdo-phosphoric acid. Poisoning with Cytisine and Plants containing it. Cytisus Laburnum. Cytisine (es0H27N"3O) is the alkaloid which was discovered by A. Husemann and Marme, in 1864, in various parts of the Cyti- 1 Das Mikroscop in der Toxikologie. 822 VON BOECK.—VEGETABLE POISONS. sus Laburnum ; it is also found in several other species of Cytisus. It appears as a white, glistening, crystalline substance, which is devoid of odor, but has a bitter and slightly caustic taste;l it has an alkaline reaction, is readily soluble in water and alcohol, but is not soluble in ether or chloroform. Etiology. A considerable number of cases of poisoning by the Cytisus Laburnum have been published. Christison2 relates the poison- ing of a cook, into whose soup a man-servant had thrown a piece of the bark. Sedgwick3 saw two children who were poisoned by chewing the root of the shrub instead of licorice root. Lesage Picon4 saw six persons of one family made ill by eating labur- num blossoms instead of baked acacia blossoms. The seeds of the laburnum are also poisonous, as is proved by the observation of John Popham,5 who saw ten boys who had been made ill by eating them. George. Fischer6 relates that two children, two and a half and four and a half years of age, ate some pods of Cyti- sus Laburnum, and became violently sick. Wilson7 mentions the death of a child who had gnawed at laburnum bark ; the case terminated fatally in eight hours. Dr. Rouge 8 communicates a case in which a company of fourteen persons were poisoned by eating cakes which had been made with laburnum blossoms in- stead of acacia blossoms. Graham9 mentions a case in which sixteen girls, from two to nine years of age, had eaten laburnum seeds. Weelhouse ,0 reports a second case of death : a young girl five and a half years of age ate unripe pods of laburnum, and 1 Husemann und Marme, Zeitschr. f. Chem. 1865. 161. 2 Poisoning with the Bark of Cytisus Laburnum. London Med. Gaz. Oct. 1843. 3 Med. Times and Gaz. Jan. 3, 1857. 4 Rev. therap. du Midi. XIII. p. 396. 1859. 5 Dubl. Med. Journ. Feb. p. 248. 1863. 6 Schuchardt's Zeitschr. fiir prakt. Heilkunde. Hft. 5. p. 408. 1867. ' Lancet. Jan. 18. p. 86. 1869 ; and Pharm. Journ. Feb. 1868. p. 395. 8 Revue med. Tom. 1. 15. Feb. 1868. p. 191. 9 Med. Press and Circul. July 29, 1868. 10 Laburnum-poisoning. Brit. Med. Journ. Jan. 22. p. 79. 1870. CYTISINE. 823 died in nine days of the poisoning. Henry Wilson1 gives a case to prove that even a small number of seeds may produce cytisine- poisoning: a boy four years of age became violently sick after eating ten seeds. The latest reports of cases ending in death were communicated by Hinkeldeyn :3 three children at Liibeck had eaten pods and seeds of laburnum ; two children, each five years of age, fell into convulsions, were seized with violent vom- iting, the matters vomited being mixed with blood, and died in a very short time. A case of medicinal poisoning by a decoction of cytisus blossoms is reported by Pollak,3 in which a girl at Teheran suffering from dropsy, after taking the decoction, was seized with vomiting and diarrhoea, with violent collapse. No cases of poisoning with pure cytisine or its salts have been hitherto observed; it is therefore impossible to state accu- rately what quantities produce poisonous effects. According to Marine's investigations, about half a grain (0.03-0.04) is sufficient to kill cats by subcutaneous injection ; when injected into the blood, from one-sixth to one-fourth of a grain (0.01-0.015) killed large rabbits and cats ; half a grain (0.03) destroyed life in dogs. Symptoms and Course. As a rule, symptoms of poisoning set in very soon after the poisonous constituents of plants have been taken; the nausea and vomiting which precede the other symptoms set in in some cases in a few minutes, whereas in other cases hours may elapse before these symptoms appear; this circumstance most proba- bly depends upon the repletion or emptiness of the stomach. Among the first symptoms are generally headache, giddiness, swimming in the head. Afterwards we often get dryness of the throat, a sensation of heat in the head, and a feeling of great general debility. These symptoms may last a longer or shorter time ; vomiting has sometimes been observed to continue twenty- four hours (Christison). 1 Lancet. Sept. 16. p. 391. 1871. 2 Deutsche klinik. 27. p. 252. 1873. s Wien. med. Presse. 9. 1868. 824 VON BOECK.—VEGETABLE POISONS. Another symptom in most cases is diarrhoea, sometimes of a very persistent character. The vomiting and diarrhoea are gene- rally attended by violent pains in the stomach and intestine. In slighter cases of poisoning, in addition to these symptoms, col- lapse may also be induced, due in part to the acute drain of fluid. In severe cases motorial disturbances occur, convulsive twitchings in the face and limbs, complete incapability of walk- ing, cramps in the muscles of the eyes, etc. The heart-stroke is generally accelerated, and is weaker than in the natural condi- tion ; the respiration is labored and difficult, the temperature reduced ; the patient has an anxious expression ; the pupils are generally dilated; there is great thirst and great restlessness. This jactitation is followed in some cases by a condition of sopor with loss of consciousness, which, however, may return for a while. Death supervenes with the symptoms of asphyxia, either with or without convulsions, and is preceded generally by loss of consciousness (Hinkeldeyn' s case). In Weelhouse' s case death did not supervene till the ninth day after the poisoning, the prostration caused by the vomiting and the persistent dysenteric diarrhoea leading finally to a fatal result. In the one case men- tioned by Hinkeldeyn death occurred through rupture of the stomach in consequence of the vomiting. In a few cases actual hallucinations and delirium have been observed; very many cases are attended with sleeplessness. The debility and this sleeplessness may under some circumstances last a long time; for instance, it lasted for a whole week in the case of a girl, eighteen years of age, communicated by Tinleyx; in Christison's case of the cook who was poisoned, the debility and alternate vomiting and diarrhoea lasted more than six weeks, so that she was obliged to give up her place, and recovered very slowly. But in general convalescence sets in early, and the health is restored to its usual condition in a few hours or days. Analysis of Symptoms—Mode of Action of the Poison. By Christison's suggestion, Dr. Ross, more than thirty years ago, made experiments with Cytisus Laburnum, which showed 1 On a Case of Poisoning by Laburnum. Lancet. Aug. 6, 1870. CYTISINE. 825 that it caused vomiting and diarrhoea in dogs and cats, but in rabbits it caused convulsions, often amounting to tetanus. We are indebted to W. Marmel for a thorough examination of the effects of cytisine. This investigator made experiments on all kinds of animals with nitrate of cytisine, and proved by experi- ment that the poison might be absorbed from all possible points of application. As to the effect of cytisine, he observed chiefly two stages, distinct from one another, that of jactitation and that of depression. At the outset of the case he often observed symp- toms of tetanus ; the spinal marrow and the motor nerves are at first excited, later on paralyzed, and the paralysis begins in the peripheral extremities of the motor nerves. The muscles are also affected, but much more slightly than their nerves ; in this way the disturbances observed in the motor apparatus in human beings are accounted for. The respiration is at first accelerated, then retarded and dyspnceic ; cardiac contraction is accelerated by stimulation of the excito-motor ganglia; the peristaltic con- traction of the intestine is increased, hence the diarrhoea. Con- sciousness seems to remain intact in animals. Results of Autopsies. There are very few published reports of autopsies after cyti- sine-poisoning, and the few which are known contain nothing characteristic of this poison. We should expect from the symp- toms observed in life to find evidence of gastro-enteritis in the intestinal canal. Hinkeldeyn, however, who performed two such autopsies, expressly states that he found no trace of inflamma- tion in the stomach and intestine. In one case this author found perforation of the stomach, as the result of violent vomiting when the stomach was replete. Diagnosis and Differential Diagnosis. The diagnosis of cytisine-poisoning must rest in the first place upon the history of the case, and then upon the examina- 1 Ueber Wirkung u. Vorkommen des Cytisins. Nachrichten der Gottinger Societat der Wissenschaften. p. 24. 1871. 826 VON BOECK.—VEGETABLE POISONS. tion of the vomited matters, which may contain portions of the parts of plants which have been eaten. If these data are absent, it will be very difficult to diagnose the poisoning with certainty, as all the symptoms which are produced by cytisine belong more or less to other poisons, and specially also to emetics. It is pos- sible to mistake its action for that of a so-called drastic emetic, or with acute gastro-intestinal catarrh, or even with arsenical poisoning or cholera. It is worthy of note that poisonings with Cytisus Laburnum occur almost exclusively in summer, when the tree is in blossom, and that in general only children and thought- less young persons are poisoned by it. Prognosis. From what has been said, it follows that death very rarely occurs from cytisine-poisoning, so that the prognosis is generally favorable. This is due to the spontaneous vomiting, by which the greater part of the poisonous matter can be eliminated from the body before absorption. The prognosis will be all the more favorable if but a small quantity of the poison has been swal- lowed, if vomiting sets in rapidly, and if there is not much gas- tric disturbance or collapse. It is also of consequence that a rational treatment should be adopted as soon as possible. Treatment. In the treatment of cytisine-poisoning we must begin by administering an emetic, etc., so as to procure the elimination of the portions of the plant which have been introduced. So-called chemical antidotes are not of any special value here. Tannin, a priori, might have been thought of use, but, though it throws down a precipitate with cytisine, it dissolves it again when added in excess (Marme). At a later stage of the case stimulants are indicated to avert threatened collapse. Opiates may also act favorably in relieving the jactitation and colicky pains and hy- percatarrhsis. In severe cases, artificial respiration should be had recourse to, for Marme found that animals which had been CICUTA VIROSA, ETC. 827 poisoned with deadly doses of cytisine could be kept alive by artificial respiration. Changes which Cytisine undergoes in the Organism. All that we know about the changes which cytisine undergoes is due to the researches of Marme. Cytisine passes unchanged into the blood, and is excreted again unchanged through the urine, in which it can be detected both chemically and by physio- logical experiment. The chemical test of cytisine, its -extraction from organic sub- stances, etc., have never yet been asked for in evidence. APPENDIX. Poisoning with Cicuta Virosa, (Enanthe Crocata, JEthusa Cynapium. Poisoning with the different parts of the water-hemlock (Cicuta virosa), is tolerably frequent and very dangerous, espe- cially when the root and seeds are in question. Dr. Meyer1 speaks of four children from three to six years of age, who were violently poisoned by eating the roots, which they mistook for turnips. The youngest child died the very same day with pains in the bowels, vomiting, and convulsions in different groups of muscles. The three others had violent pains in the bowels, gid- diness, loss of consciousness, and general convulsions, but re- covered by the use of emetics, tannin, and cutaneous irritation. Schlesiera also observed a very severe case in a child eight years of age, who was found lying unconscious and insensible, with feeble, stertorous respiration, and dilated pupils, the abdomen distended, and meteorism strongly marked. The child was re- stored to consciousness by bleeding, cutaneous irritation, and stimulants; he recovered the power of voluntary movements, the breathing became calm and regular, only incapability of swallow- 1 Med. Zeitg. f. Preussen. No. 40. 1842. 2 Zur Lehre von der narkotischen Vergiftung. Kasper's Wochenschrift. No. 7. 1848. 828 VON BOECK.—VEGETABLE POISONS. ing remained. In spite of this improvement death from collapse supervened the following night. Many similar cases of poison- ing, but generally of a slighter kind, are recorded. The active principle, cicutine, has never yet been isolated in a state of purity, and no experimental investigations have been made into its mode of action. The treatment likely to be most effectual is the use of emetics and laxatives, liquids containing tannin, coffee, etc., also stimulants, camphor, ether,1 etc. (Enanthe crocata has also frequently led to poisoning. Thus Dr. Nicol2 mentions that a woman who was suffering from a skin disease took a decoction of the roots of this plant; very soon loss of power set in, with vomiting and diarrhoea, then convul- sions came on, and death supervened an hour after the decoction had been swallowed. Smiley Kane3 has related a case of a little girl, four years of age, who mistook this root for parsnips; vomit- ing first set in, and then a peculiar rigidity of the whole body, trismus, twitchings of the face and the muscles of the fingers, very labored respiration. Recovery was induced by the use of chloroform inhalations, enemata of turpentine, and stimulants. Bloc4 collected 124 reported cases of poisoning by (Enanthe cro- cata, five of which ended fatally. The root of this plant contains a yellow juice which has a very powerful irritant action, excites coughing, and produces inflammation of the skin like that caused by the nettle. What we find described under the name of cenan- thine and cenanthine resin is not a pure substance, but contains the poisonous principle of (Enanthe crocata. The treatment of poisoning by (Enanthe crocata must be almost identical with that of poisoning by Cicuta virosa. Symptoms of the same kind are produced by the roots of iEthusa Cynapium, which, according to Ficinus,5 contains an alkaloid, cynapine. Evan Thomas6 observed three cases of poi- 1 See Maly, Vergiftung mit Wasserschierling. Oesterr. med. Wochenschrift. Sept. 1844. 3 Case of Poisoning by OEnanthe Crocata. Assoc. Med. Journ. March. 10. pp. 224 and 233. 1854. 3 Med. Times and Gaz. Sept. 25, 1869. 4 Montpellier med. 1872. Oct., Nov., Dec.; and 1873. Mars, Avril. 5 Husemann, Pflanzenstoffe. p. 280. 6 Cases of Poisoning by iEthusa Cynapium. Med. Times. Aug. 1845. CURARINE. 829 soning in children, one of whom died, but the others recovered. All had very violent pains in the stomach and intestine, very violent vomiting, and difficulty of swallowing. In medical litera- ture, a series of this and similar poisonings are on record ; thus, in 1869, five members of one family became ill from eating a veal-pie which had been flavored with fool's parsley instead of ordinary parsley (Chevallier). All recovered under judicious treatment, although violent gastric and paralytic symptoms had set in. Evidences of gastro-enteritis are generally found in the bodies of persons poisoned by iEthusa Cynapium. We have no experi- mental evidence as to the action of this poison, and treatment must be that which has been recommended for the other poison- ings just mentioned. Poisoning by Curarine. Curare. Poisoning by curare is from a practical point of view of very subordinate importance for us, as far as the probability of its occurrence within the range of our own experience is concerned. But this poison has a very strong theoretical interest from a phy- siological and toxicological stand-point. This, as well as the circumstance that curare is employed as a medicine, and has sometimes, though rarely, induced poisoning, may justify our giving it a place here. Curarine is the active principle of a series of poisons which are indigenous chiefly in South America, and which have been prepared by the different tribes of Indians, sometimes from dif- ferent plants, and sometimes mixed up with a number of various ingredients of doubtful nature. It has received the various names of Wurali, TJrari, Macusi Urari, Ticunas, and others. The different kinds of curare are obtained from different plants, and these are only imperfectly known. Thus Strychnos toxifera, Strychnos cogens, Paullinia cururu, etc., yield this poison. Some 830 VON BOECK.—VEGETABLE POISONS. kinds contain mixtures of snake-poison or toad-poison, or other substances which are innocuous, so that the various kinds differ in their poisonous properties. W. Preyer was the first to procure curarine in a crystalline form from curare, and he asserts that this alkaloid acts twenty times more powerfully than curare ; according to others, the difference is not so marked; thus, Bei- gel' states that it is only six times stronger than curare; these conflicting opinions are easily explained by the difference in the original preparation of curare by the Indians. Etiology. . The Indians on the Orinoco, on the Amazon, etc., use curare for poisoning the points of their arrows, with which they hunt animals as well as attack their enemies. Many a European may have been killed in this way. Thus Ferreira de Lemos2 mentions an attack made by the Indians upon the members of a bound- ary commission. One man received three wounds and died in three hours ; others who at once washed their wounds with salt water, were not ill at all, while the secretary of the company, wounded by three arrows, at first showed slight symptoms of curare-poisoning, but remained ill for months simply in con- sequence of the wound as such. W. Preyer3 induced slight curare-poisoning in himself, from some of the powder making its way into his body, while he was pulverizing it for his scientific investigations. He also reports a slight case of poisoning which occurred to a man twenty-three years of age, who by chance had admitted a few drops of solution of curare into a cut. Lastly, cases might be mentioned, which have arisen out of the inten- tional medicinal clinical use of curare, but which, so far as my knowledge goes, have never ended fatally. 1 Berlin, klin. Wochenschrift. 7. 9. 33. 1868 ; and Journ. of Anat. and Physiol. II. 2. 329. '2 Gaz. hebdom. 23. 1867. 3 Sitzung der med. Section der niederrhein. Gesellschaft, in Berliner klin. Wochen- schrift. 40. 1865. CURARINE. 831 Symptoms and Course. We possess very incomplete reports of the symptoms which have been observed in cases of human poisoning by curare, and we must, therefore, supplement them with the symptoms which appear in experiments on animals. Preyer, after having swallowed curare powder, felt violent determination of blood to the head, exceptionally violent head- ache,^ which, however, was of short duration, and a peculiar weariness and disinclination to move, which lasted for several hours. There was also increase of salivary and mucous secretion. In the case of the young man mentioned by Preyer, the symp- toms of poisoning did not set in till five hours after the contact of curarine with the wound; they consisted chiefly in very abundant salivary, sudatory, and lachrymal secretions, increased secretion of nasal mucus, and an increase in the quantity of urine ; later on followed an unwonted sense of freshness and relief. Voisin and Liouville x induced similar slight effects in a series of patients. They observed that curare acts much more energetically in subcutaneous injection than in endermatic appli- cation, but that subcutaneous injection produces very great irritation at the spot where it is applied, creating swelling and violent pain, which may last several days; they frequently observed phlegmonous inflammations produced. The pulse generally becomes rather more frequent and stronger, often dicrotic, and this dicrotism may last several days. The temperature rises from two to three and a half de- grees Fahrenheit. The number of respirations increases four to eight per minute. The quantity of urine is augmented, and it contains sugar ; sometimes an erythematous rash appears on the skin. When Voisin and Liouville administered larger doses, they observed more violent symptoms. These usually set in after from twenty minutes to half an hour or an hour ; the first symptom was a severe rigor, which, according to the constitution of the patient, may last a longer or shorter time, and which is 1 Annal. de Hygiene. Juill. 155. 1866.—Gaz. hebdomad. No. 32-37.—Gaz. des Hop. No. 109, 111, 114. 1866. 832 VON BOECK.r—VEGETABLE POISONS. generally very decided, and accompanied with goose-skin, chat- tering of the teeth, and trembling of the whole body. Then fol- low disturbances in the circulation, cardiac action becomes more rapid, the pulse more frequent and weak; it may rise for four or five hours to 140. Great anxiety, sighing respiration, increased temperature, and disturbances of vision are also observed. The last consists chiefly of double vision and mydriasis ; the latter is by no means constant, but often alternates with myosis. At the same time the lower extremities lose their mobility; the equi- librium can no longer be preserved; the co-ordination of move- ments is disturbed; the patients can neither stand nor move their legs. This paralysis lasts for a quarter of an hour, some- times even for an hour. Consciousness and sensation remain intact; great thirst, violent headache, and, in some cases, con- siderable sudatory secretion are present. Recovery sets in even after such severe symptoms as these. A certain weariness re- mains, especially in the lower extremities ; the increase of tem- perature may also last a few days. The most severe forms of poisoning have not been observed sufficiently in detail in human subjects, but such poisonings have been very frequently produced in animals for physiological pur- poses. When curare has been conveyed into any part of the body of a warm-blooded animal, its head, after some time, falls down, and soon afterwards the whole animal sinks prostrate, without convulsions ; curarized animals are no longer capable of raising themselves completely, and after a while all voluntary movement ceases, nor can any reflex movements be aroused even on the application of strong irritants. Respiration becomes steadily slower and weaker, and very soon ceases altogether. The heart still continues to beat strongly, but naturally only for a very short time. In the case of cold-blooded animals—frogs, for instance—the same paralysis sets in, only with them the heart continues to beat for days, while the paralytic condition remains unchanged. In human subjects also this general paral- ysis occurs, and respiration, in consequence, is arrested, and death rapidly ensues from carbonic acid poisoning. It is impossible to state accurately what amount of curare is sufficient to produce the different degrees of poisoning, as the various sorts of curare CURARINE, 833 which are offered for sale are not equally rich in the active prin- ciple curarine. Voisin and Liouville,1 by doses of 50 milligrammes (three-quarters of a grain), produced only very slight symptoms, but by 150 milligrammes (two and a half grains), violent ones ; but subcutaneous injection of one and a half grains (0.1), four times repeated, failed to produce general severe effects. Rab- bits are killed rapidly by less than half a grain (0.025); frogs are paralyzed by minimum doses, but afterwards recover. Analysis of Symptoms—Mode of Action of Cur are-Poisoning. The most remarkable effect of curare is paralysis of the volun- tary movements, and this action has been diligently studied by distinguished investigators, so that a universal concurrence of evidence has been obtained on this important question. Claude Bernard,2 Koelliker,3 Pelikan,* A. v. Bezold and Heidenhain,5 and others, have made valuable observations on this subject. The cardinal experiment which gives us direct insight into the action of curare is the following : a frog, when the vessels of one leg have been ligatured, becomes paralyzed over the whole body with the exception of this leg ; this leg retains the power of vol- untary movement, and can be moved reflexly by stimulation of any part of the animal's skin. Hence it is clear that the paraly- sis is not central but peripheral, and that sensation remains in- tact. The muscles which have been deprived of movement by curare react to direct stimulation as in the natural condition ; they are, therefore, intact; but the muscle does not react to irri- tation of the motor nerves. The cause of paralysis must, there- ' Loc. cit. and Compt. rend. LXIV. 3. p. 131. 1867. 2 CI. Bernard and Pelouze, Compt. rend. XXXI. 533. 1850; CI. Bernard. Compt. rend. XLIII. 824. 1856 ; CI. Bernard, Lecons sur les effets des substances toxiques. 1857. " Note sur Paction du curare sur le systeme nerveux. Compt. rend. XLIII. 791. Oct. 1856 ; Physiolog. Untersuchungen, etc. Virch. Arch. X. 3 ff.; Zeitschr. f. wissen- schaftl. Zoologie. IX. 434. 4 Virchow's Archiv. XI. 5. 1857; L'Union med. 35. 1857. 6 A. v. Bezold u. Heidenhain, Med. Centralzeitung. 49, 58, 59, 64. 1858; A. v. Bezold, Mueller's Archiv. 2, 3. 1860. VOL. XVII.—53 834 VON BOECK.—VEGETABLE POISONS. fore, be sought in the motor nerves ; but the nerve-trunk is not altered by curare. For we can moisten a nerve-trunk with solu- tion of curare, and yet by stimulating it produce muscular twitching;. But this twitching ceases at once when the muscle is sprinkled with the poison ; therefore it must be the extremi- ties of the motor nerves only which are paralyzed by curare. Thus we find that curare interposes an impediment between the motor nerves and the muscle by paralyzing the intramuscular extremities of these nerves. This action affects all voluntary muscles equally ; therefore it influences the respiratory muscles, and their paralysis must lead to asphyxia. Thus death from curare is shown to be essentially death by asphyxia. The action of curare on the heart, as we have already men- tioned, is not specially prominent, and consists only in accelera- ting the heart-stroke. This increase of cardiac contractions depends upon paralysis of the extremities of the vagus in the heart, which, indeed, according to v. Bezold, do not yield so rapidly to the action of curare as the extremities of the motor nerves do, but yet with large doses of curare they lose their excitability, so much that irritation of the trunk of the vagus is no longer capable of arresting cardiac contractions. When large doses are in operation, the vessels become dilated through paral- ysis of the vaso-motor extremities of the nerves, so that, not- withstanding the increased frequency of cardiac contractions, the blood-pressure is lowered. Irritation of the sympathetic in curarized animals causes no dilatation of the pupils (Koelliker and Zelenski1); but Bidder' disputes this statement and asserts that the sphincter iridis is paralyzed, and that consequently the dilatation (sympathicus) predominates, which accounts for the mydriasis usually observed. No attempt has hitherto been made to reconcile these conflicting views. The intestinal move- ments seem to be more lively and energetic in curarized animals than in the natural condition ; the irritation of the splanchnicus which inhibits the intestinal movements has no effect in animals completely under the influence of curare. This increased peris- 1 Arch. f. patholog. Anatom. XXIV. 362. * Arch. f. Anatom. und Physiolog. 1865. 337. CURARINE. 835 taltic action in the intestine which, according to Dr. Nasse,1 does not occur if the poison cannot flow through the arteries in the wall of the intestine (from ligature or compression) is indirectly dependent on the paralysis of the splanchnicus, since by this paralysis dilatation of the vessels with increased blood-contents and decreased elimination is brought about, and this vaso-motor influence over intestinal movements is, according to S. Meyer's researches, of great importance. As regards the increase of salivary secretion, which accom- panies most cases of curare-poisoning, we have not lighted upon any clear explanation of it; Claude Bernard,3 indeed, succeeded in producing a flow of saliva in animals by the local application of curare to the submaxillary glands themselves, the secretion from the glands becoming continuous. It is probable that in this case also the vessels are paralyzed. The increase of tempera- ture which is observed in the human subject after the applica- tion of curare appears inconsistent with the fact, observed by most authorities, that in animals the temperature is lowered. The increase of temperature in human beings can only be ex- plained by supposing that the small doses of curare which have been introduced cause a contraction of the\essels, thus tending to diminish the loss of heat. When once the vessels become paralyzed the temperature must naturally diminish, as with ani- mals. But this stage is never reached in human beings, because asphyxia sets in so rapidly. The influence of curare on the sensory nerves is extremely slight, and, if we ligature the artery of a leg and so exclude it from contact with the poison, we can, in animals otherwise paralyzed, produce movement in this unpoi- soned leg by irritation of the sensory nerves. Therefore the excitability and conductibility of the sensory nerves, as well as the reflex excitability of the spinal cord, are retained in ordinary cases of poisoning. If, however, very large quantities of curare are employed, and life is maintained b}^ artificial respiration, the spinal marrow then becomes affected, its excitability being at first increased and subsequently paralyzed. Testimony to this 1 Beitrage zur Physiologie der Darmbewegungen. Leipzig. 1866. 61. 2 Journ. de l'anat. et de la physiolog. 1864. 507. 836 VON BOECK.—VEGETABLE POISONS. effect is found in the writings of A. v. Bezold,1 Wundt and Schelske,2 and in those of Magron and Bouisson;3 the motor cardiac centres are also similarly affected by large doses of curare (v. Bezold) ; they are first excited and later on paralyzed. The question whether the conductibility and excitability of the nerve-trunks are affected by large doses of curare is answered in the affirmative by v. Bezold, who observed that when means are taken to bring the motor nerves under the influence of curare, while their muscles are protected from its influence, they convey the stimulation which they have received more slowly to the muscle than when in their normal condition. Thus we find that curare is a poison which primarily paralyzes the extremities of the motor nerves of the voluntary muscles, and later on those of the involuntary muscles and of the vessels, and which tends to cause death by producing paralysis of the respiration; at a later stage and secondarily, the nerve-trunk, the spinal cord, and the motor apparatus of the heart, after initial increase of excitability, also become paralyzed. Its secondary action can only be observed in experiments on animals and by keeping up artificial respiration, because in human subjects death super- venes before these symptoms can be developed. It is not yet ascertained how the presence of sugar in the urine is brought about by curare; and interesting as this question is in itself, its significance in practical toxicology is so subordinate that we are quite justified in dismissing it without further consideration. It is most probable that it is a result of disturbances in the circula- tion. Results of Autopsies. No reports of autopsies on human beings have come within my knowledge; in animals we find the usual signs of death by asphyxia. The blood also, when submitted to spectrum analy- sis, only shows signs of accumulation of carbonic acid (Preyer4). 1 Mueller's Arch. 2. 3. 1860. 2 Verhandlungen des natur-histor. med. Vereins zu Heidelberg. II. 1. I860. 8 Compt. rend. XLVIII. Nov. 4. 1859 ; and Journ. de la Physiol. II. 7. 8. 1859. * Berlin klin. Wochenschrift. 43. 1867. CURARINE. 837 The statement of J. Hoppe,1 that curare produces hyperaemia in various organs, but never in the spinal marrow, is not incon- sistent with the condition usually found after death by asphyxia. Diagnosis and Differential Diagnosis. The recognition of curare-poisoning as such depends on the existence of paralysis of the voluntary muscles with diminished frequency of respiration, while the cardiac action and the senso- rium remain unaffected. The diagnosis will, however, be ren- dered more certain if, in examination, it is found that the patient has been wounded by a poisoned arrow, or if the history of the case can be obtained. It is very easy to confound curare-poison- ing with poisoning by coniine. In Europe, when the question is in doubt, the probability is in favor of coniine-poisoning, espe- cially when there is no external wound. Prognosis. The prognosis of curare-poisoning will be favorable if the sys- tem is under the influence of only small quantities of the poison, and especially, therefore, when the poison has been introduced internally by the mouth. The early summons of medical aid will often have a considerable influence on the issue of the case. The prognosis is unfavorable if large quantities of the poison have been rapidly absorbed into the blood. The slower the absorption from a wound or from the stomach, the more favorable is the course. Treatment. Although curare acts so powerfully on the organism, yet treatment is by no means ineffectual in counteracting its influ- ence. Small doses taken internally are of no consequence, as they produce no symptoms ; large and poisonous doses should, if possible, be eliminated by emetics. The remedies recom- 1 Wiener Zeitschrift. Oct. Nov. 1857. 838 VON BOECK.—VEGETABLE POISONS. mended as antidotes, tannin and iodine, certainly do throw down precipitates with solutions of curare, but they are themselves not innocuous. If there is a surface wound through which curare has been introduced, the limb affected should at once be liga- tured above the wound, e. g., with a caoutchouc band, or with an ordinary strong bandage, and the wound should then be washed. If, after some time, no symptoms of poisoning appear, the bandage may be unfastened, and the blood allowed to circu- late again in the affected limb. But the ligature must be re- newed again quickly, so that as little of the poison as possible may be conveyed into the general circulation, and the residue retained in the wounded limb. If symptoms of poisoning appear after the bandage has been loosened, we must reapply the ban- dage and wait till they subside, after which we may readmit the isolated blood into the general circulation, and follow this plan till all symptoms have disappeared. We may thus succeed in preventing paralysis and preserving life in animals, after large quantities of curare have been subcutaneously injected into the lower part of a limb. If threatening symptoms set in, as slow respiration, dyspncea, anxiety, etc., attention must be directed to the respiratory process, and it must be kept up by stimu- lants, but especially by artificial respiration. Thus animals who had been poisoned with large doses of curare have been saved by continuous artificial respiration. According to Bert's1 re- searches, animals may be saved even when twice the quantity necessary to destroy life has been subcutaneously injected. But if a still larger dose has been introduced, even artificial respira- tion will be of no avail, because such doses cause paralysis of the central organs, the spinal marrow, and the motor cardiac ganglia. In practice we shall find that stimulants, etc., may be advisable, in addition to artificial respiration. Changes which Curare undergoes in the Animal Organism. The active constituent of curare is readily soluble in water, and therefore readily absorbed into the blood; this absorption 1 Empoisonneraent avec le curare. Gaz. med. de Paris. 11. p. 148. 1869. CURARINE. 839 takes place very rapidly from the subcutaneous tissue ; absorp- tion also takes place from the mucous membrane of the stomach and intestine, from the conjunctiva, etc., but much more slowly than from the subcutaneous tissue. The curare which has been absorbed into the blood is very soon eliminated from the organ- ism again, principally through the urine, without having been decomposed in its passage through the body, or having suffered any alteration. Thus the urine of a curarized frog will poison another, and with its urine we can poison a third, and so on. But this cannot be done with any other fluid of the body, the bile, for example.1 It is upon the rapid excretion of curare that we depend for the favorable result of ligaturing the part of the body where the poison has been introduced, and of artificial respiration, which maintains life till the poison has left the body. It is also by the rapid excretion of the poison that we account for the remarkable fact that doses which, injected subcutane- ously, produce very serious symptoms, when taken into the stomach have no effect. A wound poisoned by curare may be sucked without any danger. These facts led to the belief that the poison was inoperative when taken into the stomach, and either was not absorbed or suffered decomposition there. All these hypotheses are false ; curare is slowly absorbed, but is so rapidly excreted again that usually the blood is not sufficiently charged with curare to induce symptoms of paralysis. It has been shown by several investigators, e. g., CI. Bernard, L. Her- mann, and others, that if the renal arteries of an animal are liga- tured, and if then curare is given by the stomach, symptoms of poisoning set in, just as in subcutaneous injection, only more slowly. In this case the excretion of the poison by the kidneys is prevented, and curare is retained in the blood in sufficient quantity to produce the characteristic symptoms. Koch8 dis- covered that the liver of animals poisoned with curare contains a relatively large amount of curarine, and concluded therefrom that the liver absorbs the poison conveyed to it through the 1 Bidder, Reichert's Archiv. 1869. p. 598. 2 Versuche iiber die chemische Nachweisbarkeit des Curarins in thierischen Flussig- keiten und Geweben. Dorpat. 1871. Dissert. 840 VON BOECK.—VEGETABLE POISONS. mesenteric vein and retains it for some time, so that only small quantities at a time return into the general circulation ; in this way he explains the remarkably little effect produced by curare when taken by the stomach. Though the greater proportion of the poison introduced is excreted in the urine, a considerable portion also passes off in the faeces, as appears from Koch's researches. So long as curare circulates in the blood, it appears to be distributed pretty equally everywhere, with the exception of the liver, as mentioned above ; thus Koch found it in almost all the organs and also in the blood itself. Chemical and Physiological Tests. We must search for evidence of the poison, when it has been internally administered, especially in the matters vomited, the urine, and the faeces. If the poison has been endermatically or subcutaneously applied, we must examine the urine in the first place, and then the faeces. In fatal cases, the liver must also be carefully examined. For separating the poison from organic substances, the Koch- Dragendorff method is the most desirable to follow. Add alcohol to the acidulated watery extract to throw down the dissolved albumen, mucous and coloring matters. Shake the filtrate re- peatedly with benzol, or, better still, with amylic alcohol. Evapo- rate the latter to the consistence of syrup, and add alcohol at 95f0. Now filter, add to the filtrate baryta water in excess, and throw down the excess of baryta with carbonic acid. Now evapo- rate the filtrate in a water-bath to dryness, and from the residuum dissolve out the curarine with water. In this way a brownish- red or yellow solution is obtained, to which the physiological test of the poison may be applied. In order to obtain curarine sufficiently pure for the chemical reactions, Koch recommends that we should mix the watery solution with powdered glass and dry it, and then leave it for a long time in contact with chloro- form. The chloroform then leaves the curarine behind in a suffi- ciently pure condition to be recognized chemically as such. The following are the chief reactions of curarine: concen- OPIUM AND MORPHINE. 841 trated sulphuric acid gives to solutions which contain even one- sixteenth of a milligramme (one-thousandth of a grain) of cura- rine a red color, which later on becomes darker, and after about four hours appears rose-colored and is recognizable even after twenty-four hours. Concentrated sulphuric acid and potassium bichromate bring out, as in strychnine, a beautiful blue color, which passes into violet, and later on into cherry-red. This transition is slower in curarine than in strychnine. If a solution of curarine or of curare be heated with dilute sulphuric acid (1 : 50) in a water-bath, the solution becomes reddish, then pur- ple, and later on, with longer heating, black. The physiological test for curarine is more valuable and easier of application. Inject some of the substance to be investigated subcutaneously into a frog or a rabbit, and observe the s}Tmp- toms of paralysis of the muscular apparatus which after some time set in, and to which the rabbit succumbs, whereas the frog generally recovers. Poisoning with Opium and MorpMne. Opium and morphine are used so frequently as poisons that they possess on that account the greatest interest for the phy- sician. The two substances resemble one another so entirely in their effects, that in a manual of practical toxicology, which is to serve as a guide for the practical physician, it will be as well to treat of them together, and by so doing we shall avoid repetition. Morphine (e„H19NO,) is a crystallizable alkaloid, the salts of which are readily soluble in water; pure morphine is sparingly soluble in water, and insoluble in ether. It is the chief constitu- ent of opium, in which it is contained in various proportions from 2.8 per cent, to 20 per cent., according to the kind of opium, the country from which it is obtained, the time of gathering, etc. East India opium contains the smallest quantity of morphine, 2 percent.; the greatest amount is found in that cultivated m Europe, 20 per cent., e.g., that from Provins, Erfurt, etc. The ordinary opium sold by chemists, i. e., Egyptian or Smyrna 842 VON BOECK.—VEGETABLE POISONS. opium, contains between 10 and 13 per cent, of morphine. The German [and U. S.] Pharmacopoeias require that the opium used in medicine shall contain a minimum quantity of 10 per cent. of morphine. As so large an amount of morphine is contained in opium, the poisonous effects of opium are the same as those of morphine. Still opium-poisoning differs in some subordinate points from morphine-poisoning, because opium contains, in ad- dition to morphine, a number of other substances, partly alka- loids, partly also resinous, gummy, and acidulous bodies, be- sides fat, sugar, extractive substances, and salts, which modify the effect of it, and in different degrees, according to the propor- tion in it of these different substances. Narcotine is the ingredient of next importance, as regards quantity, in opium (which, as is well known, is obtained by in- spissating the milky sap of the seed-capsules of Papaver som- niferum), and this is present in opium in the proportion of from 5 to 10 per cent.; it is worthy of notice that those kinds of opium which contain most morphine contain least narcotine, absolutely as well as relatively, and vice versa, so that many have imagined that narcotine is converted into morphine. Nar- cotine (022H23N03) is a crystallizable alkaloid which is almost insoluble in cold water, sparingly soluble in warm water, readily soluble in benzol, amylic alcohol, hot alcohol, and ether, and most readily of all in chloroform. In our present state of knowledge as to the action of narcotine, it must be characterized as having, on the whole, the same kind of action as morphine or opium, but in a less degree. Narceine (023H29N09), an alkaloid which may be extracted from opium in the proportion of one-tenth of one per cent., has a similar effect to narcotine, but more powerful. Narceine in a pure condition is sparingly soluble, whereas its salts are readily soluble. This substance also is quite subordinate in its action to morphine. The same holds good with regard to codeine (OiaH21 NO,), which exists in opium in the proportion of from one-quarter to three-quarters of one per cent. This is not very readily solu- ble in water, but is readily soluble in alcohol, ether, and chloro- form. This substance bears a close resemblance to morphine in its mode of action. OPIUM AND MORPHINE. 843 Thebaine (Ol9H21N03) is found in the proportion of about one per cent, in opium; it crystallizes like the alkaloids mentioned above, is readily soluble in alcohol and ether, sparingly so in water; thebaine acts as an irritant upon the central nervous sys- tem, so that it produces tetanus as strychnine does. This sub- stance, with regard to its physiological action, differs widely from that of opium and morphine, but it is contained in opium in too small a proportion to modify in any special manner the symptoms of opium-poisoning. The action of papaverine (O20H21NO4) is to some extent anta- gonistic to that of thebaine. This alkaloid is insoluble in water, but very readily soluble in hot alcohol; it is a powerful agent in inducing sleep, and paralyzes the motor centres (W. Baxt). Of the substances contained in opium, there still remain to be mentioned pseudomorphine, metamorphine, opianine, porphy- roxine, cryptopine, rhceadine, papaverosine, meconine, meconic acid, caoutchouc, etc., which may be obtained from it in small quantities, and none of which exercise any important share in the physiological action of opium. It has been already said that all the alkaloids of opium do not act in the same way ; but some, and those the majority, have a decided influence in diminishing the excitability of cer- tain special portions of the nervous system, whereas others in- crease the excitability of the nervous system. Tables have been drawn up, classifying the alkaloids of opium according to their action. Thus Claude Bernard,1 who has devoted himself success- fully to the investigation of the action of the opium alkaloids, has drawn up the following table, at the head of which are the alkaloids which have the most powerful paralyzing action, and at the other end those which act most strongly in producing convul- sions : Narceine, Morphine, Codeine, Narcotine, Papaverine, The- baine. A second series has been drawn up by Waldemar Baxt,2 who regards papaverine as the most paralyzing poison, and there- fore places it above narceine. 1 Compt. rend. LIX. 1864. p. 406. et seq. 2 Zur physiologischen Wirkung der Opiumalkaloide. Arch. f. Anat. und Physiol, p. 112 ff. 1869. 844 VON BOECK.—VEGETABLE POISONS. As the proportions of the paralyzing substances in opium far exceed those of the exciting substances, the characteristic of opium-poisoning is its paralyzing effect; and indeed it is these paralyzing qualities which demand the attention of practical toxicologists, as we learn from a vast number of cases that opium and morphine are almost the only poisons used in ordinary life, so that it appears necessary, for a variety of reasons, to consider them. Etiology. Poisoning by opium and morphine occur whenever substances containing opium and morphine in excessive doses are introduced into the organism, and become incorporated with the blood. Such substances are, in the first place, opium itself, and the medicinal and pharmaceutical preparations prepared from it: extract, tinc- ture, and wine of opium ; syrup of poppies ; morphine and its salts, especially the hydrochlorate, sulphate, and acetate ; also the leaves, seeds, and seed-capsules of the poppj^,1 which have been administered in infusions or decoctions, especially by lazy nurse-maids to the infants under their charge, to put them to sleep. Children have also been poisoned by eating the blossoms and fruit of the Papaver Rhoeas.2 We have an immense number of cases reported in modern times of poisoning, in England and America, from the use of nostrums containing opium and mor- phine : Black drops, Godfrey's elixir, Dalby's carminative, Batt- ley's sedative solution, etc. All contain opium, and may cause poisoning as effectually as the other preparations of opium used in medicine. The poisoning produced by these drugs is mostly medicinal, caused by carelessness in prescribing8 or dispensing, or they have arisen out of other accidents, e. g., mistaking one drug for another in chemists' shops ; thus a number of cases of poisoning by morphine have been published in late years (at 1 A. Chevallier, Journ. de chimie medic. Aout. p. 365. 1869; Sulzmann, Badische artzl. Mitthlg. 1868. 2 Palm, Wurtemberg. med. Corresp.-Blatt. 1855. No. 33. 3 Thus the Journ. de chim. med. p. 139. 1868, relates a case of fatal poisoning, caused by the doctor's ordering, in his hurry, 12 grains of morphine instead of £ a grain. OPIUM AND MORPHINE. 845 Vienna, Berne, Carlsruhe, etc.), which have arisen partly from dispensing chemists confounding drugs, and giving hydrochlorate of morphine instead of hydrochlorate of quinine, partly through confounding the substances in the manufactory which furnished them. Opium and morphine have been largely used for com- mitting suicide, especially by medical men, chemists, etc. Mor- phine has also been used with the intent to murder, as we learn from the case of Dr. Castaing,1 although it would appear, from its bitter taste, ill-adapted for this purpose. There are also in- stances of persons who have been stupefied by opium and mor- phine in order to rob them more easily; and there are many cases of poisoning described in which tincture of opium instead of tincture of rhubarb has been taken in tablespoonful doses. The manner in which the poison is conveyed into the system is comparatively unimportant; cases of poisoning have been ob- served not only from the internal administration, but also from morphine and opium being used in the form of enemata or sup- positories, or even by endermic or subcutaneous application ; even simple fomentations2 with opium on the healthy, uninjured skin have produced symptoms of poisoning. The symptoms of poisoning naturally appear early, if the poison has been rapidly absorbed into the blood. This absorp- tion, especially in cases of internal administration, is, however, dependent on a series of factors : the fulness or emptiness of the stomach is an important one; the emptier the stomach, the more rapid the absorption ; the form in which the substance has been administered is also an important consideration. Opium powder acts more slowly than tincture of opium, pure morphine more slowly than hydrochlorate or acetate of morphine, which is the most rapidly dissolved; the effect of subcutaneous injection is veiy rapid; when the poison is injected into the veins the symp- toms set in almost instantaneously. 1 Castaing poisoned his friends, the brothers Ballet, in 1822 and 1823 ; the death of the latter was caused by morphine and tartarized antimony; he was condemned at Paris. Also at Lambeth workhouse, in London, according to Pharmac. Journal, p. 597, 1868, a man seems to have been intentionally poisoned with morphine by an attendant. 2 Taylor relates in his work "On Poisons," translated by Dr. Seydeler, III. Vol. p. 16, a case in which a soldier died in consequence of fomentations which he had to apply to an erysipelatous leg, and which had been moistened with an ounce of laudanum. 846 VON BOECK.—VEGETABLE POISONS. It is impossible to state accurately what quantities of opium and morphine are sufficient to cause death. A strongly marked difference exists between the cases of adults and children ; the latter in the first years of life are very susceptible to the action of opium. As regards adults, John Dougalll relates a case of suicide in a woman, who took one drachm (= about 4.0) of tincture of opium and died notwithstanding medical treatment. According to Taylor,2 the smallest dose of opium in substance known to have caused the death of an adult is two and a half grains of extract of opium, equal to four grains of raw opium. Of morphine, naturally, much smaller doses are fatal; a dose of even one and a half grains (0.1) of a salt of morphine may prove very dangerous. But daily experience and many clinical cases that have been published prove that much smaller doses of opium and morphine may produce violent symptoms of poisoning without actually causing death. The individual constitution plays a very important part in narcotic poisoning ; for example, there are cases of persons who have recovered even after enormous doses of opium and mor- phine ; thus Taylor mentions in his manual (loc. cit.) cases which ended in recovery, although four and five ounces of tincture of opium had been taken. In a later case given by Bare,3 a man, who had taken ten drachms of tincture of opium (= 40.0), re- covered without vomiting. Cases are also reported of recover}^ after large doses of mor- phine. Bonjean 4 witnessed a recovery after twenty-five grains (= 1.5) of acetate of morphine. Bergsten5 saw an apothecary recover after six grains (0.4) of morphine acetate ; Lyons6 reports the recovery of a girl, five years of age, who had been poisoned with four and a half grains (0.3) of morphine. 1 Glasgow Med. Journ. May. p. 339. 1872. 2 " On Poisons," translated into German by Seydeler. 1868. Vol. III. p. 25. 3 Philadelph. Med. and Surg. Reporter. Jan. 6. 1869. 4 See Husemann, Handbuch der Toxikologie. I. Vol. p. 597. 1863. 5 Lakare foren Forhandlungen. VII. p. 647. 1872. 5 New Orl. Joum. of Med. p. 293. 1869. OPIUM AND MORPHINE. S47 Certain diseased states seem to blunt the effect of opium, so that colossal doses are often borne. To these belong all forms of mental alienation. In a case related by Model,1 a female maniac took eighteen grains (— 1.1) of acetate of morphine, and was found pulseless and scarcely breathing, yet she recovered com- pletely after a few hours. Kellok5 gave a woman suffering from puerperal mania, thirty grains (= 1.9) of morphine muriate in twenty-four hours, without any consequent poisonous effect. On the other hand, I myself witnessed a case in which a woman suffering from maniacal attacks, had about three grains (= 0.18) of morphine subcutaneously injected in the course of two hours, without being quieted : sleep and collapse set in after two hours, in which the patient sank. Further, it is well known that in tetanus, delirium tremens, hydrophobia, and poisoning by strychnine and atropine, very large doses of opiates are borne; the same is the case with cancer, peritoneal diseases, neuralgia, etc. A mighty influence is also exercised by custom. There are persons, especially those suffering from chronic diseases, who from small doses of opium go on to larger and larger doses, in order to obtain sleep or a few hours' freedom from pain, and who bear doses which would speedily destroy life in healthy people. Every hospital and almost every physician has such cases to • report. It is needless to say that such persons require enormous doses of opiates to produce poisonous effects, as the system has become accustomed to the poison. On the other hand, there are persons who are highly sensitive to opiates, and are made severely ill by even small doses ; this we call idiosyncrasy. Thus Christison 3 speaks of a man who was thrown into a state of sopor by from one-third to one-half of a grain (= 0.02 to 0.03), and Stein'thal4 witnessed a serious case of poisoning from one grain (= 0.06) of opium, administered in an enema. 1 Bayr. Intelligenzblatt. No. 46. p. 572. 1871. 2 See Husemann, loc. cit. 3 See Husemann, Toxikologie I. Vol. p. 597. 4 See Husemann, loc. cit. 848 VON BOECK.—VEGETABLE POISONS. In Donyan's' case -fa of a grain (= 0.002) of morphine endermi- cally applied produced violent narcotism, hemiopia, etc. In the Lancet of March 21,1863, a case is described in which a woman, four or five hours after taking two drops of laudanum, was seized with rigors, loss of sight and hearing, and became covered with a rash resembling scarlet fever. It is remarkable, that poisoning often occurs from doses which have often at other times been given without any particu- lar result. Perhaps this may depend on accidentally rapid ab- sorption. It cannot certainly be a case of cumulative action. On the other hand, we find on record a long series of recov- eries after large, and even very large, doses of opium, quite apart from cases in which perhaps the greater part of the poison has been eliminated before it was absorbed, therefore, before its action began. Children assume a special position with regard to opiates. We may say in general, that the younger children are, the more sensitively they react to opium and morphine. They retain this sensitiveness during the first year of their lives, and some- times even up to five years of age. A number of cases have been published, in which minimum doses of this poison have proved fatal to children. Taylor2 has collected a number of such cases, in which y\7, TV, \ of a grain of opium, or one, two, three, and four drops of tincture of opium caused death. In a case given by Schmidt,3 ^ of a grain (= 0.003) of opium caused the death of a child. And yet cases are not wanting in which much larger doses have been borne by children, without killing them. Thus in Corbet's4 case, thirty drops (=1.9) of laudanum were adminis- tered to a newly-born child : very alarming symptoms followed, and yet recovery set in after five hours. In a case mentioned by Blank," a little boy three weeks old, to whom three enemata 1 Empoisonnement par une dose extremement faible de morphine. Gaz. des Hopit. 1844. 2 On Poisons, etc. Vol. III. p. 29 ff. of Seydeler's Translation. 3 Gaz. des Hopit. No. 16. 1855. 4 Lancet. II. 9. Aug. 1857. 6 Rev. de therap. med. chirurgie. 17. 1857. OPIUM AND MORPHINE. 849 with thirty-five drops of laudanum each had been administered, recovered the following day, notwithstanding very violent symp- toms. Another child J took a teaspoonful of tincture of opium, and recovered under simple treatment. It will thus be seen that it is scarcely possible to fix the doses of opium or morphine which must be regarded as fatal. As soon as a sufficient quantity has entered the circulation, to disturb the functions concerned, symptoms of poisoning set in. The period of the appearance of the first symptoms varies considerably. Pathology. Symptoms and Course. The group of symptoms produced in human subjects by opium or morphine may serve as the prototype of all simple narcotic poisonings. The ordinary sequence of the symptoms corresponds with a reduction of the excitability of the nervous centres, preceded by a longer or shorter stage of increased excita- bility. As soon as a sufficient quantity of the poison has entered the circulation, a condition of mental excitement of a pleasurable character sets in, physical activity, restlessness of the limbs, roll- ing of the eyeballs, acceleration of cardiac action, sometimes hallucinations of a cheerful and agreeable nature: at the same time there are dryness in the throat, increased thirst, and oc- casionally sexual excitement. Whether the doses have been considerable, or only such as are usually ordered medicinally, this condition never lasts long; it is gradually replaced by head- ache, weariness, a sensation of weight in the limbs, incapacity for exertion, sleepiness, disturbed sleep, diminution of sensibility, and generally great contraction of the pupils. In this semi-som- nolent stage, circulation and respiration remain normal. But soon this state, from which the patient may be roused, or durino* which he may even be kept awake by speaking to him in 1 Plum, Hospit. Tidschr. 1868. VOL. XVII—54 850 VON BOECK.—VEGETABLE POISONS. a loud voice, shaking him, or by communication of pain in some way, passes into complete coma. The patient lies motionless on his couch,cannot be awakened; sharp blows make no impression upon him ; reflex action ceases altogether; the eyes are generally half shut; the pupils are strongly contracted (very rarely dilated), and do not react to light; the muscles are relaxed; if one of the limbs is lifted up it falls back as if paralyzed, the lower jaw falls, the skin is cold to the touch, the appearance of the patient is either pale and livid or dark and cyanotic—in short, he is like a dead man, respiration and pulsation being the only signs of life; but these functions also have suffered considerably under the influence of the poison ; respiration has become slow, la- bored, irregular, and stertorous ; it may even be accompanied by various mucous rales ; the action of the heart has become slower and more irregular, the pulse is more feeble, very compressible, often difficult to feel; still, under favorable circumstances, the patient may awake out of this stage of complete narcosis and recover. But in the most serious cases the symptoms are still more aggravated. The respiration and the pulse become still slower and feebler, the cyanosis increases, the skin becomes colder and covered with cold perspiration, the noisy rales increase, certain muscles and groups of muscles manifest tremulous, clonic twitchings of short duration ; the pupils are frequently dilated in this stage, sometimes, though rarely, actual trismus and teta- nus set in ; salivation is also observed in some instances. And thus death majr slowly supervene with gradual extinc- tion of the pulse and respiration, or paralysis is rapidly devel- oped, and collapse puts an end to suffering. Cerebral hemorrhage sometimes occurs during the progress of the case, and this itself may ultimately prove fatal. One constant symptom through the whole course of the case is suppression of the urine and fgeces, but sometimes, especially at the beginning and the close of the case, we may meet with marked symptoms of strangury. In almost all cases of opium- and morphine-poisoning we meet also with very profuse perspiration. When the case takes a favorable turn, the first sign of im- provement is in the respiration and pulse becoming more regular; OPIUM AND MORPHINE. 851 blood-pressure increases, while the comatose symptoms grad- ually subside and are replaced by a lighter soporific state, out of which the patient can be roused, though it may often last twelve to twenty-four hours. But cases have occurred where the patient had been completely roused, and there was hardly any doubt of eventual recovery, which nevertheless ended fatally from the relapse into stupor, sopor, and coma, and finally paral- ysis. It is very probable that in these cases there is a renewed absorption of poison, perhaps under the influence of increased blood-pressure. Again, cases are on record in which, after the symptoms of acute opium- and morphine-poisoning had com- pletely disappeared, death supervened from affections of the heart or the lungs. In these cases it is highly probable that heart-disease existed previously to the introduction of the poi- son, and that under the influence of the poison the heart became paralyzed, and death followed from asphyxia. In such cases, therefore, opium-poisoning is only a secondary cause of death, and it does not follow that the patient is narcotized at the moment of death. Taylor relates some such instances,1 and one especially (A. Stafford) is important, because the patient was able to undertake a journey on the sixth day after the poison- ing, and did not die till the eleventh day. He had been bled for gall-stone and had lost thirty ounces of blood, and had taken in four hours 200 drops of laudanum and 200 drops of tincture of hyoscyamus. At the autopsy serum was found effused in the pleura, in the pericardium, and in the subarachnoid space ; the heart was found to be enlarged, with very soft, thin walls in a state of fatty degeneration. Here death was certainly not the result of opium-poisoning, but arose from heart-disease, for the heart, especially after so much blood had been withdrawn, could no longer, under the influence of opium, contract with energy, and thus opium was indirectly responsible for the fatal result. More recently a case has been reported by Duchek,2 in which the symptoms of poison intermitted for five days ; in the morn- ing the sopor had generally disappeared, but in the evening it 1 Loc. cit. pp. 10, 11, 12, 13. III. Vol. (Seydeler's translation). 2 Wiener Wochenblatt. XVII. 43. 1861. 852 VON BOECK.—VEGETABLE POISONS. recurred very strongly, attended with alarming disturbances of circulation and respiration. Complete recovery did not set in till the thirteenth day. Certain cutaneous symptoms appear occasionally in opium- or morphine-poisoning, but are not constant. Before the soporific stage sets in the patient often complains of violent itching of the skin, which is quite unendurable, and which is often followed by an exanthem, which consists of wheals, and has a complete resemblance to urticaria; but this form is not strictly main- tained, for it sometimes appears as papulous and roseolous patches. Steinboemer1 mentions the occurrence of a vesicular eruption after one-sixteenth of a grain (= 0.004) of morphine; one-eighth of a grain of opium produced the same eruption. It lasted about eight days, and in the first case was confined to the front of the left arm, which was at the same time swollen. An exanthem resembling scarlatina appeared in the face, arms, hands, neck, legs, etc., of a lady2 five hours after she had taken two drops of laudanum ; she was also seized with rigors and loss of sight and hearing for some time. Vomiting is not a constant, but under certain circumstances a very important symptom. In many cases spontaneous vomit- ing sets in soon after the introduction of the poison, and thus any opium or morphine remaining in the stomach is eliminated, and in many cases this contributes to eventual recovery. Fre- quently, however, a condition of nausea with repeated vomiting comes on towards the close of the case. In children who have been poisoned with opium, convulsions of various muscles are very frequently observed. Strabismus and convulsions of the facial muscles have been especially observed ; and even trismus and tetanus, chiefly in the form of opisthotonus, have been no- ticed. In adult males priapism sometimes appears during the stage of narcosis, but more commonly in that of excitation. It is difficult to say what is the precise length of time from the introduction of the poison to the beginning of the symptoms 1 Schuchardt's Zeitschrift, p. 367. 1866. - Lancet. March 21. 1863. OPIUM AND MORPHINE. 853 of poisoning. Whereas in the cases reported by Nussbaum • and Woodhouse Braine,2 in which poisoning occurred through the accidental injection of morphine into the venous system, most violent symptoms were developed in a few seconds : congestion in the head, violent cardiac palpitation, throbbing of the caro- tids, giddiness, sensations of faintness, anxiety, dyspncea, con- vulsions of the facial muscles, sudden falling down as if dead; in ordinary injection into the subcutaneous cellular tissue, about five minutes elapse before its action begins to make itself felt. When the poison has been conveyed into the stomach, the symp- toms set in later, perhaps after ten to fifteen minutes ; with tinc- ture of opium it requires a longer time, with opium powder longer still. A full or empty state of the stomach has, of course, a decided influence. It is of more importance, in connection with medical evidence in courts of justice, if we could say definitely up to what period the poisoned person is still capable of respon- sible acts; from this point of view there is an interesting case given by Taylor,3 which proves that a man who had been poi- soned with opium had time enough to hang himself; and an- other case, in which a man who had taken half an ounce of laudanum was able to converse animatedly with his neighbor two hours afterwards. An interesting case is given by N orris,4 in which an apothe- cary, who had taken seventy-five (?) grains (=4.7) of morphine muriate, was able to walk for an hour and a half before symp- toms of poisoning set in; he then recovered under a combined treatment, during which he took fifty grains of extract of bella- donna, Opium and morphine introduced by the rectum also acts with considerable rapidity, and produces symptoms as violent as when taken into the stomach.5 As to the time during which the influence of the poison may last, much may be gathered from what we have already said. As a general rule, we may say that poisoning by morphine 1 Bayr. arztl. Intelligenzblatt. 1865. p. 36. 2 Med. Times. Jan. 4. p. 8. 1868. 3 Loc. cit. III. Vol. p. 9. 4 Hays' Americ. Journ. 1862. October. * Alden, Philad. Med. Times. May 15. 1871. 854 VON BOECK.—VEGETABLE POISONS. lasts the longer, the larger the dose, the more complete the ab- sorption, the less the vomiting, and lastly, the less the patient had been accustomed to opiates. Sometimes the stage of excitement lasts a long time ; it is generally shorter comparatively in the case of Northerners than in that of Orientals, with whom these symptoms of excitement persist for a long time. Thus Christison in his book on poisons mentions a case in which excitement lasted eighteen hours after two ounces (= 60.0) of laudanum had been taken, and not till then did somnolence set in. John S. Boyd' describes the case of an insane person, in whom two ounces (= 60.0) of laudanum after twenty minutes produced no effect, and it was not till four- teen hours after that somnolence appeared; death supervened sixteen hours later. The stage of narcosis generally lasts twelve to eighteen to twenty-four hours. According to Christison, death occurs between eighteen and twenty-four hours after morphine- poisoning ; but cases have been observed in which death super- vened much later ; thus AY. Boyd Muschet2 relates the case of a child, three months old, who did not die for fifty-six hours after taking an indefinite dose of opium ; in the interval a short re- mission of the symptoms had taken place. If death is not the result, it may be very long before real recovery sets in ; thus we find a case in the Lancet, in which a woman, thirty-nine years of age, after taking three drachms (= 12.0) of laudanum, did not recover till the fourth day, notwithstanding the use of bella- donna. If morphine-poisoning takes a favorable turn, recovery is generally complete, very seldom incomplete. In incomplete recovery some symptoms remain behind for a longer or shorter time. In the first place nausea is to be included among these, then loss of appetite, impaired digestion, feeling of weariness, headache, giddiness, uncertainty of movements ; all these symp- toms disappear after some time (hours); it is needless to say that if sanguineous apoplexy should occur during the action of the poison, the disturbances depending on this will not disappear. 1 Brit. Med. Journ. Oct. 10. 1868. 2 Medic. Times and Gaz. March 20. 1858. 5 Lancet. Sept. 1868. OPIUM AND MORPHINE. 855 Besides the exanthemata mentioned above, a number of other symptoms deserve notice: as contraction of the pupils,1 which may last some days; slight albuminuria,2 numbness3 or tingling of the fingers, flexion of the thumbs ; in another case a lady poisoned by a very large dose of tincture of opium, by enema, could neither taste nor see for several days after her recovery.4 There frequently remains, especially in opium-poisoning, a tendency to obstinate tenesmus for some time, and this is the most noticeable sequel of opium-poisoning. Chronic Opium- and Morphine-Poisoning. The habitual use of opiates, whether medicinally or from a bad habit, leads to chronic opium-poisoning. By far the greater number of cases of chronic poisoning occur in the East and Asia, especially China, India, Persia, and Turkey. In these countries opium-eating, as well as opium-smoking, is very common ; we learn how often this custom has been the subject of medical treatment from the reports of James Johnston,6 who had occasion to treat about 300 cases of opium-poisoning, seventeen of which were severe and six mortal, in the Chinese Hospital at Shanghai. What the consumption of opium in these countries is appears from the following figures : ° at Samarang, a town with 1,254,000 inhabitants, the average quantity of opium consumed monthly is 7,980 pounds. The town of Japava, with 671,000 inhabitants, consumed, in fifteen days, 5,389 pounds of opium. In the year 1850 over 576,000 pounds of opium were imported into Java ; that is, one-eighty-second of a pound per head ;7 it is impossible to calculate how much was smuggled. But in the West also, espe- cially in England.8 and chiefly in the so-called manufacturing 1 Model, loc. cit. 2 Olivier, Gaz. des Hopit. p. 124. 1871. 3 Woodhouse Braine, loc. cit. 4 Finlay, Lancet. No. 21. 1868. 6 Med. Times. 1872 and 1873. 6 Archiv fiir Pharmazie. p. 559. 1873. ' Van Dissel, Med. Times and Gaz. May 18. 1867. 8 Hawkins, Pharmac. Journ. Feb. p. 396. 1868. 856 VON BOECK.—VEGETABLE POISONS. districts, in Lincolnshire and Norfolk, opium-eating is constantly on the increase. In these districts an apothecary sold, in one year, 200, another, 140 pounds of opium. The causes assigned for this opium-eating in England are the ill-nourished condition of the lower orders, and the frequency of painful illnesses, need- ing the prolonged administration of opium, after the cessation of which the custom of taking opium was continued. Since the subcutaneous injection of morphine has become general, this also begins to spread as a bad habit. Here also the first injections are usually for the relief of painful affections; but after a time the patients become dependent on the injections, and cannot do without them, so that a considerable number of mor- phine injectors have sprung up—chiefly young doctors — who carry on this pernicious practice, as well as patients themselves, who have been intrusted with the injection-syringe by their doctors. Chronic opium-poisoning produces a series of symptoms which are tolerably constant, and are described by a number of medical men and travellers. The most prominent symptoms are general emaciation, a pale, shrivelled complexion, relaxation of the muscles, 1 Jure of the appetite, disturbed digestion; at the commencement obstinate tenesmus, followed later on by dysen- teric diarrhoea. To these are superadded a series of cerebral symptoms: fanciful, discontented temper, giddiness, headache, sleeplessness, all possible eccentric neuralgias, failure of memory, understanding, energy, and will; patients become untrustworthy, and are very regardless of truth, especially when they are ques- tioned about their habit; also paralysis, diseases of the bladder, etc., are apt to set in. I saw, a short time ago, the photograph of a Javanese opium-eater, and I can only confirm Hammer'sl comparison of the class to " exhumed corpses." Chronic meco- nismus generally terminates in an early death, yet there are cases recorded of opium-eaters who have pursued the custom for thirty and forty years, and lived to seventy or eighty years of age. Thus the case of a doctor2 is related, who, for forty-seven 1 See Husemann's Toxikologie. 1862. p. 609. 8 Fleming, Brit. Med. Journ. Feb. 15, 1868. OPIUM AXD MORPHINE. 857 years though with intermissions, took large quantities of tinc- ture of opium-one ounce (= 30.0)-daily, and at the same time attended to the duties of a large and laborious practice as accou- cheur. To what extent opium-eaters pnsh the habit is proved by their own confessions in ancient1 and modern2 times. A woman forty-four years of age took a gallon of tincture of opium monthly, and suffered eventually from sleeplessness and head- ache, but could not wean herself from the habit. I can state from my own experience how far our morphine injectors go ; I know several colleagues who have reached a gramme (15 gr.) of morphine muriate, and even more, per day. Opium-eaters are not, however, secure against acute opinm-poisoning, as, e. g., is proved by a case described by Ludlow,3 in which an opium-eater once took a whole ounce of laudanum instead of his usual half ounce, and very nearly died of it. Even children can be made opium-eaters, as is seen by the reports from the above-named manufacturing districts. Opium is given to them from their birth, and the dose soon reaches 20 to 25 drops per day, but they look very miserable and die within the first two years of their life of atrophy or hydrocephalus (Grainger). Morphine injection also exercises an influence on those addict- ed to it, especially as regards the mind ; but they have usually a good appetite, and their digestion on the whole is not dis- turbed ; they drink but little beer and wine, and hardly smoke at all. I have known cases in which persons have had morphine subcutaneously injected every day for ten or fifteen years, with- out their looking particularly ill. Opium-smokers do not appear to succumb so rapidly to the effect of chronic meconismus as those who eat or drink opium ; at least their appetite does not wholly fail, and the disturbances in defecation are much slighter. Cases are well known of chro- nic illnesses which require large doses of opium for a long time, often for years, yet the patients do not fall victims to morphis- 1 Confessions of an Opium-Eater. Husemann's Toxikologie. 596. 5 W. Whalley, Confessions of a Laudanum-Drinker. Lancet. No. 2. 1866. p. 35. 3 Brit. Med. Journ. July 7. 1866. 858 VON BOECK.—VEGETABLE POISONS. mus or meconismus ; therefore Macpherson may be partly right in regarding moderate indulgence in opium as innocuous. Opium-smokers exhibit the same symptoms as opium-eaters, although it is perhaps a question whether the morphine is not decomposed at that high temperature. Analysis of Symptoms—Mode of Action of Opium and Mor- phine. Opium and morphine are substances which act mainly on the nervous centres and upon the nervous system generally. As these differ in different men, and still more so in different classes of animals, experiments on animals can only throw light on the symptoms of poisoning in human beings in so far as the symp- toms produced in them agree with those observed in the human subject. How carefully we must proceed in our deductions from the animal to the human subject with regard to these very poisons, is shown by the circumstance that some animals—pigeons, for instance—can with difficulty be poisoned by morphine; that other animals, e.g., frogs, after opium regularly manifest tetanic symp- toms, but not so constantly after morphine ; further, that dogs, cats, etc., can often take enormous doses without their producing narcotism or death. Nevertheless it is from experiments on animals that we obtain the best knowledge of the action of these poisons, and of the sequence of the symptoms. The influence of morphine upon the heart is seen when poi- sonous doses are given, and consists, in animals also, in initial acceleration of cardiac contraction, which is succeeded by dimin- ished frequency of pulsation, and ultimately by absolute cessa- tion of cardiac action, the contractions becoming irregular shortly before death. The cause of the initial acceleration of the cardiac action has not yet been sufficiently elucidated by experiments ; but it seems very probable, from the researches of Gscheidlen, that the musculo-motor elements in the heart are first stimulated by morphine, for when he had divided the vagus of a dog or rabbit before poisoning with morphine, the frequency of pulsa- OPIUM AND MORPHINE. 859 tion increased still more after the poisoning ; this experiment seems to support the above conclusion, more especially as the influence of this poison on the sympathetic is comparatively slight. The subsequent retardation of cardiac contractions, how- ever, depends upon an excitement of the vagus at its origin in the brain, for, in the first place, the retardation does not occur when the vagi have been divided before the poisoning; and secondly, the retardation sets in immediately when solution of morphine is injected into the peripheral end of the carotid, there- fore in the direct current towards the brain.' At the same time, the extremities of the vagus in the heart are thrown into a state of increased excitability ; with large doses of morphine, however, the extremities of the vagus become paralyzed; consequently, with very large doses of morphine, the pulse ought eventually to become again more frequent (through paralysis of the vagus); but it is not so, and for this reason, that, as Gscheidlen has shown, morphine exerts eventually a paralyzing action also on other portions of the heart, especially on the excito-motor gangli- onic cells in it. »But the cardiac muscle also experiences a con- siderable loss of excitability, and remains motionless when strong currents are brought to bear directly upon it. Therefore, cardiac contraction must always diminish more and more, till it ceases altogether. Morphine exercises first a constricting, then a dilating influ- ence on the vessels, through the vaso-motor nerves which are primarily excited, and subsequently paralyzed at their centres. Gscheidlen succeeded in directly observing this influence on the vessels in the abdominal cavity of animals ; the peripheral por- tion of the vaso-motor system is affected in the same way even when the influence of the central organ is cut off by division of the cervical marrow. In severe poisoning complete paralysis of the vaso-motor centre- takes place, but not complete paralysis of the peripheral vaso-motor nerves, for these can still be stimulated by direct irritation or from the cervical marrow, so as to produce contraction of the vessels. 1 Gscheidlen, Untersuchungen a. d. physiolog. Laborator. in Wiirzburg. zig. 1869. 860 VON BOECK.—VEGETABLE POISONS. The blood-pressure is in accordance with this condition of the heart and its vessels ; according to Gscheidlen it rises at the beginning of the action of morphine, and even when the pulse becomes slow this increase of blood-pressure still continues, a circumstance doubtless depending on the vaso-motor contraction of the vessels; subsequently the blood-pressure becomes sub- normal, a natural result of the dilatation of the vessels and the diminution of cardiac force. As in human beings, so also in animals, respiration is retarded ; this retardation proceeds from diminished excitability of the respiratory centre in the medulla oblongata, as Gscheidlen's experiment proves, in which, upon injection of the poison towards the brain through the peripheral extremity of the carotid, retardation of respiration at once set in. This diminution of the activity of the respiratory centre may lead to complete apncea, and so to death by asphyxia. Contraction of the pupils is observed in animals as well as in men; this symptom probably depends on excitement of the oculo-motor nerve. According to O. Nassex morphine and opium increase intes- tinal movements, and the intestine is more sensitive under their influence to other excitations. This may account for the effect of opium and morphine in producing tenesmus, and not, as is generally assumed, inactivity of the intestine. In human subjects some dryness in the throat, though not very considerable, is observed; in dogs violent salivation gene- rally occurs, which depends either upon reflex irritation of the gustatory nerves, or upon the influence of morphine on the calibre of the vessels, or perhaps upon an action upon the secre- tory filaments. The peripheral motor nerves, by the direct application of the poison, are at first thrown into a state of excitement, which lasts only a short time (Gscheidlen), and then into the opposite condi- tion of greatly diminished excitability ; daily experience teaches us that the sensory nerves and nerve-extremities in the human subject are similarly affected, for when we administer a subcu- taneous injection of morphine the nerves lying nearest to the 1 Beitrage zur Physiologie der Darmbewegungen. Leipzig. 1866. p. 58. OPIUM AND MORPHINE. 861 point of application suffer greater reduction of excitability than others; it is very difficult to demonstrate this in the case of animals. This influence of the nerves is in itself an obstacle to reflex action, and a considerable impediment to the operation of the will. The influence of morphine upon the cerebrum is very marked, especially on its gray matter, the excitability of which is reduced in a very remarkable manner. Though we find no anatomical changes in the brain to explain this influence, and though most probably the hyperamria of the brain commonly found is not a primary, but a secondary effect, yet a simple anal- ysis of the symptoms affords evidence that the action of opium determines a change in the excitability and the excitement of the individual ganglionic cells, so that there is at first an increase and later on a diminution of this excitement. If these gan- glionic cells come completely under the influence of morphine, no impulse, no expression of the will can be carried into effect; the influence of the brain is to a certain extent eliminated. As to its possible influence on the spinal marrow we have no experimental evidence, but it may be concluded from analogy that the excita- bility of the spinal marrow is affected in the same manner as that of the rest of the nervous system; it is evident, however, that the influence upon the spinal marrow in the human subject is less marked than that upon the brain. The convulsions which occasionally come on during mor- phine-poisoning, and which correspond to opium-tetanus in frogs, might be supposed to proceed from excitement of the spinal marrow at a time when the reflex inhibitory centre, the brain, is already in a condition of diminished excitability. The compar- atively rare appearance of this symptom, however, proves that the changes in the two organs proceed almost pari passu. The vomiting, which is so frequent a symptom, must, in most cases, be due to irritation of the vomitory centres by the poison; at any rate, the circumstance that vomiting sometimes occurs after the poison has run its course and convalescence has set in points to a central origin. The action of the poison upon the urinary bladder is in har- mony with its other effects ; it first causes irritation of the detru- 562 VON BOECK.—VEGETABLE POISONS. sor urinaria vesica with consequent dysuria, later on paralysis of the same muscle, so that in the dead body the urinary blad- der is found distended, while there may be dysuria during life. The most characteristic symptom of chronic opium- and mor- phine-poisoning is general disturbance of nutrition ; this, how- ever, is not the result of increased tissue-degeneration or of accelerated tissue-change, but is due to diminished absorption of food in consequence of the catarrh of the stomach and intestine which exists. This defective nutrition can never give rise to a sensation of hunger, on account of the steady simultaneous re- duction of the impressionability of the sensory nerves. The excreta of persons in this condition, though less than in the nor- mal state, are nevertheless in excess of the ingesta ; hence the result is complete emaciation. Much has been written upon tis- sue-change under the influence of morphine and opium, and it has been generally maintained that change of tissue is retarded ; Boecker1 especially maintained that the solid constituents of the urine were diminished under the use of opium. Experiments which I have made with morphine on dogs with the necessary precautions2 showed that by the use of morphine the decompo- sition of the nitrogenous tissues suffers a very slight decrease— a result which depends on the diminution of blood-pressure and of the flow of fluids through the parenchymatous tissue. A fur- ther investigation carried out by Dr. J. Bauer and myself,3 as to the excretion of carbonic acid under the influence of morphine in dogs and cats, showed that morphine acts only indirectly upon the excretion of carbonic acid by its influence on muscular activity. When the muscular movements were increased by morphine, or when convulsions in animals were produced, the formation and excretion of carbonic acid were greater than in the normal condition ; but if, on the other hand, morphine in- 1 Beitrage zur Heilkunde. 1849. Bd. I. und Zeitschrift f. Hygiene von Oesterlen. Bd. I. Heft 1. 2 Untersuchungen uber die Zersetzung des Eiweisses in Thierkorper unter dem Ein- flusse von Morphium, Chinin und arseniger Saure. Munchen. 1871. und Zeitschrift fiir Biologie. 1871. 3 Ueber den Einfluss einiger Arzneimittel auf den Gasaustausch bei Thieren. Zeitschr. f. Biologie. 1874. pp. 336-372. OPIUM AND MORPHINE. 863 duced muscular inactivity or sleep, the production and excretion of carbonic acid were diminished. The loss of appetite which chronic opium-poisoning creates may depend somewhat upon the paralytic condition of the vessels and nerves brought about by the constant influence of the poison. As to the origin of the neuralgias, anaesthesia, hyperasthesia, and the other symptoms of chronic meconismus, it is explained partly by the general disturbance of nutrition, which leads to fatty degeneration of most of the structures of the body, partly also by the direct influence of the poison upon the substance of the nerves. Results of Autopsies. Characteristic as is the clinical type of opium- and morphine- poisoning, there is very little which is characteristic in the ana- tomical appearances after poisoning cases have terminated fatally. We generally find little change in the alimentary tract, and if we discover, in a few cases, hyperamia of the gastro-intestinal mucous membrane, it is probably due to the antidotes, emetics, etc., employed. On the other hand, we may detect opium in the contents of the stomach by its color and smell. In the heart we usually find dark, fluid blood, but this also is not constant, for the blood is sometimes found coagulated. Hyperemia of the brain and its membranes is most constant; sometimes an accumulation of fluid is found in the subarachnoid spaces and in the ventricles ; sometimes, also, sanguineous effu- sions of greater or less extent in different parts of the brain. The condition of the lungs is also by no means constant. According as death has set in rapidly or slowly, we find more or less pulmo- nary hyperamia and oedema ; we also find, generally, congestion of the liver. The bladder is generally found distended, with urine in which morphine can be detected chemically. All the other anatomical conditions which have been observed are accidental, and not due to opium-poisoning as such. 864 VON BOECK.—VEGETABLE POISONS. Diagnosis and Differential Diagnosis. Poisoning by opiates may be mistaken for acute alcoholism. The history of the case, the absence of alcoholic odor, the odor of whatever is vomited, the absence of alcohol, and presence of mor- phine in the urine, may protect us from an error of this nature. Again, we might confound opium-poisoning with sanguineous apoplexy, or with congestion of the brain, and indeed with all dis- eases which involve increase of intracranial pressure ; the healthy condition of the heart and arteries, the absence of partial paraly- sis of the facial muscles, the equality of the contracted pupils, may enable us to differentiate between them. It is often impossible to distinguish opium-poisoning from poisoning by other narcotics, yet chloroform, ether, hydrate of chloral would betray themselves by their smell, while mydriasis would lead to the diagnosis of poisoning by atropine or hyoscya- mine. The presence of erectio penis would point to opium. In children, opium-poisoning may be confounded with acute hydrocephalus, and in fact such mistakes have occurred; when the history of the case is not to be had, we may be guided to a correct conclusion by the absence of a contracted abdomen, by the nature of the matters vomited, and by the equally and strongly contracted pupils. Prognosis. In general, the prognosis depends upon the quantity of the poison absorbed into the blood. An important prognostic sign is the condition of the pupils; the greater the contraction of the pupils, the more grave is the poisoning ; if they are contracted to the size of a pin's head, we may regard the case as dangerous. The prognosis will also depend upon the question, whether vomiting has occurred spontaneously, or only after the use of emetics, also upon whether the stomach-pump was applied early; it will also be influenced by the condition of the patient's strength. and especially by the state of his heart. During the progress of acute poisoning, the occurrence ot per- OPIUM AND MORPHINE. 865 spiration is to be regarded as a favorable sign. Jardine Murray' mentions that he has observed this in two severe cases of opium- and morphine-poisoning in children. Treatment of Acute Opium- and Morphine-Poisoning. If the poison has been taken in by the mouth, our first duty is to empty the stomach of its contents, so as to prevent the absorption of the poison. The sooner the stomach is emptied, the more favorable the result will naturally be. But this is not only necessary at the outset of the case, but also later on, as morphine and opium often remain in the stomach for many hours. In determining the best method of removing the contents of the stomach, we must be guided chiefly by the length of time which has elapsed since the poison was taken ; if it has been taken quite recently, emetics are advisable. The most effectual of these are sulphate of zinc, tartar emetic, ipecacuanha, and sul- phate of copper. Still, in many cases, vomiting cannot be in- duced by these means, because the excitability of the extremities of the sensory nerves in the mucous membrane of the stomach is so greatly reduced by the narcotic poison that no reflex move- ments can be excited. Tickling the throat also frequently fails to produce vomiting. In such cases we are in the habit of apply- ing mustard poultices to the region of the stomach, of adminis- tering infusion of mustard, etc., in order to restore the excita- bility of the gastric nerves, and thus produce the desired effect. We may, also, as in a case narrated by Moerz, inject apomor- phine subcutaneously, in order to excite central vomiting; this often succeeds when emetics administered internally have failed. I once had an opportunity of observing a severe case of morphine- poisoning, in which apomorphine failed to induce vomiting in a patient who was lying in profound sopor, but the collapse, shortly after the injection, became far more decided than before. Therefore, useful as emetics may be in themselves, we must not forget that, even under the most favorable circumstances, 1 Edinburgh Med. Journ. Feb. 1858. VOL. XVII.—55 S66 VON BOECK.—VEGETABLE POISONS. they may decidedly promote and aggravate the collapse which is imminent in consequence of the action of the poison. For this reason it is preferable to empty the stomach by means of the stomach-pump, as it can be used repeatedly, and does not pro- mote collapse. When emetics can be got to act, they must be administered repeatedly, for it is a matter of frequent experience that even in the third and fourth attack of vomiting, and even later, poison is still found in the matters vomited. Emetics are attended with another disadvantage; in case of recovery, they may ultimately produce violent gastritis, and cer- tain appearances found upon the mucous membrane of the stomach in autopsies are to be attributed to the irritant action of tartar emetic, etc. In the next place, we should attempt, as far as possible, to neutralize by the so-called chemical antidotes the poison which has been introduced before it is absorbed. There are no chemi- cal combinations of morphine which are harmless, yet we can produce some combinations not readily soluble ; as, for instance, its compound with tannic acid, which is only very slowly soluble in the digestive fluids—according to Taylor, about as slowly as pure morphine; but nevertheless tannate of morphine is by no means innocuous. It is therefore desirable in practice to combine the administra- tion of emetics with tannin, or, by means of the stomach-pump, to wash out the stomach with fluids containing tannin, e. g., de- coction of sage, or an infusion of coffee. A method which is sometimes very valuable in order to prevent complete narcosis is the ambulatory treatment; i. e., the patient, supported by two persons, is constantly walked about for hours together. Once coma has set in, this treatment must be avoided, as it might eventually promote respiratory or cardiac paralysis. In the case of little children, it is desirable to prevent their falling asleep by moving them about, or by keeping the air sur- rounding them in agitation; the same effect may be produced by painful stimulation of the skin. If sopor has once set in, we must try, by the administration of stimulants, strong black cof- fee, ether, etc., to keep off paralysis of the nervous centres. If OPIUM AND MORPHINE. 867 respiration and cardiac action begin to be irregular and insuffi- cient, the stimulants must be more frequently administered, and supported by violent cutaneous irritation, cold shower-baths, energetic douches with a full stream, flicking the bare skin with wet towels, etc. If cessation of respiration seems imminent, arti- ficial respiration, either by means of pressure on the thorax or by electric stimulation of the phrenic nerve, may prevent the complete arrest of respiration. Subcutaneous injections of camphor, ether, etc., may perhaps keep up the excitability of the medulla oblongata and of the heart, till the danger is diminished by the elimination of the poi- son. Special mention is due to bleeding and transfusion. Some- times the symptoms present, especially the cerebral symptoms, may indicate the advisability of venesection ; but it must not be forgotten that very little good is done by slight venesections, as the}'' only remove a very small quantity of the morphine rela- tively with the blood, the poison being equally diffused through the whole body ; on the other hand, there is the danger, by with- drawing considerable quantities of blood, of reducing the excita- bility of the respiratory centre and the cardiac muscle, and thus decidedly promoting the onset of acute collapse. Taylor re- marks also very pertinently' that venesection must necessarily hasten the absorption of the poison still remaining in the stomach. It will therefore be advisable, in general, to abstain from venesection, all the more because it possesses only a very limited power of arresting possible cerebral hemorrhage. We find how injuriously bleeding may act in opium-poisoning from a case given by Gallaher,2 in which a lady who had taken two ounces (= 60.0) of laudanum was seized with convulsions after venesec- tion ; as well as from Stafford's case, quoted above, which termi- nated fatally. On the other hand, transfusion of blood might have very favor- able results, especially if it could be accomplished directly from vessel to vessel, at the same time that a depletory withdrawal of blood was going on, as thus more poison would be eliminated 1 Loc. cit. p. 87. 8 Americ. Journ. ApriL 1858. 868 VON BOECK.—VEGETABLE POISONS. from the body, and the fluid remaining in the body would con- tain a more diluted, and therefore less injurious, solution of mor- phine. As far as I know, however, no experimental observations have been made of this mode of treatment, nor has it been tried in practice. Lastly, we must notice the antagonism said to exist between morphine and atropine. The antagonism between these two substances, apart from some hints of it in ancient writings, was clearly stated for the first time by Prosper, Albin and Lebel in 1570,1 and since then it has been repeated from time to time by different authors. Thus Carrignan in 1838, and Graves and Angelo Pom a in 1843, re- peated the assertion. Camus2 was the first to investigate the question experimen- tally, by poisoning rabbits and sparrows with minimum fatal doses of morphine* and then giving them atropine. Three-quar- ters of the animals experimentalized upon died ; rabbits also died in one and one-third hours after the administration of fifteen grains (1.0) of morphine, notwithstanding the subsequent ad- ministration of fifteen (1.0) and four grains (0.25) of atropine ; they even died considerably sooner than if morphine alone had been answerable for the fatal result; hence he concluded that the supposed antagonism did not exist. The animals which he selected for experiment are not the most suitable for this pur- pose, and the doses given are certainly too large ; we might also add that Camus introduced the antidote too early, before the morphine had actually begun to work. Latterly a series of controversial reports have been published for and against the supposed antagonistic effects of atropine in morphine-poisoning ;3 but we cannot draw a decided conclusion from these cases, because either the dose in operation was not known, or the treatment was not purely antagonistic. 1 Frommhold, Ueber den Antagonismus zwischen Opium und Belladonna. Inaug.- Diss. Leipzig. 18G9 ; and Froehlich, Historische u. experimented Beitrage zur Lehre vom physiolog. Antagonismus der Gifte. Pharmacolog. Untersuchungen von Rossbach. Wiirzburg. I. Bd. p. 190 ff. 8 Gaz. hebdomadaire. 11. Aoiit. 1865. 3 See Husemann's Referat in Canstatt's Jahresbericht. 1865. Bd. V. p. 122 ff. OPIUM AND MORPHINE. 869 Some light is thrown on this subject by the researches of S. Weir Mitchell, W. W. Keen, and G. R. Morehouse,1 who, in the LT. S. A. Hospital for Injuries and Diseases of the Nervous Sys- tem, tried experiments with both poisons on sufferers from neu- ralgia, etc., by means of subcutaneous injection, with all the precautions which are possible in human investigations. They come decidedly to the conclusion that no antagonism exists be- tween these poisons with regard to cardiac contraction, or in their action upon the alimentary camd, but that there is an antagonism between their action on the pupils and, in a certain sense, on the brain; the bladder symptom, dysuria, is aggravated by both poisons. Erlenmeyer2 also made experiments on patients, and found that frequency of the pulse is induced by atropine, and not by morphine ; that an antagonism may perhaps exist with regard to respiration, and that a marked antagonism exists with regard to the pupils, as Graefe3 has confirmed. Graefe states that atro- pine produces paralysis of accommodating power ; morphine, on the other hand, causes cramp of the accommodating power, and that the antagonistic action of these two substances affects not only the iris, but also the tensor chorioidea. Harley4 is a pow- erful opponent to the theory of antagonism; he concluded, from experiments on horses and dogs, not only that no general an- tagonism exists, but that the action of morphine is considerably strengthened by atropine, and that morphine is utterly incapable of restraining the action of atropine. The fact that atropine dilates the pupils, while morphine con- tracts them, may have led to the view that the two poisons are antidotes to one another. But even this remarkable action upon the pupils is by no means to be regarded as decidedly one of antagonism. For in animals5 we can succeed in dilating with atropine a pupil which has been contracted by morphine, whereas 1 Hay's Americ. Journ. July. 1865. p. 67 et seq. 2 Berliner klin. Wochenschrift. No. 2. 1866. a Deutsche Klinik. 16. 1861. « Brit. Med. Journ. 1868. March 8 and April 4. 11. 1 Froeldicli, loc. cit. p. 331. 370 VON BOECK.—VEGETABLE POISONS. investigators have generally failed to counteract atropine my- driasis with morphine, as ought to be the case in real antagonism. On the other hand, there are a number of cases reported which seem to intimate that, in the human subject, a real an- tagonism may exist, at least when small doses are in question. (See Atropine.) The consideration of the action of both these poisons upon the heart and its contraction is very important. According to Froelich, minimum fatal doses of morphine mu- riate, administered to the frog, first increase the number of car- diac pulsations, and then diminish them till death supervenes (from cardiac paralysis); this gradual diminution is not inhibited by small or by fatal doses of atropine ; cardiac paralysis appears to set in all .the sooner when both poisons are administered simul- taneously ; but atropine asserts itself so far that it paralyzes the extremities of the vagus ; morphine is quite incapable of arrest- ing the paralysis of the vagus and of the heart established by atropine; on the contrary, it would seem as if the combined action of the two poisons aggravated the cardiac paralysis. It also appears, from the researches of Koning,1 that the simultaneous action of morphine and atropine gives rise to a combined form of poisoning, in which nothing antagonistic is observable, except with regard to respiration; Koning thinks he has observed that it comes less rapidly to a stop from atropine- poisoning when morphine has been subsequently given; this, however, Froelich denies. Reese2 also failed to detect any an- tagonism between the two poisons in experiments on animals; on the contrary, he concludes, from his investigations, that the action of atropine is strengthened by morphine. From a purely physiological point of view, we are now, as Bezold3 has defined it in his theses on atropine and morphine, 1 Over de antagonistiache Wirkung van het Morphium en de Atropine Arnheni 187a 8 American Journ. N. S. 122. p. 373. April. 1873. 3 v. Bezold and Bloebaum, Ueber die Wirkungen des schwefelsauren Atropins. Unter- suchungen a. d. phys. Labor, in Wiirzburg. 1867; Gscheidlen, Ueber die physiolog Wirkungen des essigsauren Morphiums. Untersuchungen a. d. phys. Laborat in Wiirz- burg. 3. Heft 1868. OPIUM AND AlORPHINE. 871 in this position : morphine induces paralysis of all cardiac nerves, of the vaso-motor centre, of the sensory and motor nerves, the paralysis being preceded by a short period of excitement; atro- pine paralyzes the same parts of the nervous system, without, according to v. Bezold, inducing preceding excitement, or, ac- cording to Rossbach, after a brief antecedent excitement. We infer from this that both poisons act in the same manner, and that, though they may appear to be antagonistic in the first stage of their action, as the symptoms of their action differ as to time and intensity, yet finally the action of both poisons is cumu- lative and all the more surely fatal. It is only on respiration that their action appears to be antag- onistic ; at least Gscheidlen asserts that morphine paralyzes the respiratory centre even to the production of apncea, whereas Bezold states that atropine excites this centre, but adds, that in the early stage of its influence this excitement is slightly checked by the action of the pulmonary portion of the vagus. Erlen- mayer also observed as a result of the administration of atropine in human subjects, increased frequency of respiration; he found also that, when both poisons were given, the respiration was not materially altered. The question, whether there is any antagonism as to their effect upon the brain, is answered in the affirmative by Weir Mitchell, Keen, and Morehouse, who succeeded in neutralizing or at least alleviating the sopor induced by opiates in the human subject, by subcutaneous injection of atropine ; in the same way morphine moderated the symptoms of atropine in the human subject. These investigators employed one-thirtieth of a grain of atropine to each one-quarter of a grain of morphine (1: 7|). According to Dodeuil,1 four parts of morphine are rendered innocuous by one part of atropine. No one will care to try larger doses than these. Murdoch2 witnessed the rapid recovery of a woman who had taken one and a half drachms (=6.0) of laudanum, upon the subcutaneous injection of one-quarter of a grain (=0.015) of atropine, two hours later; dilatation of the 1 Bull, de Therapeut. p. 275 ff. 1865. 2 New York Med. Record. Oct 343. 1871. 872 VOX BOECK.—VEGETABLE POISONS. pupils after half an hour; return of consciousness after several hours. The excitability of the sensory nerves is distinctly reduced by both these poisons, and, according to Erlenmayer, in a greater degree by both combined than by one alone. Neither is there any antagonism with regard to their action on the alimentary canal; morphine fails to diminish the dryness of the throat, which is a constant symptom of atropine-poisoning, and the vomiting which so often follows morphine is not checked by atropine, as all investigators unanimously admit; according to the statements of the Americans, it is increased : so that, for instance, emetics which have been given in cases of morphine- poisoning, do not begin to act till atropine is administered. Both poisons also agree in inducing dysuria. But although from the physiological point of view we can- not admit an actual antagonism between these substances, and although in experiments on animals no favorable results have been obtained, yet we have a large number of cases reported which show that atropine can be used with advantage in mor- phine-poisoning. Although the great majority of clinical reports on this subject are not absolutely clear and conclusive, yet it would, I think, be too sceptical to shut one's eyes entirely to these facts. Still, there is always a difference between a useful remedy and an antidote in a case of poisoning. If we believe that morphine causes death by reducing the excitability of the respiratory centre to the extent that even excess of carbonic acid in the blood cannot stimulate it to develop the necessary respiratory movements, and that con- sequently death by morphine is death by carbonic acid, it is not incomprehensible that atropine, by virtue of its influence upon respiration, should partially counteract the effects of mor- phine. Naturally, if morphine is absorbed in sufficient quan- tity to cause cardiac paralysis, atropine can be of no avail ; we have also to guard against giving atropine in doses which might themselves induce cardiac paralysis, or even in doses which, when combined with morphine, would complete the car- diac paralysis. OPIUM AND MORPHINE. 873 It is possible that atropine might, for a time, be as useful as artificial respiration. We may be allowed to quote a case in point, out of the many.1 H. S. Schella relates an attempt at suicide by poisoning, in which a young lady, having taken one and a half ounces (= 45.0) of laudanum, had lain for one and a half hours in deep coma; the stomach-pump and emetics had been tried in vain. Thirty drops of tincture of belladonna were administered internally, then one-forty-eighth of a grain (= 0.00125) of atropine injected subcutaneously, upon which the respiration, which was rapidly failing, and the pulse, which was almost extinct, became again observable. Vomiting followed, and her condition improved ; two similar injections were again given; vomiting and improvement again followed ; finally, the patient recovered. A case of a man who was poisoned with two ounces (= 60.0) of laudanum is com- municated by Thomas Thatcher Graves,3 in which no vomiting occurred ; the doctor, who did not see to the case for two hours, threw into the patient's throat one drachm (= 4.0) of tincture of belladonna, whereupon he almost immediately (!) was so revived that he was able to speak and to take another spoonful of the tincture himself. The pupils became dilated, and after two hours recovery set in. We may give small quantities of atropine, either in the form of tincture or extract of belladonna, or atropine itself may be given either internally or subcutaneously. Very large doses of atropine have, however, been tolerated in morphine-poisoning, as, among others, Carter's4 case proves, in which twelve consecutive injections of atropine were made, which altogether contained about three-eighths of a grain (0.025) of the alkaloid. The case ended in recovery ; the dose of opium taken was not known. 1 Frommhold, loc. cit., quotes from medical literature eighteen cases of atropine-poi- soning with morphine treatment, and fourteen cases of morphine-poisoning with atro- pine treatment, which ail terminated favorably, although in most cases very large doses had been taken. 2 Philad. Med. Times, p. 134. 1872. 3 Boston Med. and Surg. Journ. 1872. 24. Oct. 4 Philad. Med. Times. May 1. p. 277. 1871. g<74 VON BOECK.—VEGETABLE POISONS. All authors are agreed that the first effect of atropine is dila- tation of the pupils, which often sets in after one-quarter or one- half an hour, but sometimes it does not appear for several hours; this may be due to slower absorption into the circulation so much reduced by the morphine. The value of the atropine treatment of opium- and morphine- poisoning may perhaps be approximately estimated by the state- ment of Johnston,1 that out of seventeen cases of opium-poison- ing which he witnessed, eleven recovered under atropine treat- ment, while six died. That there are cases which end fatally in spite of atropine treatment, is evident not only by Johnston's cases just quoted, but by a number of other cases on record.8 In a case communi- cated by John Ogle,3 a man fifty-five years of age, who had taken an ounce (= 30.0) of laudanum, died in twenty-seven hours, in spite of the administration of twelve and one-half grains (= 0.75) of extract of belladonna. Instances are not wanting4 in which the symptoms of mor- phine-poisoning were so aggravated by atropine that its use had to be discontinued. These cases, however they may negative a true antagonism in atropine, do not take from it all value as an antidote, and they are quite reconcilable with the physiological facts. Even very severe cases of poisoning may be cured by simple treatment without the use of atropine, as, among many cases, that of Bergsten5 proves, in which an apothecary's assistant took six grains (0.4) of morphine acetate, and notwithstanding the most violent symptoms, recovered under treatment with strong coffee, cognac, and the stomach-pump. Chatanionti also gives a case in which recovery set in after poisoning by five drachms (twenty grammes) of laudanum, without the use of atropine, although vomiting did not come on till after seven hours. In 1 Med. Times. 1872 and 1873. 8 Robert Broolcs, Philad. Med. Times, p. 708; and others. 1873. 3 Med. Times and Gaz. Oct. 3. 1863. * E. g., Todd, Americ. Journ. of Med. Sciences, p. 131. 187:*. 6 Upsala Lakareforen Forhandlingen. VII. p. 647. 1872. 9 Gaz. des Hopit 1873. p. 32 OPIUM AND MORPHINE. 875 such cases, however, we must guard against a false conclusion, and not take a post hoc for a propter hoc. Other remedies have been recommended, such as inhalation of oxygen,1 subcutaneous injections of whiskey, veratrine,11 etc., quinine8 internally, prussic acid' internally or in enemata, castor oil.6 Treatment of Chronic Opium-Poisoning. Chronic opium-poisoning, opiophagy, etc., morphioenesis, be- longs to the category of diseases which are almost incurable, just because the cause of it is generally not far to seek. The weaning from the use of opium or morphine is a laborious task for the patient, as for the physician, and yet upon it rests the only hope of recovery. If such patients are suddenly deprived of the enjoy- ment of the drug which is poisoning them, they sink into a miserable condition, the most dangerous symptom of which is collapse. They look ill and emaciated, their eyes are heavy, their respiration is labored, they suffer from dyspncea, anxiety, cardiac palpitation, frequenc}'" of pulse up to 120 in the minute, tendency to perspiration, great irritability, dysuria, pains in all possible nerve-regions, especially in the stomach and intestine, want of appetite, thirst, diarrhoea, absolute sleeplessness. This condition may terminate in death, if the use of the drug is not resumed. Physicians are not agreed as to whether opium ought to be withdrawn suddenly or gradually from such persons. According to my experience, the most effectual plan is to arrest the habit suddenly, with one stroke, if we have to do with toler- ably hardy individuals; they are not subject to collapse, espe- cially if a large quantity of wine is given to them. Fleming," who defends this view, advises that these patients should be given 1 Farrington, Philad. Med. Times, p. 743. 1873. 3 Todd, loc cit 3 Kersch, Memorabilien. 1. 2. 4 Blank, Rev. de Therap. m6d. chirorg. 17. 1857; and Shearman, Med. Times and Gaz. March 7. 1857. s Lancet. 1868. Sept 2 cases. 6 Brit Med. Journ. 1868. Feb. 18. 37 beats and yet could not bring it lower than 64 in the minute. Nickel also mentions that he saw the pulse sink by 20 to 24 beats. This retardation of the heart-stroke, as Gibbon3 asserts, reaches its climax about half an hour after the ergot has been intro- duced. In more severe cases stupefaction, sopor, and retention of urine set in, and with the continuance and aggravation of these symptoms death may supervene, all the more surely be- cause not only the frequency of pulsation, but the general action of the heart, is reduced. All investigators are agreed that the arteries are less filled, and become lax and easily compressible. Dyspncea, etc., follows upon this diminution of the decarboniz- ing of the blood, and may easily cause death, though a fatal result is among the exceptions. More rarely neuralgic pains are observed in different organs, especially in the fingers, and in the skin, where the nervous affection takes the form of intolerable irritation. In some cases the muscular weakness may continue some days after the poisoning ; also actual aberration of intellect is said to have occurred after ergot-poisoning. If the poison has been taken by pregnant women with the intention of producing abortion, they sometimes attain their ob- ject, especially if the pregnancy is far advanced; in the earlier months ergot fails to produce this effect. The character of the symptoms of ergot-poisoning may be more or less modified by the occurrence of the premature birth. The course of the symp- toms produced by ergot is generally tolerably rapid. Analysis of Symptoms—Character of Acute Ergot-Poisoning. The most evident symptoms in the early stage of the action of ergot-poisoning—retching, vomiting, diarrhoea, and salivary Recherches sur les proprieties du seigle ergote et de ses principes constituants. Gaz. med. de Paris. Nos. 31-33. 1846. - Beitrage zur Pharmacodynamik. Bayr. Corr.-Blatt. No. 44. 1860. B The Sedative Powers of Ergot. Amer. Journ. of Med. Sciences. Jan. 1844. EBGOT. 895 secretion—are consequences of the action of the poison on the sensory nerves of the mucous membrane of the alimentary canal; these are excited by the poison, and the excitement is commu- nicated to motor and secretory regions—reflex action. This explanation avails at least for these symptoms when they set in soon after the introduction of the poison. The vomiting which sometimes occurs in the later course of the poisoning is, perhaps, traceable to an action of the poison on the central nervous system; in the same way the subsequent diar- rhoea is dependent on the influence of the poison on the vessels and the distribution of blood. We have no accurate knowledge as to the origin of the flow of saliva. In all probability it is to be regarded as a reflex salivation, as it follows upon eating acrid substances, and precedes vomiting. The vomiting, dependent on the same cause, is connected with the early stage of muscular weakness. The muscular exhaustion continuing for a longer time is on its side produced by the changes effected in the circu- lation by the poison. We can only suggest hypothetical ex- planations of the action of this poison on the brain; we possess no certain knowledge on the subject; only this much may be said with some confidence, that here also the alteration in the circulation may exert a considerable influence. The chief effect of ergot and its preparations is over the organs of circulation, the heart and the blood-vessels. The diminution of cardiac pulsa- tions, and general lowering of cardiac action, possess the first claim to our consideration. The statements of Felix von Wille- brand of Helsingfors' are very noteworthy, to the effect that the healthy or even the hypertrophied heart contracts under the influence of ergot, so that this diminution of volume may be clearly diagnosed by percussion when the poison has ceased to act; this contraction is naturally followed by a dilatation till the status quo ante is reached. With regard to experiments on animals, all investigators agree that with them, as with the human subject, a diminution of the frequency of the heart- • Notisblad for Lakare och Pharm. 1858. Nos. 10 and 11; Schmidt's Jahrb. Bd. 108 p. 299 ; Rossbach's pharmac. Untersuchungen. I. Bd. p. 116. 896 VON BOECK.—VEGETABLE POISONS. stroke is produced by ergot and its different preparations. See Haudelin, Briesemann,1 Eberty,2 Rossbach,3 and others. Eberty brought the frog's heart to a stand-still in diastole by injection of large doses of ergotine into the gastric vein ; he traces this effect to irritation of the extremities of the vagus. Rossbach observed some very remarkable movements in his ex- periments with different preparations of ergot on the hearts of frogs. The pulsations of the ventricle diminished in frequency, those of the auricles remained steady; the filling of the ventri- cle was incomplete, the contraction of the separate fibres of the cardiac muscles not simultaneous, but alternating, so that fre- quently a sort of peristaltic movement in the heart was observ- able ; certain bundles of muscles remained for a long time in a state of contraction, while neighboring groups were relaxed. These and similar movements were observed by Wernich 4 also. Rossbach traces this action of the preparations of ergot (he used Wiggers's ergotine, and Wenzell's ecboline) to an influence exer- cised by them upon the cardiac muscular apparatus, which, as a peculiarly constructed muscle, may even in a physiological sense be regarded as other than a common striped muscle. It is cer- tain that we are not greatly assisted in our attempts to explain the action of ergot on the heart by supposing it to act on the cardiac nerves. Wernich, on the other hand, traces the changes in cardiac contraction not to direct influence of the poison upon the heart, but regards them as secondary symptoms, dependent on the action of ergot and its derivatives upon the vascular system. The chief effect of ergot is certainly upon the vascular system. It is a fact that the arteries are contracted; these changes may be somewhat considerable, so that vessels of rather large dimensions appear as very narrow ones with thick walls. This 1 Microskop. Untersuchungen iiber die Wirkung des Digitalin, Veratrin, und Ergotin auf die Circulation. Dissert. Rostock. 1809. 2 Ueber die Wirkung des Mutterkorns auf die Herzthatigkeit und den Blutdruck Dissert. Halle. 1873. 3 Pharmacologische Untersuchungen. Bd. I. p. 214 ff. 4 Einige Versuchsreihen uber das Mutterkorn. Berlin. 1874; and Virch. Arch. Bd. LXI. 505. ERGOT. 897 contraction chiefly affects the small arteries, but even in the larger ones it is clearly recognizable. On the other hand, there is a dilatation of the veins. The condition necessarily attending these changes is a diminished quantity of blood in the contracted arterial system, and a corresponding increase in the contents of the veins. This fact may be directly observed in frogs as well as in rabbits, and was observed by Wernich not long ago with the microscope in the web of the frog, and was drawn by Holmes by means of the camera lucida, and micrometrically measured by Briesemann.' Clinical experience of the action of ergot in lowering the cir- culation of the blood entirely corresponds with this. This lower- ing action is an indisputable fact for the practical physician who has employed this drug, even though the direct experiments made on animals have been questioned from various quarters. The main question connected with this circumstance is how this vascular contraction of the arteries is brought about. It was formerly assumed that ergot caused contraction of the arterial vessels by stimulating their muscular coat, so that they were in a state of active contraction. This contraction of the arteries was then further traced to an influence which ergot was supposed to exercise upon the vaso-motor centre. A true cramp of the arte- ries was therefore regarded as the effect of ergotine, a cramp that under some circumstances might last long. A considerable shock has been given to this view of ergotine action, universally prev- alent till quite lately, from the circumstance that the increase of blood pressure to be postulated a priori from so strong a con- traction of the arteries has not been found by any of the later investigators, except Eberty, in their experiments on blood-pres- sure with the kymographion. Thus Holmes,2 Haudelin, Her- mann, and Wernich found almost constantly a more or less con- siderable decrease of blood-pressure. The diminution of blood- pressure directly contradicts an active contraction of the arterial vascular system ; again, as Wernich shows, such a contraction is disproved by the beneficial influence on arterial aneurisms, 1 Dissert.- inaug. Rostock. 1869. 2 Effets de l'ergot du seigle. Arch, de Phys. 1870. VOL. XVII.— 57 898 VON BOECK.—VEGETABLE POISONS. which Langenbeck, Hermanides, and others produced by ergo- tine injections; lastly, it is opposed by Willebrand's observa- tions, mentioned above, with regard to the diminution of volume of the heart. The question which must next arise is : How, then, is arterial contraction induced? If it is not active, it must be passive. The heart must in a given space of time pump less blood into the periphery than in its natural condition, because less blood is conveyed to it by the systemic and pulmonary veins ; there must be an unwonted accumulation of blood in the veins. Such an accumulation of blood in the veins is only pos- sible by a diminution of the tone of the veins, as Wernich insists. This dilatation of the veins, this increased amount of blood in them, can be directly proved. According to Wernich's observa- tions, it is the veins of the mesentery, of the uterus, of the blad- der, of the abdominal veins generally, which show most clearly this engorgement after the introduction of ergotine. Wernich draws a parallel between the symptoms of ergotine-poisoning in frogs and those which Goltz has observed in his experiments on pulsation with regard to the circulation. In both cases there is a strongly marked arterial ansemia, and an equally striking ve- nous hypersemia; in both cases there is a diminution of cardiac contraction leading to entire cessation of cardiac action ; in both cases Wernich sees in the dilatation of the veins the primary, in the contraction of the arteries and in the action of the heart the secondary symptom ; the arteries, therefore, collapse from want of sufficient quantity of blood, the action of the heart proceeds more slowly or ceases altogether from diminution or entire cessa- tion of the supply of blood to it; so that the action of ergotine appears to lead to an accumulation of blood in the veins. The cause of this decrease of the tone in the smooth muscles of the veins has not been experimentally established with sufficient accuracy. It should be mentioned that Zweifel, in the treatise above quoted, comes to the conclusion, from careful experiments, that not only ergot and its preparations, but a whole series of substances, produced arterial contraction, and that all these sub- stances have one property in common, that of producing consid- erable pain when subcutaneously injected. He therefore regards the action of ergot on the vessels as by no means its chief action, ERGOT. 899 but believes that to consist in its influence upon the central ner- vous system. A few words will be sufficient as to the influence so often maintained and so often denied of ergot of rye on the action of the uterus, as changes in this organ are not among the most im- portant symptoms in acute poisonings. For the accoucheur the fact is established that ergot may increase pangs already exist- ing, although many maintain that it cannot originate them. Yet it has been proved by various investigators, especially recently by Schlesinger and by Wernich, that even in the unimpregnated uterus of animals, movements take place under the influence of preparations containing ergotine. But these movements, accord- ing to our present experience, as they respond to the physio- logical experiments of the investigators above-mentioned, may be regarded, not as primarj' effects of the poison, but as secondary and dependent on the arterial ansemia produced by ergotine, etc. Wernich's experiments appear to me here again to be valuable ; according to them, in experiments on animals, as a rule, the change of the calibre of the vessels does not influence the dis- coloration and blanching of the uterus till first movements of the uterus have been observed, of short duration and moderate in- tensity, but still so evident, that there is no doubt of their exist- ence. It is therefore sufficiently clear that it is not the arterial ansemia or venous hypersemia alone which causes these move- ments. On the contrary, it might almost be assumed that the influence of ergot upon the movements of the uterus proceeds solely from an influence of the poison upon the nerve-centres of these movements in the lumbar region of the cord and in its higher-situated parts, as well as in the brain. But even in this case some influence might be attributed to anamiia, induced by the ergot; only when we come to further reflect on the action of the poison on the spinal cord, the hypothesis of a direct action of the poison is much more simple, although the whole question appears as yet to be far from settled in one direction or the other. The experiments of Schlesinger and Oser' would go to prove, firstly, that the arterial ansemia is to be regarded as the stimu- ■ Wiener med. Jahrbiicher. 1872. I.; and Schlesinger, Ibid. 900 VON BOECK.—VEGETABLE POISONS. lating cause of the movements of the uterus ; and, secondly, that the uterine contractions are caused by excitement from the cen- tral organs. In this experiment the exclusion of the flow of arteriaf blood to the brain, by ligaturing all the blood-vessels leading to the brain, produces in about half a minute general contraction of the uterus. The abortions produced by ergot- poisoning are thus accounted for by its increasing uterine con- tractions. The hypothesis that the uterine contractions are produced by alterations in the distribution of the blood might be thought to be supported by the experiments of S. Mayer and Basch, which show that arterial ansemia of the intestine stimulates it to violent peristaltic contraction. This circumstance accounts for the diar- rhoea which sometimes sets in even in the later part of the course of poisoning by ergotine and ergot of rye. The action of ergot on the brain and the spinal marrow is not very marked in the human subject, but may be more accurately ascertained by experiments on animals. Ergotine, injected in sufficient quantities into frogs, paralyzes voluntary movements as well as reflex actions. Zweifel regards the influence of ergot upon the brain and spinal marrow, which it paralyzes, as its main action. The paralysis begins at first in the hind legs and advances continuously forward ; the limbs recover their power in the same sequence. With moderate doses the whole frog may be paralyzed, so that only cardiac and respiratory contractions continue. In mammalia also ergotine produces a remarkable unsteadiness of gait and general paralysis which lead to death. The spinal cord is therefore affected by the active principle of ergot; it is stimulated for a short time and then paralyzed, and this paralysis may, when the doses are sufficiently large, extend even to the centres of respiration and cardiac contraction. It appears very probable, from some symptoms in chronic ergotine-poisoning, that this substance exerts some influence on the sensory nerves, but it has not yet been determined satisfac- torily by experiment. The symptoms seem to imply a primary stimulation and subsequent paralysis of the sensory nerves. A few words must be added as to the influence of ergot upon the foetus in utero. The influence of this drug upon the child ERGOT. 901 has been over-estimated. It has been asserted that the number of still-born children is increased by the administration of ergot; further, it has been stated, as the result of observation, that the pulsations of the child are diminished in frequency by the mothers having taken ergot; finally, the contractions of the uterus are said to injure the child by compressing its body.1 All these observations have been questioned in recent times, and no accoucheur hesitates to make use of this drug if the symptoms indicate its administration. In the same way the effect of ergot in producing abortion has been considerably exaggerated. It very seldom succeeds in expelling the foetus, if the conditions for its expulsion have not arisen in some other way. In conclusion, it must be stated that there is perhaps no poi- son respecting which our knowledge rests on so comparatively weak a basis as this ergot, and that we can only succeed in obtaining really satisfactory information on the subject when it has become possible to prepare the active principle of ergot as a pure substance. Till that time the preparations offered for sale, as well as those prepared by particular investigators (such as Wernich and Zweifel) will differ from one another in their effects. Results of Autopsies in Acute Ergot-Poisoning. Reports of autopsies in the case of persons who have died of acute ergotism are extremely rare. In Richter's case, quoted above, respecting a young woman, twenty-three years of age, in a state of pregnancy, in whom the expulsion of the foetus, six to seven months old, actually did take place, the observations at the autopsy were considerably modified by the violent hemor- rhage, probably fatal, which occurred during that act. Injection of the vessels of the mucous membrane of the oesophagus and the stomach and a few corroded spots were found; small portions of ergot which had been taken were found still in the stomach, and were proved to be such, both microscopically and chemi- cally. In dissection of animals poisoned with ergotine we gene- > Beatty, De 1'influence du seigle ergote sur le Foetus dans la matrice. Journ. des Connaiss. med. Feb. p. 135. 1845. 902 VON BOECK.—VEGETABLE POISONS. rally find highly marked venous engorgement, especially in the abdomen, and above all in the urinary bladder, which is generally distended. But, according to Zweifel's reports, the bladder is sometimes found empty and contracted. What has been written about hyperemia of the brain and its membranes is to be re- garded as at least very uncertain. Diagnosis and Differential Diagnosis. The diagnosis of acute ergot-poisoning rests chiefly on the history of the case and on the probable discovery of small par- ticles of ergot in the vomited matters and in the fseces. When ergotine has been administered, especially in the form of sub- cutaneous injection, the diagnosis of ergotine-poisoning presents formidable difficulties. Diminished frequency of cardiac pulsa- tions, contraction of the arteries, reduction of the temperature, etc., might afford some clue. But none of these symptoms are characteristic enough to exclude with certainty the possibility of other poisonings. Prognosis. It has been already stated that acute ergot-poisoning very seldom ends fatally. The prognosis will be the more favorable the more normal the action of the heart before the introduction of the poison, the earlier the occurrence of vomiting, or that a suitable system of treatment was commenced. Treatment. The first indication in internal poisoning by ergot and its pre- parations is the elimination of the contents of the stomach by means of emetics; later on purgatives may be administered to remove the poisonous substances which may be lodged in the intestinal canal. As chemical antidotes for counteracting the effect of the poison introduced, tannin, and substances contain- ing tannin, are the most effective. As to the rest, the treatment must be limited to combating the symptoms produced by the ERGOT. 903 poison. The principal of these is cardiac asthenia, which requires energetic treatment. Alcohol, ether, camphor, preparations of ammonia, wine, coffee, etc., are the best means of arresting threat- ened cardiac paralysis. Perhaps nitrite of amyl is a remedy which, by dilating the arteries, may check the supposed accumu- lation of blood in the veins. At present we have but few obser- vations to help us. Changes which Ergot undergoes in the Organism.—Tests. So long as the chemical properties of the active constituent of ergot are not accurately known, and so long as it cannot be iso- lated in a state of purity, we cannot say what are the changes which it undergoes in the animal organism; and it is equally impossible to venture a positive statement of the mode in which it is excreted. That the active principle of ergot passes into the blood and becomes active there is evident from observation of the symptoms which it produces, while the fact that the subcuta- neous injection of ergotine rapidly induces its special action may be advanced as experimental confirmation. Should it be neces- sary, for judicial purposes, to test for poisoning by ergot, the only basis we have to go upon is the discovery of the remains of the powder of ergot in the matters vomited and in the fseces. As far as our knowledge goes such a test has only once been fur- nished (in a case ending fatally, which Xeubert has reported), by heating the organic substances suspected to contain the poison with alcohol, and then evaporating the alcohol; a residuum was obtained very similar to Wiggers's ergotine, and possessing its qualities, viz.: insolubility in alcohol, ether, and acetic acid, sol- ubility in water only when in combination with mucus, an un- pleasant odor, and sharp, bitter taste. Chronic Poisoning by Ergot. The long-continued use of ergot, especially in the form of flour, and bread made of flour, often led, in former ages, to fear- ful devastation of whole races of people, inhabiting more or less 904 VON BOECK.—VEGETABLE POISONS. extended tracts of country. The first reports which we possess on this subject date from the ninth century; it is not, however, till later years that we meet with good descriptions of this malady, which fix upon it the undoubted character of chronic ergotism. In the year 1630 Thuillier discovered the cause of this affection, which had till then been attributed to all possible and impossible factors, among which mystic views played the chief part. Diseases produced by the consumption of food containing ergot appeared in the middle ages as very violent epidemics; but they did not cease, even after the cause of the disease was known ; from time to time—often after intervals of ten, twenty, thirty years, and longer—epidemics broke out again, which gen- erally lasted only a year, but sometimes continued through several years; thus, for instance, an epidemic was observed in Switzerland which lasted from 1709-1716. Epidemics more or less severe continued to prevail in the last century ; several are recorded even in our own century, and though they may not be equal in extent of distribution to former ones, still they warn us of the possibility that what happened as late as thirty }Tears ago, and even more recently, may occur again under favoring condi- tions. And therefore we may be permitted to say a few words here on the subject of chronic ergot-poisoning. As above men- tioned, chronic ergotism appears in two clearly distinct forms; one form is characterized chiefly by the presence of convulsions, with considerable disturbance of sensation ; it is therefore called spasmodic ergotism or " Kriebelkrankheit;" the second form is characterized by gangrene of the face and the extremities, and is therefore called gangrenous ergotism. Spasmodic Ergotism. Etiology. In Falck's1 treatise on poisoning we find accounts of nineteen epidemics of "Kriebelkrankheit," which appeared chiefly in 1 Handbuch der speciellen Pathologie und Therapie von Virchow. Bd. II. 1. Abthlg. pp. 319, 320. ERGOT. 905 Germany, between the years 1556 and 1795. All these epidemics began in the autumn of each year, and generally lasted till the next year, often till the following autumn. They always ap- peared after corn-harvest in bad and rainy seasons, which were distinguished by failure of crops, ft was long unknown what was the poisonous constituent of the flour, but it has now for many years been ascertained with absolute certainty that it is the presence of ergot, while other plants, such as the Lolium temulentum, which some regarded as the cause of Kriebelkrank- heit, have been shown to have no connection with it. The wheat which gave rise to this affection always contained a large propor- tion of ergot, at least one-tenth, sometimes even one-eighth of the whole quantity, as Johann Taube * and Anton Scrinci have shown. The circumstance that only those were attacked who had partaken of bread or other food prepared from wheat con- taining ergot, and the fact that they improved when they ate bread containing no ergot, and relapsed when they returned to the ergotized wheat again, proved incontestably that ergot was the sole cause of the disease. The disease attacked the lower orders rather than the higher, as they are the largest bread-con- sumers ; neither age nor sex was spared, but babes at the breast were never attacked. The following reports show that even in our own time we are not quite free from this malady. Aschoff2 describes a house epidemic, which in the very damp autumn of 1840 appeared in a family consisting of eight persons ; the illness lasted in each case from three to five weeks, and two children, seven and eleven years of age, died of convulsions on the twenty-first day of their illness. Ditzel3 describes twenty-four cases of morbus cerealis in that same year, all of which ended in recovery. Puchstein * reports the cases of five persons who were attacked with " Krie- belkrankheit" in the village of Stregow in the district of Kamin. 1 The older reports of this disease, chronologically arranged, are included in Falck's work, above cited. 2 Zur Lehre von der Kriebelkrankheit. Casper's Wochenschr. Oct. 1844. 3 Nachtheilige Wirkung des Mutterkorns. Oppenheim. Zeitschr. Miirz. 1844. 4 Beitrag zur Geschichte der Kriebelkrankheit. Med. Zeitg. des Vereins in Preussen. No. 2. 1853. 906 VON BOECK.—VEGETABLE POISONS. The circumstance that the disease was limited to the members of a shepherd's family, while his neighbors remained free, is attrib- uted by Puchstein to the fact that the neighbors had mixed the flour containing ergot with a quantity of potatoes and barley, whereas the shepherd's family had eaten it unmixed. Heusin- ger ' gives a report of an epidemic in the village of Mollnau in Upper Hesse, which lasted from the autumn of 1855 till the sum- mer of 1856. The ergot of brome-grass was the main cause of this epidemic. L ngefug2 also describes an epidemic in a fam- ily at Darkemen, in the year 1845, to which one person suc- cumbed. A similar epidemic in the neighborhood of Holzmin- den is mentioned by Pockels.3 Lastly, we have a report by Dr. Flinzer4 of an epidemic at Auerbach, near Stolberg, in Saxony, in the year 1867, in which there were some deaths. In 400 parts of rye there were 40 parts of ergot; therefore ten per cent. The epidemic attacked a farm-house with six inhabitants. Symptoms and Course of Spasmodic Ergotism. When flour strongly impregnated with ergot in the form of bread or other farinaceous food has been eaten for several con- secutive days in some considerable quantity, the first symptom of ergot-poisoning makes its appearance in the form of a peculiar irritation of the cutaneous nerves, much like the sensation of an ant creeping over the skin ; this feeling is called in German "Kriebeln," hence the name of "Kriebelkrankheit" given to the disease in this country. As to the point of time at which this sensation sets in, cases are known in which the first symp- toms appeared as early as the fourth day of partaking of the bread or the flour containing ergot (Flinzer). Yet in some cases it may be borne longer without inconvenience. This depends on the quantity of ergot introduced, and on the relative proportion of bread to it, as also on the quality of ergot itself. It is an 1 Deutsche Klinik. No. 20. 1856. 2 Casper's Vierteljahrschrift fiir gerichtliche Medicin. etc. Bd. IX Hft. 1. 1S56. 3 Deutsche Klinik. 1. 2. 1857. 4 Vierteljahrschr. f. gerichtl. Medicin. VIII. 2. p. 360. 1808. ERGOT. 907 ascertained fact that this substance in growing old loses its activity and poisonous character, and that it is also deprived of some of its activity by the process of grinding the wheat into flour, and baking the flour, etc. Thus there is a case reported in which several persons consumed in five days twenty-two and a half pounds of ergot in bread without suffering in consequence ; whereas, if the same quantity had been taken in a fresh condition, death must have been the inevitable result. This formication con- tinues during the whole course of the illness, and is the last symptom which disappears. It affects chiefly the fingers and toes, but may also extend to other organs, e. g., the hands and arms. In some cases the formication increases to actual numb- ness, and even to complete anaesthesia of the parts affected. Simultaneously with this formication symptoms set in in the stomach and intestinal canal similar to those described under Acute Ergot-Poisoning. Vomiting and diarrhoea alternate with violent colicky pains ; curiously enough, as a rule, this is ac- companied with intense hunger. The patients suffer from insatiable hunger, to satisfy which they devour everything eatable that comes in their way. On account of this symptom, the disease has been entitled Haphania, which name arose out of the mistaken supposition that the wild radish (Raphanus raphanistrum) was the cause of the disease ; now it is used as a synonym for ravenous hunger. Another symptom usually present is a peculiar sensation of discomfort, anxiety and weariness, giddiness, and general uneasiness ; the patient also complains of distressing pressure in the pit of the stomach, and the formication grows into very acute pain. Then we get involuntary twitchings in various groups of muscles, e. g., in the tongue and in the extremities. These twitchings soon pass into continuous contractions, which specially affect the flexors, so that the arm, e. g., remains fixed in a bent position. This muscular cramp will last a variable time, half an hour or even a whole hour, or more ; this cramp is also very painful; from this symptom the disease was formerly called in Germany udie ziehende Seuche," " der krumme Jammer," " die Schwere- nothkrankheit," etc. The retching and vomiting are persistent, but the action of the bowels is sluggish. When the contractions 908 VON BOECK.—VEGETABLE POISONS. pass off, a state of utter exhaustion remains. But soon the pain- ful convulsion returns and makes the patient moan and groan continuously. The contractions now appear simultaneously in various groups of muscles, the epigastrium is tightly distended, the facial muscles are distorted, the legs are flexed. At the same time, the hands frequently assume a beak-like form, the fingers being contracted towards the middle finger, and simultaneously flexed towards the ball of the thumb ; the foot assumes a similar form. The pupils are usually contracted, sometimes distorted; the eyes are fixed. The skin is covered with cold perspiration, the urinary excretion is suppressed; but at the same time there is violent dysuria, dependent on spasm of the bladder. The pulse is weak and low. In severe cases the patient loses the power of sight and speech, of hearing and consciousness. Delir- ium sets in, the face is pale and sallow, the head, like the body, feels cold, and thus, with the continuance of the convulsions, and gradually advancing cardiac paralysis, death may super- vene. This may occur as early as the third day after the begin- ning of the symptoms, especially when the contractions, as sometimes happens, attack the respiratory and spinal muscles, inducing opisthotonus. The loss of sight may be preceded by all possible visual disturbances, colored vision, double vision, etc. In many cases which do not terminate fatally, cataleptic and epileptic attacks occur, either with or without loss of con- sciousness. Of the other organs, the skin is especially under the influence of this poison. Besides very abundant perspiration, pustules often break out, or even larger furunculi. The exanthemata sometimes resemble scabious eczema; they appear in the later stage of the malady, as, e. g., in Aschoff's case, fourteen days after the appearance of the first symptoms of poisoning. But other disturbances of nutrition in the peripheral organs are also reported, as, e. g., whitlows on the fingers, occurring as late as the fourth and fifth week, and diseases of the finger-nails, which are encircled by a dark ring. Cardiac contractions are generally slow and feeble, the arteries are constricted and contain little blood. The respiration is very labored during the spasms, but tolerably regular in the free intervals. When death supervenes, ERGOT. 909 it is usually not till after a fortnight or later; the convulsions may have ceased, yet loss of sight and hearing with violent head- ache, stupor, and delirium, may set in, attended with diarrhoea; and thus the fatal stage may assume the form of typhus and general collapse. Death is generally ushered in by either con- vulsions or paralytic symptoms. The whole form of the illness, therefore, is very variable, and its course highly irregular. The illness may last 4-8 weeks, and even longer. If the case takes a favorable turn, the spasms diminish in number and intensity, the disturbances in the functions of the organs of the senses gradu- ally subside, digestion recovers its tone, and complete recovery may set in, though not for several weeks. In many cases, how- ever, recovery is incomplete, various pains and infirmities remain behind, especially, e. g., muscular weakness and tremor, stiff- ness in the joints, in other cases actual paralysis and epileptic attacks ; in some rare cases melancholia and imbecility are results of this disease ; permanent disturbances of visual power are also reported. Analysis of Symptoms—Nature of the "Kriebelkrankheit." The symptoms which mark the course of spasmodic ergotism all point to a disturbance of the central nervous system under the influence of ergot: the motor as well as the sensory centres in the brain and spinal cord are first excited, and later on para- lyzed, by the poison. There can be no question that the convul- sions,' the disturbances in the organs of the senses, in the sen- sorium and in the cutaneous nerves, are of central origin. But the question arises whether this effect of the poison is a direct one, or indirectly caused by the changes in the capacity of the vessels. It is known that convulsions may arise from arterial cerebral and spinal anaemia, as well as from excessive hyperae- mia, and more readily so from the former. The disturbances in the organs of sight and hearing are easily accounted for by the anaemia, and, indeed, a series of cases have been recently pub- lished of acute amaurosis after acute hemorrhage; now the accumulation of blood in the venous network which we have mentioned in acute ergot-poisoning, is closely analogous to acute 910 VON BOECK.—VEGETABLE POISONS. hemorrhage. But although we are led to assign a considerable share in the production of the series of symptoms to constriction of the arteries, it is impossible to exclude a direct influence of the poison upon the nervous system. In Zweifel1 s late work, as we have already mentioned, stress is laid upon the latter mode of action, and the symptoms of "Kriebelkrankheit" are to be traced to an initial excitement and subsequent paralysis of the central nervous system. Therefore, we refer the reader to the analysis of symptoms given under acute ergotism. There is no doubt that some of the symptoms depend upon the drain of fluid, caused by the repeated vomiting and diarrhoea. But the general symptoms are chiefly the result of the direct action of the poison on the mucous membrane of the stomach and intestine. The vomiting in the later stages of the illness may be regarded as central, and the later diarrhoea is traceable to the altered con- dition of the blood found in the intestine. Results of Autopsies. Frequent as deaths from spasmodic ergotism were in former times, very few good reports of the results of autopsies lie before us. The few physicians who have reported such autopsies are unanimous in stating that putrefaction sets in very rapidly. The heart is found bloodless and flaccid, the lungs in a condition of venous hyperaemia ; venous injection of cerebral membranes is very marked. Strongly injected patches are often found in the stomach and intestine, sometimes hemorrhagic and even gangre- nous erosions are met with. Evidences of venous hypersemia are found in the abdominal glands, in the liver, and the spleen, which are somewhat swollen and dark colored. Diagnosis and Differential Diagnosis. The diagnosis of chronic spasmodic ergot-poisoning is gener- ally not very difficult, especially as it usually partakes of the character of an epidemic, though of limited extent, and the his- tory is easily obtained. The disease, as such, may be confounded with spinal meningitis, or even with cerebro-spinal meningitis. ERGOT. 911 But the existence of convulsion of the flexors supplies an essential point of distinction. The absence of fever and the con- dition of the circulation may also assist in the diagnosis. It is distinguished from strychnine-poisoning by the essential differ- ence between the convulsions in the two cases; strychnine con- vulsions are constantly reflex convulsions, which is not the case in '' Kriebelkrankheit.'' Prognosis. The prognosis in chronic ergotism is different at different times, since the quantity of ergot contained in the wheat of dif- ferent years varies. Practically, the prognosis depends not only upon the quantity of poison introduced, but upon the individual constitution. Weakly persons, old people, and children suc- cumb more easily to ergotism than young and strong individuals. The prognosis depends considerably upon the time at which the poisoning is recognized, as an early recognition enables us to guard against the further introduction of the noxious substance. In other respects the prognosis is favorable if the convulsions come on at long intervals, if they remain confined to the extremi- ties, if the nutrition of the patient is comparatively unimpaired, if the diarrhoea and vomiting are slight, and if the changes in the circulation are inconsiderable; it is unfavorable if all these symp- toms are of an aggravated type. Mobility of the pupils, and a moist, warm skin are favorable signs. Treatment. The most important thing is to prevent the disease, which is comparatively easy, as its cause is so accurately known. The rare appearance of this disease in recent times is traceable to a more thorough purification of wheat from ergot, and to the im- portation of corn from other places into districts in which the crop has failed. Another reason is that, in modern times, people are accustomed to much more variety in their food, and are not limited to one kind as formerly; the introduction of potatoes has no doubt effected an improvement in this respect. Still it may 912 VON BOECK.—VEGETABLE POISONS. be well to make the danger of ergot a subject of school-instruc- tion, and to spread this knowledge among the general public at harvest-time in damp years. In practice, the first object must be to prevent further introduction of poison, and to replace the tainted bread by healthy food; the second will be to eliminate any poisoned bread still remaining in the gastro-intestinal region by emetics and purgatives. Drastic remedies are, however, to be avoided, as they may promote the continuance of diarrhoea. Remedies containing carbonic acid are advisable for the excessive vomiting, and moderate doses of opium for the diarrhoea. Car- diac contraction demands close attention, and must ultimately be treated with the usual stimulants. The cramps in the extremi- ties are relieved by friction of the skin, and patients also request that their convulsively contracted limbs be extended. Warm baths are also calculated to suppress or shorten the spasms. It is unnecessary to add that particular symptoms may indicate other remedies. Changes which Ergot undergoes in the Organism, There is no doubt that the active constituent of ergot is ab- sorbed into the fluids of the body, and flows with the blood through all the organs. It is probable, but by no means proved, that the excretion of the poison takes place partly through the urine, partly through the intestinal canal; it is further probable that the poison is contained also in some of the secretions, e. g., in the saliva, which accounts for the salivation ; but this much is certain, that it does not enter into the secretion of the breast—the milk—for all authors are agreed that sucklings are not affected, even when their mothers are suffering from ergotism; also in most cases the secretion of milk is not altogether suppressed. Whether a part of the poison introduced is decomposed within the body is not known. (See the same heading under Acute Ergot-Poisoning.) ERGOT. 913 Tests of Chronic Ergot-Poisoning. The properties of the bread adulterated with ergot should be the first subject of investigation. Bread containing ergot has a peculiar odor, a dark violet color, a sweetish but not exactly unpleasant taste; the flour, which contains large quantities of ergot, has also the same peculiar taste and a darker color. Small particles can be microscopically detected as belonging to ergot. When flour containing ergot is heated with caustic potash, a very characteristic odor, like herrings or old soap, arises; this odor lasts a long time, even when only one-seventy-second of ergot is mixed with the flour (Wittstein). Other tests recommended are less constant and not characteristic. We find some cases reported of illnesses resulting from ergot which, besides the symptoms of spasmodic ergotism, show also symptoms of gangrene in peripheral parts, such as the toes, fingers, etc. These cases form the transition from the spasmo- dic form of ergotism to the gangrenous, and thus prove that these two forms of disease are really dependent on the same cause, and that both may be regarded in a certain degree as different stages of one and the same disease, stages which, how- ever, have attained a certain substantive form, and by no means necessarily pass into one another, or follow as sequelse to each other. It is not certainly known why in the one case the ergot- ism assumes the spasmodic, in the other the gangrenous form. But it appears remarkable that the spasmodic form formerly prevailed chiefly in Germany, while the gangrenous form was found principally in France, and there particularly in the So- logne. But this difference does not hold universally, for epi- demics of the gangrenous form have appeared also in Germany, Austria, Russia, and Sweden. It is not known, whether this variety depends upon a difference in the activity of the ergot in different seasons, or whether such changes are the result of some peculiar property of the ground in which the corn grows. In VOL. XVIL— 58 914 VON BOECK.—VEGETABLE POISONS. the Sologne it was generally the ergot of maize which produced the poisonous symptoms, whereas in Germany the ergot of rye was almost exclusively mentioned as the cause of the disease. It is however, very improbable that the difference between these illnesses is dependent on the different parent plants, because, at least therapeutically, the same effects can be produced by the ergot of maize as by that of rye, when the quantities are equal.1 It is most probable, then, that there is a simple quantitative dif- ference in the absolute and relative quantity of the poison taken into the system. Gangrenous Ergotism. Gangrenous ergotism often raged formidably in vast epidem- ics in former ages. France and Switzerland were the countries most visited by this disease. Thus Falck mentions thirteen epi- demics, from the year 1630 till the year 1820, which were almost all confined to the countries above named, only few cases com- paratively occurring in Germany. This form of ergot-poisoning has become much more rare in modern times, and when it does occur it attacks only limited districts, generally only a few fami- lies. This diminution is traceable to accurate knowledge of the etiology of the disease, to increased freedom of communication, to the prevalence of mixed diet, etc. Still, that our age is not quite free from gangrenous ergotism is proved by the recurrence of different epidemics in the last thirty years. Bonjean" de- scribes one which, in 1844, attacked a family of eight persons in Savoy, and was caused by their partaking of flour which con- tained about twenty per cent, of ergot. Barrier3 mentions a not very severe outbreak of gangrenous ergotism in the departments of Isere, Loire, Haute Loire, Ardeche, and Rhone; an unfor- tunate maize harvest was the cause of this epidemic, about thirty 1 Jobert, Quelques observations sur les proprietees therapeutiques de l'Ergot de Ole. Gaz. des HGpit. No. 37. 1855. 2 Ergotisme gangraineux developpe chez deux enfants mules par l'usage d'un pain, qui contenait da seigle ergote. Compt. rend, de l'Acad. T. XIX. 3 De l'epidemie d'ergotisme gangreneux observee a l'Hotel de Dieu de Lyon en 1854 et 55. Gaz. med de Lyon. No. 10. 1855. ERGOT. 915 cases of which came under the notice of Barrier. Dr. Helm' reports a slight epidemic which broke out among the workmen on the railroad at Brunn, in Moravia, during the months of November and December. Etiology. The cause of gangrenous ergotism, as we have said, is doubt- less to be found in the ergot which is consumed with flour and bread. All that has been said about spasmodic ergotism applies here, so that we need only refer to that section. As has also been said, gangrenous ergotism is most probably only a quantita- tive aggravation of spasmodic ergotism, i. e., poisoning produced by large quantities of the ergot. Symptoms and Course of Gangrenous Ergotism. In the beginning of the illness we find the same symptoms as in spasmodic ergotism; the first symptom being violent cuta- neous irritation, formication, and modification of sensibility in the peripheral nerves. Identical symptoms also appear in con- nection with the stomach and intestinal canal—retching, nausea, vomiting, and diarrhoea ; the symptoms connected with the cen- tral nervous system are also the same—headache, and giddiness ; occasional contractions of the flexor muscles are also observed ; the changes in the cardiac contraction and in the fulness of the arteries, the disturbances in the activity of the organs of the senses are identical with those of spasmodic ergotism. This con- dition may last a longer or a shorter time, so that the epidemics may be distinguished as malignant or mild. The symptoms which characterize gangrenous ergotism as such often appear within from two to seven days, but are frequently delayed for two and three weeks. An erysipelatous redness shows itself on some spots in the periphery, most frequently on the toes and feet, but also on the fingers and hands, more rarely on the ears 1 Ueber Ergotismus gangrenosum Wochenblatt der k. k. Gesellschaft der Aerzte zn Wien. No. 11. 1856. 916 VON BOECK.—VEGETABLE POISONS. and the nose ; soon after the epidermis is raised like a bladder by serous exudation; the ichorous contents of this are soon dis- charged, and a gangrenous spot more or less large is left. Then dry gangrene develops very rapidly at the affected spot. The part affected is very painful while the redness is invading it, but later on it becomes quite insensible. On account of the eiysipelatous redness the disease was called Ignis sacer in former ages. The gangrenous spot may exhibit either the dry or moist form, according to whether the discharge was checked or encour- aged ; upon this also depends the greater or less in tenseness of the odor of putrefaction. In some cases the gangrene was lim- ited to one or more toes, sometimes only to single phalanges ; in other cases, however, the entire foot or hand was affected; not infrequently the gangrene extended to the trunk ; it was possi- ble for the patient to lose both feet or both arms. Indeed, a few cases are reported in which all four extremities were lost. The gangrenous parts become separated from the healthy tissue by a well-defined line of demarcation, and the affected part may either fall off of itself, or must be removed by an operation. This pro- cess of demarcation is often attended with serious disturbances of the general condition of the patient; sometimes a modified form of continued fever is developed, followed by phthisical changes ; in a few cases, from absorption of ichorous matter, pyaemia and septhsemia set in, and are, of course, fatal. When the gangrene was confined to parts of minor importance, the patients usually recovered ; greater losses were naturally more frequently fatal. In some cases obstinate diarrhoea brought on marasmus and death, even when the extent of the gangrene was not very considerable. We must mention, however, that in many cases the diseased process did not advance beyond the erysipe- latous redness; marked cyanosis may be observed, and yet a separation may take place, and the circulation be restored. The duration of the entire illness is very variable, and may be pro- tracted through several months. In favorable cases the course is ended in a few weeks. ERGOT. 917 Analysis of Symptoms—Nature of Gangrenous Ergotism. For the elucidation of most of the symptoms which have been mentioned, it is sufficient to refer to what has been already said of spasmodic ergotism. The gangrene is the only new symptom in gangrenous ergotism. This form of gangrene, like all other forms, depends on the fact that the part affected is deprived of its blood-supply, and its nutrition thereby arrested; conse- quently it must pass into a state of decomposition. The only question which can be advanced here is, whether it is inflamma- tion which leads to gangrene, or whether the process is of a non- inflammatory character, resembling that which occurs when all the vessels going to a limb are ligatured. When we consider that the initial so-called erysipelatous redness is simply depen- dent on the cyanosis, and that these spots are not, as in a case of inflammation, hot and swollen, but, on the contrary, they become very cold, and warmth cannot be restored in them, and that the affected limb is not at all swollen, the hypothesis that such a gangrene is of an inflammatory character must a priori be re- jected. When we further reflect that there is no fever at the out- set, the second hypothesis becomes still more probable. Such simple exclusion of an extremity from its ordinary blood-sup- ply is quite conceivable from our current views of the action of ergot on the vessels and the distribution of blood. The contraction of the small vessels, especially of the arteries, by ergot, particularly when the vis a tergo, i. e., the cardiac con- traction, is in a remarkable degree simultaneously affected by this poison, may lead to a complete emptying of blood not only in the separate smaller vessels, but also in the larger vascular trunks; and it is conceivable that by the failure of the blood- supply the arteries themselves (e. g., in the intima) may become diseased, so that thrombi readily form in them, and so the whole process may be characterized as thrombotic. This thrombotic process is likely to occur in those cases of slow progress in which gangrene does not set in till very late. The throwing off of the gangrenous limbs, the suppurative fever, the pysemia'and hectic are in accordance with general pathologi- 918 VON BOECK.--VEGETABLE POISONS. cal knowledge. If we ascribe the lion's share in the total effect of the poison to the action of ergot on the nervous centres, and regard the contraction of the vessels as a secondary influ- ence, as Zweifel does, the gangrene is certainly not very easy of explanation. Zweifel lays stress on the fact that gangrene from bed-sores arises very readily in parts which from any cause have lost their sensibility, and he is disposed to regard the gangrene in chronic ergotism as a kind of decubital gangrene, especially when it attacks chiefly the lower extremities, as these have to support, for the most part, the pressure of the whole body. This view, which has much to recommend it, does not, however, explain those cases in which gangrene attacked the upper ex- tremities, the nose, and the ears. Results of Autopsies. Very few autopsies have been performed on persons who have died of gangrenous ergotism, although material was not wanting, at least in former centuries. The reports that we possess contain nothing that is characteristic of this poison ; that the gangrenous parts have been found in different stages of mortification, and that inflammatory action existed around them, was to be ex- pected. The most striking fact is that mentioned by Bonjean, who states that he found the arteries leading to the gangrenous limbs in a healthy condition ; Barrier, on the contrary, maintains that he found a primary disease of the arteries ; he, however, stands alone in this statement. Diagnosis and Differential Diagnosis. The recognition of this disease is not difficult, if the mode of development of the gangrene is observed, and if the history and the etiological conditions are taken into consideration. The hypothesis of inflammatory gangrene will thus be excluded a priori. The only disease for which it might be mistaken is senile gangrene, for this may arise, especially if the arteries are affected, without inflammatory and feverish symptoms. The ERGOT. 919 condition of the heart, the full or empty state of the arteries and veins, and the circumstance that gangrenous ergotism attacks individuals of all ages, and generally several simultaneously, will enable us to distinguish between them. The season of the year will also greatly assist in the diagnosis. Prognosis. The prognosis rests chiefly upon the quantity of poison taken, and upon its activity, which, as has been stated above, differs according to the time and manner of consumption, the prepara- tion of the bread, etc. When gangrene has once broken out, the prognosis will mainly depend upon its extent. The condition of the patient as to nourishment, the possibility of keeping up his strength, the state of cardiac action, will naturally have an im- portant bearing on the prognosis. It may be stated in general that gangrenous ergotism is a very dangerous disease ; there have been epidemics in which sixty per cent, and more died. Of the epidemics which have occurred in modern times the mortality never exceeded ten per cent. It is needless to say that the patients, when they escape with life, have lost one or other limb. Treatment. In the outset of the case emetics and purgatives must be ad- ministered, to eliminate any poison remaining in the intestinal canal; the second measure of importance will be to avoid the use of ergot by introducing a suitable diet; no bread ought, therefore, to be allowed, but milk, meat, etc. In the further management of the case it will be advisable to increase the blood-pressure by stimulants, so as, if possible, to avert arterial anamiia in the peripheral parts, before gangrene appears. When the erysipelatous redness is seen on any spot, the supply of blood should be promoted by hot fomentations and warm bathing lo- cally, in order, if possible, to ward off venous hypersemia and stasis. After gangrene has set in, a strengthening regime may 920 VON BOECK.—VEGETABLE POISONS. prevent its spreading, and at the same time hasten the throwing off of the gangrenous parts. As dry gangrene is generally to be preferred to moist, it may be advisable to remove the epidermis from the gangrenous parts ; this leads to drying up, and at any rate diminishes the formation and absorption of ichor. The re- moval of the mortified parts after the formation of a line of de- marcation is the business of the surgeon. The anaesthesia, neu- ralgia, paralytic symptoms, etc., which sometimes remain behind, are to be treated as substantive diseases. The use of tannin—recommended by Griepenkerl as a chemical antidote—can, naturally, be of use only so long as the poisonous bread, etc., remains in the stomach. Certainly no combination between tannin and ergotine can take place in the blood. No- body, in these days, will venture to suggest the venesection which was so freely adopted formerly. The use of narcotics deserves the greatest attention in all stages of the disease. The nature of the symptoms must guide our decision whether opium, morphine, chloral, or other nar- cotics should be administered in the special case. For the testing of the poison in bread, flour, etc., and the changes which ergot undergoes in the organism, we refer the reader to what has been said in the previous section. Poisoning by Poisonous Fungi. The study of poisonous fungi is one of the most difficult in toxicology; and it is so because not only is our acquaintance with the different varieties and species of these fungi very limited, but also because we know little or nothing about the active poi- sonous principles contained in them. Some authors pronounce almost all fungi to be poisonous, whilst others say that very few are so. This difference of opinion arises from the fact that some con- sider certain fungi to be poisonous because they may have pro- duced symptoms of poisoning in those who have partaken of them, and they do not consider whether it is that these funo-i EDIBLE FUNGI.—MUSHROOMS. 921 contain an integral poisonous constituent, or whether other cir- cumstances have tended to make the eating of them injurious. If we assert that a fungus is poisonous, we must be able to prove that it, taken as a plant, contains a substance which, under or- dinary circumstances, acts poisonously on the life and functions of the human or animal organism. If a fungus does not produce poisonous effects under ordinary circumstances, but leads to symptoms of illness when special conditions prevail, the fun- gus, as such, is not to be designated as poisonous. Now there certainly are fungi enough which may be eaten with perfect safety in an ordinary way, but which occasionally cause fatal illnesses. It is, therefore, important, in the first place, to become more intimately acquainted with these special circumstances. Many persons are attacked with sickness more or less violent from eat- ing perfectly unsuspected mushrooms, while others can eat an equal quantity of these same mushrooms, prepared in the same way, and not suffer in the least. This difference is traceable to individual peculiarities, to a sort of idiosyncrasy. A further fact is that mushrooms are very apt to create indi- gestions and gastric and intestinal catarrh, so that the consump- tion of large quantities of absolutely harmless mushrooms may lead to these complaints with some severe symptoms, which may be taken for symptoms of poisoning. Again, mushrooms are very watery substances ; they contain up to 90 per cent, of water, but they are also comparatively rich in vegetable albumen, so that they contain between 3.2 and 7.2 per cent, of nitrogen (Schlossberger and Doepping). Substances so composed become very easily decomposed, and the products of this decomposition may, as in the case of meat, cheese, sau- sages, and other kinds of food, act very injuriously on the organ- ism, especially the alimentary canal, and may, under certain circumstances, even produce fatal effects. But these occurrences do not furnish us with data for concluding that the mushrooms are in themselves poisonous. It would appear, from many cases on record, that the process of decomposition may be furthered by the place in which mush- rooms are found, their age, the conditions of weather, by their 922 VON BOECK.—VEGETABLE POISONS. being left a long time after gathering, and many similar circum- stances, so that mushrooms, in themselves, may come to act inju- riously. It must be left an open question whether the method of cookin^mushrooms has any influence in this direction, or whether they can, by culinary art, be made more or less digestible in the stomach. A few examples may be quoted from reports of cases in eluci- dation of our theory. The Morchella (morel) and Helvella esculenta are rightly re- garded as eatable fungi and much esteemed by gourmands, and yet they have very often produced symptoms of poisoning. Thus Dr. Keber' relates the history of the poisoning of six persons, who, after partaking of these fungi, were attacked with vomiting and diarrhoea which lasted for sixty hours. As sequela of the acute gastro-intestinal affection, they all showed symptoms of icterus catarrhalis. In their case it was expressly stated that the morels had been gathered in very damp weather and not thoroughly cleansed. Dr. Schubert2 reports the poisoning of two children of eight and four years of age respectively, after eating morels. The children were taken ill about six hours after with vomiting and pain in the bowels, and died in convulsions and sopor twenty-one and forty-five hours respectively after the intro- duction of the fungi, while none of the other members of the family suffered—a proof that children succumb more readily to the action of fungi than adults. The Morchella and Helvella contain a good deal of albumen and fat. O. Kohlrausch'3 found in the dried Morchella esculenta 35 per cent, of protein and 2.39 per cent, of fat; in Morchella conica 2.96 per cent, of protein and 2.4 per cent, of fat; in Helvella esculenta 26.6 per cent, of protein and 2.2 per cent, of fat. On the other hand, common mushrooms contain only 17.0 of albumen and 1.4 per cent, of fat. Accordingly poisonings by mushrooms 1 Vergiftungszufiille nach dem Genusse der Helvella esculenta. Preussische Vereins- zeitung. No. 32. 1846. 8 Aeussern die Morcheln zuweilen giftige Eigenschaften ? Casper's Wochenschrift. Dec. 1844. 3 Ueber die Zusammensetzung einiger essbaren Pilze mit besonderer Beriicksichti- gung ihrea Nahrungswerthes. Gottingen. 1887. Dissertation. EDIBLE FUNGI.—MUSHROOMS. 923 (Agaricus campestris) are much more rare, although they do oc- cur after decayed mushrooms have been eaten. Slighter poisonings, characterized by vomiting, diarrhoea, and slight collapse are reported as the result of almost ail edible fungi. The warming-up a second time of dishes containing mush- rooms very frequently leads to illnesses, as is proved by many cases on record. As regards fungi which are constantly poisonous under ordi- nary conditions, and which must therefore be regarded as actu- ally poisonous fungi, we may with confidence accept the classifi- cation of Th. Husemann,1 who specifies as actually poisonous fungi only Amanita muscaria, Amanita phalloides, Russula inte- gra, Boletus luridus, and their varieties. To these belong Agari- cus integer, foetens, bulbosus, rimosus, fastibilis, crustuliniformis, and a few others. These fungi are poisonous : i. e., they contain as integral constituent a substance which acts destructively upon animal life—a poisonous substance. Disease through Decayed Fungi Symptoms and Course. It is characteristic of all diseases caused by the fungi usually eaten that they produce violent gastro-intestinal symptoms. As a rule, the symptoms appear after six or eight hours, seldom earlier, frequently later, so that, in some cases, the first symp- toms of illness do not set in till after eighteen to twenty-four hours. They usually begin with pains in the stomach and intes- tine ; violent colic is the earliest symptom, soon followed by great nausea, with increase of salivary secretion, and then vomit- ing. This vomiting is seldom over at once ; it is generally re- peated at longer or shorter intervals, and may last three days and even longer. Soon after the vomiting begins diarrhoea set* 1 Ueber die medicinische Bedeutung der Pilze mit vorzugsweiser Beruchsichtigung ihrer toxischen und diiitetischen Eigenschaften. Schuchardt's Zeitschrift f. pract Medi- cin. 1865. III. Heft. p. 221 ff; and Husemann's Toxikologie. 1862. p. 881. 924 VON BOECK.—VEGETABLE POISONS. in, and it may also last a long time. At first the vomited matters as well as the fseces contain the remains of the fungi consumed. These are only recognizable for a short time in the vomited mat- ters, as the stomach soon gets wholly rid of its contents. But the rudera of the fungi are generally found in the fseces even on the second and third day ; therefore they remain a comparatively long time in the intestinal canal. But even when the last traces of the mushrooms have been eliminated by the evacuations, this simple removal of the noxious substance by no means puts an end to the vomiting and purging, but purely serous evacuations, more or less profuse, follow, very like the rice-water stools which are characteristic of European and Asiatic cholera. The gastro- intestinal symptoms are directly followed by those of acute drain of fluid. The plumpness of the skin disappears, the eyes sink back in their orbits, the features become pinched and cold, slight cyanosis spreads over the whole body, cardiac contraction be- comes insufficient, respiration is labored, and convulsions appear in different groups of muscles, while the patient suffers from insatiable thirst. In some cases these symptoms are succeeded by a condition of sopor, and sometimes, with children, by gen- eral convulsions. These latter symptoms have given rise to the belief that an actual poison is developed in decayed mushrooms, which acts toxically on the cerebro-spinal nervous system. We incline, however, to the view that the acute drain of fluid and the disturbance of circulation inseparable from it, together with the imperfect decarbonization of the blood, produce this state of sopor, and may also cause the convulsions, especially in chil- dren, whose reflex inhibitory apparatus is decidedly less ener- getic in its action than that of adults, so that it is quite unneces- sary to assume the existence of a poisonous substance which has not been detected. It is self-evident that this choleraic condition may kill chil dren and weak and elderly people. In such fatal cases collapse advances gradually, carbonic acid poisoning gains ground more and more, and so the scene may close in an algid stage, even after the illness has lasted five or six days. As a rule, however, these cases end in recovery, either because the acute drain of fluid does not reach so alarming a height, or because the physical EDIBLE FUNGI.—MUSHROOMS. 926 constitution overcomes that and its consequences. Convales- cence is generally tolerably rapid, and recovery complete. Only in some rare cases it is a long time before recovery sets in. Results of Autopsies. Such reports of autopsies as we possess yield no characteris- tic results. The signs of acute gastric and intestinal catarrh, and the evidences of inspissation of the blood and of death brought on by cardiac paralysis are the only more or less con- stant phenomena. In some cases, especially when death super-' venes soon, remains of the fungi may be found in the intestinal canal, which may determine the diagnosis. Diagnosis and Differential Diagnosis. The recognition of the illness described as arising from mush- rooms depends chiefly on the history and then on the inspection of the evacuations. If these criteria fail, it is often impossible to differentiate from other diseases—cholera, acute gastric and intestinal catarrh—and only a chemical examination can prevent its being mistaken for arsenic-poisoning. The question whether it is caused by poisonous fungi can only be answered by exam- ination of the mushrooms which have been eaten. As to the rest, the more purely the disturbances are gastro-intestinal, and the fewer the other symptoms, the safer the diagnosis that only simple, and not poisonous, mushrooms are the cause of the illness. Treatment. The treatment of this illness brought on by decayed mush- rooms consists naturally in procuring the discharge from the stomach and intestines of the injurious substances which have been introduced, as quickly and completely as possible. All kinds of emetics and purgatives may be used for this purpose ; yet oleaginous aperients are preferable to saline in case any really poisonous fungi should perchance have been eaten. The 926 VON BOECK.—VEGETABLE POISONS. attention of the physician will naturally be directed to the con- sequences of acute drain of fluid, disturbances in circulation and respiration. He will try to avert collapse by administering stimulants in all possible forms—alcohol, ether, camphor, etc.; he will strive to overcome the subjective and objective dyspnoea by stimulating the skin, to resist the tendency to over-chilling of the body by the application of heat, to relieve the intolerable thirst by internal administration of ice, and by the use of opiates to moderate the subjective sufferings of the patient, and to di- minish the hypercatharsis. With regard to poisoning by actually toxic fungi, intoxica- tion with the fly-fungus (Amanita muscaria) is of most interest to us. Poisoning with Amanita Muscaria. Fly-Fungus—Muscarine. It is not only the frequent recurrence of this kind of poison- ing which claims the attention of the practical physician, but the fact that we have learned to recognize the poisonous prin- ciple of the fly-fungus in muscarine, and we can follow experi- mentally its mode of action. Various investigators in former times had endeavored with imperfect success to isolate the poisonous agent in the fly-fungus and prepare it in a purer condition, but O. Schmiedeberg and R. Koppe' were the first to procure from Amanita muscaria an alka- loid which possesses distinctly poisonous properties and fully accounts for the action of fly-fungus-poisoning. O. Schmiede- berg and his pupils have so thoroughly studied this alkaloid, as well in its chemical as in its physiological properties, that mus- carine may be counted among our best-known poisons. Muscarine is a colorless syrupy mass without odor or taste, 1 Das Muscarin, das giftige Alkaloid des Fliegenpilzes, seine Darstellnng, chemischen Eigenschaften, physiologischen Wirkungen, toxikologische Bedeutung und sein Ver- haltniss zur Pilzvergiftung im Allgemeinen. Leipzig. 1869. F. C. W. Vogel. POISONOUS FUNGI.—MUSCARINE. 927 readily soluble in water and absolute alcohol, insoluble in ether and chloroform ; it forms salts with acids, as, e. g., with sulphu- ric acid a crystalline salt, which deliquesces when exposed to the air. In a free condition muscarine has a very strong alkaline reaction. The quantity of this alkaloid present in the fly-fun- gus is not exactly determined ; the preparation of it is very com- plicated, and the portion extracted forms about one-fifth per cent, of the dry fungus. Etiology. As poisoning by pure muscarine has never yet taken place in the human subject, but the fly-fungus is always the agent by which it is induced, a few words must be said about this fungus. An infusion or simple watery extract, as well as the juice or small particles of the fresh fungus, acts poisonously on flies, but when dried it loses this property. In addition to muscarine, which is innocuous to flies, this fungus contains another sub- stance, which is poisonous, at least to flies, and which is either destroyed or disappears when the fungus is dried.1 Another body is also found in this fungus, as Schmiedeberg and also Harnacka have shown, a body chemically related to muscarine, amanitine, which exercises no influence on animals. This amani- tine (Harnack) most probably passes directly into muscarine when combined with oxygen. In comparing the chemical compo- sition of these two bodies, we find simply one equivalent more of O in muscarine than in amanitine. The double chloride of gold and muscarine is, according to Harnack, =OsHMN02Cl + AuCl3; the same salt of amanitine = OsH14N0Cl-r-AuCl3. Harnack con- siders it probable that amanitine is identical with chlorine. The fiy-fungus acts poisonously upon human beings in proportion to the amount of muscarine it contains. 1 Perhaps the substance which is poisonous to flies is that fugitive body which Born- traeger and Kussmaal obtained by distilling the fly-fungus, and which was like a fatty acid° and when one drop was given to a rabbit killed it, although rabbits steadily resist the action of muscarine. Verhand. d. natur. med. Vereins zu Heidelberg. I. p. 18. 1857. 2 Untersuchungen uber Fliegenpilz-Alkaloide. Arch, fur experimenteUe Pathologie und Pharmacologic IV Bel 3. Hft. p. 168 ff. 1875. 928 VON BOECK.—VEGETABLE POISONS. The common cause of muscarine-poisoning is eating the fly- fungus, either from its being mistaken for edible fungi, especi- ally for Amanita csesarea (the so-called golden agaric), or from ignorance of its poisonous qualities. The fly-fungus appears in our woods between August and October ; its cap (pileus) is red, reddish yellow, or yellowish, and bears white scaly warts; its edge is furrowed with white; the flesh is white, and under the outer skin is surrounded by a reddish-yellow rim ; the stem is knotty or hollow with a loose white ring ; below it is smooth, and close to the ground knobby with an excrescent scaly rind. The lamellae are white or yellow (Husemann). Poisoning by means of this fungus was more common for- merly than now, an advance which depends on the general spread of the knowledge of its poisonous properties ; yet there are very recent reports of this kind of poisoning. Thus, Wutscher' re- ports the poisoning of a man of sixty, and a woman forty years of age; the latter, half an hour after partaking of cooked fly- fungus was attacked with symptoms of gastro-enteritis, twitch- ings, extensor cramps, and disturbances of vision ; in the case of the man, the symptoms were less rapidly developed, and con- sisted chiefly of excitement and disturbance of the sensorium. Both recovered. Two cases reported by Cosserat,2 also termi- nated in recovery. In the year 1859 five French officers at Corte, in Corsica, died from eating a dish of this fungus. Pathology. Symptoms and Course. The symptoms of poisoning appear very soon after the fungi have been eaten ; usually not later than half an hour to an hour. But sometimes a longer period of twelve hours and even more elapses before actual symptoms of poisoning appear. These dif- ferences as to time depend less on individual peculiarities than on the greater or less quantity of the fungi consumed, and the 1 Wiener med. Presse. 17. 1872. a Union med. 131. p. 714. 1873. POISONOUS FUNGI.—MUSCARINE. 929 rapidity or otherwise of absorption, which, as is well known, may be promoted or hindered by a number of factors. Yiolent gastric symptoms are scarcely ever quite absent in a case of poi- soning with Amanita muscaria, although the colicky pains, and especially the vomiting and diarrhoea, seldom reach such a height as in cases of the introduction of decayed edible mushrooms. There are even numerous cases on record, in which the gastric and intestinal symptoms have been only secondary, while dis- turbances of the central nervous system formed the more promi- nent main features. The action of this poison generally sets in with more or less violent colic, accompanied with vomiting and subsequent diar- rhoea. The excreta contain remains of the fungi which have been eaten. To these symptoms are added cerebral disturbances ; the patients think they are drunk, become violently excited; thus, e. g., a girl who had eaten some of these fungi ran about the house in her shift, knocked her head against the wall, and screamed like a person possessed (Cosserat); others suffer from disturbed vision ; they see everything dimly, as if wrapt in a mist; things float before their eyes; attacks 01 an epileptic nature and actual trismus have been observed. Then a state of sopor gradually sets in, in which the excitability of the sensory and reflex nerves is more or less lowered or quite destroyed. The pulse is, as a rule, retarded, the arteries are constricted, the pulse becomes thread-like, the respiration is generally short and stertorous, the pupils are dilated, the extremities and the fea- tures are cold, and death may supervene from progressive loss of cardiac power. If the case takes a favorable turn the patient awakes again out of the state of sopor, his pulse becomes quicker and stronger, his respiration freer, and in a longer or shorter time complete recovery sets in. The more rapid the awakening out of sopor, the more rapid the restoration to health. In slighter cases and with judicious treatment sopor may be recovered from, even after it has lasted from six to eight hours. The period of duration of the whole course of muscarine-poisoning is very dif- ferent ; it is especially dependent on the quantity of poison introduced, on absorption, the occurrence of vomiting, etc, Death may supervene in a few hours (six to twelve) after the VOL. XVII.—59 930 VON BOECK.—VEGETABLE POISONS. eating of the poisonous fungi, but usually the course is more protracted, so that the fatal result occurs towards the end of the second or third day. The cases which terminate in recovery are almost always of longer duration. It is impossible to state pre- cisely the quantity of fly-fungus which is sufficient to produce poisoning, but it is certain that even small portions may give rise to violent symptoms. Of pure muscarine, according to Schmiede- berg and Koppe, from an eighth to a fifth of a grain (eight to twelve milligrammes) are sufficient to destroy life in a cat in eighteen to fifteen minutes, and from one-twenty-second to one- sixteenth of a grain (three to four milligrammes) to kill it in two to twelve hours. One-thirteenth of a grain (five milligrammes) of muscarine produces in the human subject myosis, loss of focalizing power, abundant secretion of saliva, determination of blood to the head, flushed face, perspiration over the whole body, giddiness, anxiety, griping and rumbling in the bowels, and weight in the head (Schmiedeberg). Analysis of Symptoms—Nature of Muscarine-Poisoning. The symptoms produced by muscarine in animals entirely correspond to those which poisonous fungi produce in the hu- man subject. In cats we observe increased salivary secretion, vomiting, diarrhoea, rumbling in the bowels, wabbling, staggering gait, contraction of the pupils, frequency of respiration, dysp- noea. The vomiting and diarrhoea subside, respiration becomes less frequent, convulsions set in, respiration ceases, death super- venes. It appears, then, that the gastro-enteritic symptoms also are dependent on muscarine alone, and not on other substances mixed with it. The intestine, under the influence of muscarine, becomes subject to tetanic contractions, to which the diarrhoea, constipation, abdominal pains, etc., are traceable. We are unable to account for this effect on the intestinal muscles, or for the symptoms produced upon the brain. It is the influence of muscarine upon the brain which induces the inhabitants of Eastern Asia, e. g., the Samoiedes, Ostiaks, POISONOUS FUNGI.—MUSCARINE. 931 Koraks,1 and Kamtschadales, to buy these fungi, even at a high price, and consume them. They become at first very cheerful and merry, and subsequently fall into a kind of sopor, from which they awake in a state of exhaustion. The passion of these races for this species of intoxication is so great that the poorer people drink the urine of the rich who have eaten these fungi in order to procure this intoxication. This custom leads us to conclude that muscarine passes unchanged through the blood and the organism, and is excreted unchanged in the urine. It appears, from what has been said, that muscarine must first throw the brain into a state of increased excitability and after- wards into a condition of reduced excitability ; it is even highly probable that muscarine first excites and subsequently paralyzes the brain-cells. In this respect muscarine is closely allied to opium, hashish, alcohol, etc. The influence of muscarine on the heart and its contractions is very remarkable. The motor ganglia in the heart are at first excited, so that at the onset of the case in the human sub- ject we often find increased frequency of pulse. The principal action of muscarine, however, is exercised upon the inhibitory organs. When we inject T|7 of a grain (half a milligramme) subcutaneously into a frog, or bring a solution of muscarine into direct contact with the heart, the heart is almost imme- diately arrested in diastole. But if, during this suspension of cardiac action induced by muscarine, we irritate the heart in any way, it contracts—a proof that the cause of the cessa- tion does not lie in the cardiac muscle. Section of the vagi has no effect upon this inaction of the heart caused by musca- rine ; therefore those inhibitory organs residing in the heart itself are placed in a condition of great excitement by musca- rine, and this excitement is powerful enough to paralyze all the contractile power of the heart. It is these same inhibitory organs which are paralyzed by atropine. This influence of muscarine upon the inhibitory organs in the heart must produce an initial retardation of the heart-stroke, 1 Kenan, Auszug im Jahresberichte iiber Pharmacognosie, etc. von Wiggei Husemann. 1872. pp. 534-535. 932 VOX BOECK.—VEGETABLE POISONS. succeeded by absolute cessation, especially when large quantities of muscarine have been conveyed into the blood. In the early stage of the action of muscarine respiration is more frequent and labored than in the natural condition; later on there is a steady diminution of the frequency of respiratory movements, till at last they cease altogether. These symptoms in the respiratory apparatus proceed from an initial excitement and subsequent paralysis of the central organ in the medulla oblongata which governs respiration. The blood-vessels are constricted for a short time in the out- set of muscarine action, and afterwards dilated, as Bogoss- lowsky ' has observed. This vascular dilatation, combined with the diminution of frequency of cardiac pulsations, causes a de- crease of blood-pressure, amounting sometimes to one-third of the total amount. The flow of saliva which attends muscarine-poisoning is the consequence of an exciting influence exercised by muscarine upon the peripheral extremities of the secretory nerves ; at least we are led to this conclusion by the circumstance that section of these secretory nerves does not affect the secretion of saliva. Prevost" states that he has directly observed in the dog an in- crease in the secretion of the pancreatic juice under the influence of muscarine. He also asserts that the secretion of urine and bile is promoted by muscarine. It would appear that these effects are only dependent on the change in the circulation, and it is certainly probable that these effects are only observable in the first stage of muscarine action, before blood-pressure has been reduced ; once it is reduced, an increase of the secretion of urine is scarcely conceivable. We must now return to the changes in power of vision. Krenchel3 has published a very good report of the changes of this kind produced by muscarine. Even small doses of musca- rine lead to disturbances in the accommodating power, which are 1 Centralblatt fur die med. Wissenschaften. 97. 1870. 2 Gaz. med. de Paris. 4. Ser. T. 3. p. 243 ; and Compt. rend. T. 49. p. 381. 3 Ueber die Wirkung des Muscarins auf Accommodation und Pupille. Arch, fiir Ophthalmologic Bd. 20. Abthl. 1. p. 135 ff. POISONOUS FUNGI.—MUSCARINE. 933 characterized as accommodation-convulsions. With somewhat larger doses a not very marked contraction of the pupils, myo- sis, sets in. This myosis depends on excitement of the sphincter iridis itself, or on that of the oculo-motor nerve which governs it. The hypothesis of paralysis of the dilatator pupillaB or of the sympathetic nerve connected with it is inadmissible. Most of the experimental facts quoted in this section are taken from the work of Schmiedeberg and Koppe, already mentioned; the re- port of Bogosslowsky also, who experimented with a very power- ful extract of fly-fungus, coincides with theirs in most points. Results of Autopsies. The results of autopsies performed upon persons who have died of poisoning from fungi are by no means characteristic. The signs of acute catarrh are more or less pronounced in the stomach and the intestinal canal; and in most cases remains of the fun- gus are to be found in the contents of the intestine. As for the rest, the evidences of death caused by cessation of cardiac action or by asphyxia are found. Maschka,1 who has performed a con- siderable number of autopsies of this kind, stated that in cases of poisoning by mushrooms especially, the absence of cadaveric rigidity is characteristic. This, however, is an error, for we learn from the experiments of Borntraeger and Kussmauls that cada- veric rigidity was developed very rapidly and with tolerable com- pleteness, but that (and this is very noteworthy) it also disappears rapidly ; in the case of rabbits, after four hours. It would appear, however, from the experiments of Maschka and Husemann * that fatty degeneration of various organs takes place under the in- 1 Einiges iiber die Vergiftung mit Schwammen. Prager Vierteljahrschrift. No. 29. 16. July. 1856. * Verhandlungen des naturhistorisch-medicinischen Vereins. zu Heidelberg. I. p. 18. 1857. 3 Die Pilze in oconomischer, technischer und toxicologischer Hinsicht. • A work crowned by the Imperial Academy with the Orfila prize, by E. Boudier. Translated and annotated by Th. Husemann, with two lithographic tables. 1867. p. 181. The title of E. Boudier's work is: Des champignons au point de vue de leurs caracteres nsuels, chimiques, et toxicologiques. Paris. 1808. 934 VON BOECK.—VEGETABLE POISONS. fluence of poisonous fungi in general, and of the fly-fungus in particular. For Maschka found, in dissecting several persons who had died in September, 1854, at Prague and in its suburbs from mushroom-poisoning (apparently Amanita phalloides seu venenosa), numerous ecchymoses on the pleura pulmonalis and costalis, varying from the size of a millet-seed to that of a thaler. He found similar ecchymoses in the liver, in the lungs, in the cardiac muscle, in the walls of the stomach, in the spleen, and in the kidneys. Husemann insists specially upon fatty degenera- tion of the liver in mushroom-poisoning. Maschka also found the urinary bladder distended with urine; sometimes it was found to reach to the navel. The blood is generally fluid and cherry- colored ; it is chiefly found collected in the larger veins. Diagnosis and Differential Diagnosis. The recognition of muscarine-poisoning, as such, depends chiefly on the inspection of the matters vomited and the faeces. As a rule, remains of fungi will be found in these. But should vomiting and diarrhoea be absent, as is quite possible, the history of the case will provide important data. The season of the year will also aid the diagnosis, for by far the greater number of cases of fly-fungus-poisoning occur in the mushroom season, i. e., in August, September, and October. As to the rest, one of the prominent symptoms of fly-fungus-poisoning is the marked re- tardation of respiration and of the pulse; but as these sjmiptoms attend the action of many other poisons, they cannot be regarded as characteristic. It will be quite possible to confound this poi- soning with that caused by other poisonous fungi, and this can only be prevented by finding characteristic botanic signs in the portions of fungi found in the vomited matters. It is also pos- sible to mistake the action of this poison for that of narcotics. But alcohol would be readily detected by its odor, opium and morphine by the contraction of the pupils ad maximum (in mus- carine-poisoning the contraction is less marked), atropine and hyoscyamine by the great dilation of the pupils. In most cases it will also be easy to exclude the possibility of cerebral disease, and, at any rate, even should paralytic symptoms, contractions, POISONOUS FUNGI.—MUSCARINE. 935 etc., be absent, the course of the illness and the examination of the fseces wHl facilitate diagnosis. Prognosis. Cases of poisoning by means of the fly-fungus are the most severe of all, and therefore the prognosis is always very dubious. Still a number of factors powerfully influence the final result. In the first place, the quantity of the fungus which has been taken is of great importance, for although small portions of this poison- ous fungus have produced fatal consequences, still it is self-evi- dent that the greater the quantity which has been introduced, the greater the danger. The period at which vomiting and diar- rhoea (if present) occur is very important for the prognosis; for the same reason, the speedy interference of medical treatment has great influence on the course and the result of the poisoning process. Practically, the greatest stress must be laid upon the state of cardiac contraction and of respiration. In general, final recovery is probable, if death has not supervened on the third day. If this danger be surmounted, we may look for a complete recovery, for, though the period of convalescence may be pro- tracted for weeks, no permanent ill effect of the poisoning re- mains behind. Treatment. When the physician finds that poisoning by fly-fungus is in question, he will naturally seek to further the elimination of the fungi from the system as rapidly as possible, and for this pur- pose emetics are of the first importance. Still, it must be remem- bered that in many cases their action is slow, if, indeed, they do not remain absolutely inert. Therefore, very energetic emetics must be employed: tartarized antimony with ipecacuanha in suffi- cient doses, or vomiting must be induced by tickling the throat and uvula. It is needless to say that the stomach-pump will be ineffectual in this form of poisoning. As we know by experience that these fungi may remain for several days in the intestinal canal, we must endeavor to eliminate them by purgatives. Castor 936 VON BOECK.—VEGETABLE POISONS. oil, with perhaps the addition of a drop of croton oil, will prove most effectual; oleaginous aperients are preferable to saline or watery ones, or to those charged with vegetable acids, because muscarine is very readily soluble in water, especially in acidu- lated water. Tannin may just be mentioned as at least partially a chemical antidote ; but we must not calculate too decidedly upon its suc- cess, as it does not throw down muscarine completely. Schmiedeberg pronounces atropine to be an antidote in the real sense of the word, and states that in many respects and in many of its effects it has a directly opposite influence to that of muscarine on particular organs, even though it cannot be proved that an actually double-sided antagonism exists between the two poisons. In order to place this question in the right light, it is necessary to confront the individual symptoms and effects of the two poisons with each other. Muscarine contracts the pupils, atropine dilates them. A pupil contracted by muscarine becomes dilated by atropine, but an atropinized eye is not contracted by muscarine. Muscarine promotes salivary secretion, which atropine has the power of checking ; whereas large doses of muscarine fail to remove the dryness which atropine creates in the palate and throat. Mus- carine, in the early stage of its action, produces dyspncea by stimulating the respiratory centre; this disappears under the influence of atropine. Again, the intestinal tetanus which mus- carine produces gives way upon the administration of atropine, or it fails to appear in animals which have been previously atro- pinized. With regard to the heart, the antagonism between the two poisons is very striking. Very small, even minimum doses of muscarine arrest the frog's heart in diastole; a very minute quantity of atropine restores the contraction ; and when the ani- mal is first atropinized and then treated with muscarine, the con- traction is not arrested at all. It appears, from the investigations of Schmiedeberg and Koppe, and from those of R. Boehm, that both poisons act, though in opposite senses, on the inhibitory apparatus in the heart, but that the paralyzing action of atropine is more powerful than the stimulating effect of muscarine. We conclude, then, that atropine may be very effectual as an anti- POISONOUS FUNGI.—MUSCARINE. 937 dote to muscarine-poisoning, whereas muscarine exercises no important influence against atropine-poisoning. It is proved by some experiments of Schmiedeberg and Koppe, that animals are but slightly affected by even fatal doses of muscarine, when they have been previously injected subcuta- neously with small quantities of atropine. In clinical treatment, therefore, we would earnestly recom- mend the administration of small doses of atropine ; larger doses must be avoided, lest they should produce atropine-poisoning. No experiments on the human subject have been as yet reported. For the rest, the treatment must be guided by the symptoms, and especially by the condition of the respiration and circula- tion. Cutaneous irritation and internal stimulants may be in- dicated. Changes which Muscarine undergoes in the Bodies of Animals.—Tests for Muscarine. Muscarine is very readily soluble in water; indeed, we have only to cut up the fungi, lay them in water acidulated with acetic acid, and press out the juice; this process frequently repeated will render the fungi completely innocuous, so that they may be eaten without danger. The liquid in which they have been expressed becomes of course poisonous through this process.1 This ready solubility of the poison sufficiently accounts for its rapid absorption; that the poison is not readily altered is proved by the circumstance that it is not decomposed by the boiling and drying of the fungi, and that it passes out of the sys- tem unchanged in the urine, as is proved by the report given above of the intoxicating effect of the urine of those who con- sume these fungi. Should it be necessary to test for muscarine-poisoning in « Pouchet fed dogs for months on these fungi, thus rendered innocuous, and they nourished upon them ; but dogs which had drunk the water in which the fungi had been expressed, all died in twenty-four to thirty six hours. Indeed, Gerard himself and his family partook of fungi thus treated, without the slightest ill consequence. Taylor's work on Poisons, published by Seydeler. Coin. 1863. III. Vol. p. 263. 938 VON BOECK.—VEGETABLE POISONS. criminal cases, in addition to the botanical test furnished by the remains of the fungi which may be found in the stomach and the intestinal canal, the so-called physiological test must be used as the most decisive. In many cases the common unchanged urine applied directly to the frog's heart will be sufficient to arrest it immediately in diastole ; but the effect will be more surely produced by concen- trated urine. Sometimes it may be desirable to make an extract of the re- mains of the fungi found in the stomach and intestinal canal, or in the vomited matters and the fseces, and with this extract to make the experiment on the frog's heart. It is easily shown that the cessation of cardiac contraction thus produced does not depend on paralysis, because the heart responds to mechanical or electrical irritation by several rhythmic contractions, and pul- sation may be restored by small doses of atropine. Poisoning by Amanita Phalloides s. Yenenosa. Agaricus Bulbosus s. Viridis. The cap (pileus) of this fungus is either quite white, or the white has a mixture of yellow or green ; the rim is white, unfur- rowed ; the lamella- are white; the stem is knobby low down; the flesh always white ; it is found during the whole summer in lightly wooded places. To its varieties belong Agaricus citrinus, virescens, and Hypophyllum albocitrinum (Husemann). Etiology. Cases of poisoning by these fungi are rather frequent and generally proceed from ignorance of their poisonous character or from mistaking them for edible mushrooms. Reports of such cases are numerous both in ancient and in modern times. Amanita bulbosa and its varieties produce some of the most dangerous of POISONOUS FUNGI.—AMANITA PHALLOIDES. 939 fungus poisonings. We have not yet succeeded in ascertaining accurately the active principle of this fungus, though great efforts have been made to discover it. Sicard and Schoras ' first expressed the opinion that the active constituents of poisonous fungi were bases ; then Letellier and Speneux * obtained an acrid, fixed poison, which acted violently on the stomach and the in- testinal canal, and also a second poison which they called amani- tin, and which affected the nerves. This amanitin was a brown- ish, non-crystalline, readily soluble substance, devoid of taste and odor ; when treated with acids, it became partially converted into sugar, like the glucosides. These two poisonous bodies could not be obtained pure, but consisted of a mixture of several substances. E. Boudier3 obtained an alkaline body out of Ama- nita bulbosa, which he called bulbosine ; it is distinguished from muscarine by a sharp, bitter taste, yet it strikingly resembles muscarine in its behavior as to solubility, so that Schmiedeberg considers bulbosine to be identical with muscarine. For Bou- dier's bulbosine is readily soluble in water and absolute alcohol, insoluble or very sparingly soluble in ether and chloroform, like muscarine. Still, notwithstanding the probability of Schmiede- berg's view, no absolute confirmation of it as yet exists. Pathology. Symptoms and Course. It is clearly ascertained from numerous reports founded on experience, that poisoning by Amanita phalloides and its varie- ties produces two groups of symptoms : one affecting the intesti- nal region, the other the nervous system. It may happen, from various accidental causes, that sometimes one group of symp- toms is more prominent, sometimes the other, but in general they are fairly balanced. The following cases may illustrate all 1 Journ. de Pharmaz. et de Chim. Juin. 1865. 5 Annal. d'Hyg. publique. Janvier, p. 71. 1867. 3 Des Champignons, etc. Paris. 1866. 940 VON BOECK.—VEGETABLE POISONS. that we know at present respecting this poison. In one casea the poisoning was of the gastro-intestinal type. A woman and her daughter were simultaneously poisoned; they were attacked with violent gastric pains and choleraic symptoms, to which the mother succumbed after fifty-two, the daughter after sixty hours. Goudot3 relates a case in which seven persons were poisoned by Hypophillum albocitrinicum. The symptoms appeared at the earliest twelve hours, at the latest twenty-nine hours after the introduction of the fungi. In the slighter cases the symptoms were diarrhoea and vomiting, with excessive thirst and sural cramps ; the consciousness remained undisturbed. In the severe cases vomiting, colic, diarrhoea, and convulsions appeared, with dejection, anxiety, slow and feeble pulse, which sank to fifty-six beats. Towards the approach of death, which did not supervene till after forty-eight or seventy-two hours, in one case seven days, after the poison had been introduced, general convulsions, tris- mus, loss of consciousness, and tetanus set in. In some cases, described by Maschka,' in addition to violent gastro-intestinal symptoms, general and partial convulsions, fainting, giddiness, delirium, somnolence, coma, etc., were observed. Taylor4 de- scribes a case of poisoning by Amanita citrina; a child died in convulsions on the second day, the mother died on the fifth day, with vomiting, diarrhoea, general insensibility and stupor. Olli- vier 6 relates of a physician at Batna (Algiers), that he and his family partook of mushrooms which had grown on a dunghill, which, however, were really Amanita bulbosa. The symptoms appeared about six hours after the meal, and fourteen hours after the first vomiting death supervened with marked cyanosis and tetanus. Carragon * reports the fatal poisoning of five French soldiers at Laon, who had partaken of a dish of mushrooms, 1 Empoisonnement par les Champignons. Journ. de Chim. med. p. 713. 1846. 2 Empoisonnement par les Champignons de sept personnes ; dont quatre guerisons et trois morts a Cubzy-les-soing (Haute Saone). Union med. No. 116. p. 466. 1852. 3 Einiges iiber Vergiftung mit Schwammen. Prager Viertetjahrschr. 1855. 2. Bd. p. 137. 4 Guy's Hosp. Report. Vol. XI. 16. 1866. 5 Journal de Chim. medic. 1868. e Gaz. des Hopit. 140. p. 1146. 1873. POISONOUS FUNGI.—RUSSULA INTEGRA. 941 really Amanita bulbosa. The symptoms of poisoning, which did not set in till eleven hours after the meal, were chiefly of a chol- eraic nature. Two died on the second day, two on the thud, and one not till the fifth day. As regards the results of autopsies, prognosis, diagnosis, treatment and test of the poisoning, what has been said of mus- carine-poisoning holds good generally for poisoning by Amanita phalloides and its varieties. We have only a few reports by Letellier and Speneux 2 of their experiments on animals; these were performed with the mixture which they obtained and called amanitine. Doses of a grain and a half (0.1) of Letellier's amanitin act poisonously upon frogs in ten to thirty minutes; with rabbits doses of fifteen grains (1.0) are necessary to produce torpor, stu- por, reduction of frequency of respiration, paralytic symptoms, coma, and finally death preceded by slight convulsions. When smaller doses are administered, recovery may set in after five to six hours. Cats are more sensitive than rabbits to this poison ; this circumstance is in favor of the supposed iden- tity between muscarine and the poisonous factor present in Amanita phalloide" Poisoning with Russula Integra and Boletus Luridus. Russula integra (Agaricus integer, Agaricus emeticus) has stiff lamellae ; is sapless, brittle, and of different colors—red, brown, violet, white, yellow, etc. Poisoning by means of this fungus was very frequent in former times; recently it has become extremely rare. The effect of it is a complication of strongly marked choleraic symptoms, which very soon terminate fatally. The result of autopsies corresponds to the clinical symptoms, which of themselves indicate the treatment. We have no accu- rate knowledge of the active constituent of the Russula integra; but we may conclude, from the fact that long cooking renders this fungus innocuous, whereas a rapid culinary process, such as 1 Annal. d'Hygiene publ. Janvier. 1867. 942 VON BOECK.—VEGETABLE POISONS. roasting, etc., fails to deprive it of its poisonous properties, that the poisonous factor is volatilized by the higher temperature. Boletus luridus (Boletus perniciosus, B. bovinus) has an olive green or brown cap (pileus), a firm, knobby, red stem ; it grows in summer and autumn in pine and other woods ; the flesh of the cap is white or yellowish ; when broken up it changes into dark blue (Husemann). This fungus also produces violent gastric and intestinal symp- toms—vomiting, diarrhoea, severe colicky pains, collapse, and convulsions—and the result is often fatal. Almen1 has obtained from Boletus luridus a substance which is apparently an alka- loid, and forms a precipitate with tannin. If this supposed alkaloid is really the poisonous principle of the boletus, its behavior toward tannin would be valuable in the treatment of this poisoning. In treating it, we must first endeavor to procure the elimination of the fungus from the intestinal canal, then attend to the collapse, respiratory and cardiac action, and also seek to relieve the subjective sufferings of the patient by administering opiates, etc. The symptoms produced by these fungi are very much the same as those which follow poisonings by the other varieties, so that what has been said above may be easily applied to the pos- sible action of other fungi. Poisoning with the Lower Forms of Fungi. ^ Partly for the sake of completeness, partly because poisoning with the lower forms of fungi may be regarded as a sort of tran- sition from intoxications, properly so called, to infectious dis- eases, which are nowadays generally attributed to small fungi, we may be allowed to devote a few words to cases of poisoning by the lower fungi. A frequent phenomenon in our ordinary victuals is the for- mation of mouldy fungi. Although it is a fact that human 1 Upsala Lakareforenings Forhandl. Bd. II. H. 4. p. 274. 18G8, MOULDY FUNGI. 943 beings may consume great quantities of such mouldy fungi with- out the slightest injury, yet examples are not wanting to prove that very violent attacks of illness, even death, may be the result of eating decayed food of this kind. Thus we have a recent account * of the poisoning of a family of three persons by eating mouldy bread ; they all suffered from colic, vomiting, and very violent convulsions. The adults recovered, but a little girl, five years of age, died of this poisoning. Boudier2 relates a similar case of a woman who, with her two children, had eaten cherries tainted by Vert-de-gris (Cladospo- rium herbarum). They became seriously ill, had violent gastric and intestinal pains, attacks of colic, vomiting, copious watery evacuations, coldness of the extremities, but recovered through the administration of opium and stimulants. These cases of poisoning closely resemble those produced by decayed mushrooms, and it is possible that, in the latter case, more weight ought to be attached to the decomposition of the food than to the actual fungi. Kennedy f communicates a remarkable case. A boy threw mouldy linseed in his schoolfellow's face with such violence that some of the seeds made their way into his eyes, his mouth, and even his larynx. He was attacked with severe pain, water- ing of the eyes, sneezing, coughing, dyspnoea, oedema of the face and eyelids. The next day fever set in, and an exanthem resem- bling measles, which soon disappeared, but the bronchitis and dyspnoea lasted for some time. It is very probable that it was the fungi which kept up the last symptoms so long. Till quite recently so-called hay fever or hay asthma, also called summer catarrh, was regarded as a pendant to the above- mentioned symptoms produced by the action of lower fungi, as a fungus was supposed to be the cause of this distressing catarrh, which often attacks people at the period of the ripening of mea- dow-grass and of the hay harvest. In support of the theory that fungi were the real cause of this malady, the case of Helmholtz 1 Pharmazeut. Zeitschrift fiir Russland. 1866. p. 572. 2 Des Champignons, etc. Paris. 1866. 3 Dubl. Quart. Journal. 1863. Feb. 944 VON BOECK.—VEGETABLE POISONS. was triumphantly cited. This distinguished scholar suffered long and repeatedly from hay fever, which usually attacks the same people every summer. Professor Binz, of Bonn, treated Helm- holtz with local application of solution of quinine, and the symp- toms of catarrh were ameliorated in a very short time, although a considerable time elapsed before complete recovery set in. Recently, however, we have been enlightened as to the true cause of hay fever, especially by the admirable treatise of Charles H. Blackley,1 who proved experimentally that the causa noxia was not a fungus, but certain pollen proceeding from various grasses, and which, when breathed in by persons unaccustomed to the open air, produces the symptoms of hay fever. When this pollen reaches the mucous membrane of the respiratory organs, it swells up, discharges its granular contents through the burst membrane, whereupon the liberated granula, by their lively movement, may produce catarrh. It is not yet decided whether some chemical irritation as yet unknown is at work or not, but it is very probable, as we know no analogous instance of the main- tenance of such persistent inflammatory symptoms, by a simple fine powdery organic substance. Hitherto we have no data what- ever for fixing upon this supposed chemical substance. Hay fever affords an example of the close connection between poison- ing and infectious diseases. For further details concerning hay fever, see Zuelzer's treatise upon it in this manual (Vol. II.). Dr. Miquel2 reports a similar form of disease produced by fungi (stilbosporei 1), a dust-like fungus, with poisonous action, which is developed on the old stem of Arundo donax. Peasants defend themselves against this dust by veiling their faces. If the fungus settles upon human beings, after twenty-four hours fever is set up, with gastric pains, weight and giddiness in the head, heat and burning in the face, upon which an exanthem appears in the form of vesicles and pustules. If the dust penetrates into the air-passages, violent coughing and dyspncea ensue ; if it en- ters the intestinal canal it produces colic, vomiting, and diar- ' Experimental Researches on the Causes and Nature of Catarrhus JEstivus (Hay Fever, Hay Asthma). London. 1873. - Note sur une maladie non encore decrite, communiquoe a l'homme par la Canne de Province. Bullet, general de therap., med., et chirurg. Juin. 1845. DUST-LIKE FUNGUS. 945 rhoea. The genitals also swell and become painful, so that saty- riasis and symptoms of nymphomania may be developed. Miquel relates four of these cases: one was that of a man sixty-one years of age, in whom the inflammation of the skin turned to gangrene, which put an end to his life. In general, the symp- toms soon disappear, and, with peeling of the skin, recovery sets in. Warm baths, oleaginous friction, laudanum, and cooling beverages proved to be beneficial and effectual in the other cases. Whether the symptoms in this disease are produced by an actual poison attaching to the fungus, or whether its form may not be the cause of the inflammatory processes, as in the case of the hair of certain caterpillars, e. g., the bear-worm, etc., is not yet ascertained ; we incline to the latter view. VOL. XVII.-60 INDEX. Abeilije, 685. Abortion a complication of poisoning by mercury, 614; by potassium nitrate, 375. Absinthe, Poisoning by, 412. Achscharumow, 751, 756. Acid in poisoning by ammonia, 366; in poisoning by caustic and carbonated alkalies, 370 ; hydrocyanic, in poisoning by atropine, 682; hydrosulphuric, inhalation of, in poisoning by chlorine, 290; min- eral, in scurvy, 235; phosphoric, in poisoning by opium, 876 ; sulphuric, dilute, in acute lead-poi- soning, 560 ; tannic, in poisoning by aconitine, 754 ; in poisoning by antimony, 621; in poisoning by atropine, 680 ; in poisoning by colchicine, 739; in poisoning by coniine, 820 ; in poisoning by del- phinine, 759 ; in poisoning by digitalis, 719; in poisoning by ergot, 902 ; in poisoning by nicotine, 772; in poisoning by opium, 866; in poisoning by strychnine, 794 ; in poisoning by veratrine, 731; in poisoning by zinc, 596; vegetable, in morbus maculosus, 278. Acid, Acetic, Poisoning by, 346. Acid, Carbolic, Poisoning by, 524. Acid, Carbonic, Poisoning by, 472. Acid, Citric, Poisoning by, 351. Acid, Hydrochloric, Poisoning by, 337. Acid, Hydrocyanic, Poisoning by, 498. Acid, Hydrofluoric, Poisoning by, 343. Acid, Nitric, Poisoning by, 340. Acid, Osmic, Poisoning by, 629. Acid, Oxalic, Poisoning by, 351. Acid, Phenilic, Poisoning by, 524. Acid, Prussic, Poisoning by, 498. Acid, Sulphuric, Poi=oning by, 322. Acid, Sulphurous, Poisoning by, 344. Acid, Tartaric, Poisoning by, 351. Ackermann, 714. Aconite in poisoning by strychnine, 800. Aconitine, Poisoning by, 744. Adelheim, 756. Adelmann, 40. Ae, 516. Aegineta, Paulns, 108. Agaricus Bulbosus, Poisoning by, 938. Age in etiology of haemophilia, 27; of morbus maculo- sus, 249; of scurvy, 122 ; influence of, upon mor- tality from chloroform, 426. Agnew, 684. Aitken, 163. Albers, 258, 758. Albin, 868. Albumen in poisoning by antimony, 024 ; in poisoning by arsenic, 651; in poisoning by copper, 592; in poisoning by iodine, 306; in poisoning by silver, 601; in poisoning by zinc, 596. Albuminuria in poisoning by alcohol, 405; in poison- ing by arsenic, 649; in poisoning by carbonic oxide, 468; in poisoning by lead, 583; in poison- ing by mercury, 615; in poisoning by phosphorus, 634; in poisoning by silver, 600 ; in scurvy, 165, 189. Alcohol, in poisoning by atropine, 6S5. Alcohol, Poisoning by, 3S2. Alcoholism, influence of, upon effects of chloral hy- drate, 449; upon mortality from chloroform, 429; upon sexual functions, 411. Alden, 853. Alexander, 375. Alfinger, 608. Alkalies in poisoning by sulphuric acid, 336. Alkalies, Poisoning by, 355. Alkaline salts, Poisoning by, 370. Allan, 10, 34, 50, 687. Allantiasis, 535. Alley, 609. Almen, 942. Alsaharavi, 5, 6, 20, 35. Alum in acute lead-poisoning, 560. Alum, Poisoning by, 379. Amanita phalloides, Poisoning by, 938. Amelung, 485. Ammann, 41. Ammonia, in poisoning by chlorine, 290 ; in poisoning by prussic acid, 511. Ammonia works, labor in, in etiology of poisoning by sulphuretted hydrogen, 493. Ammonia, Poisoning by, 355. Amory, 312, 314. 3EX. 948 ini Amy], nitrite of, in poisoning by ergot, 903. Amylene, Poisoning by, 453. Anaemia, a complication of haemophilia, 56; of mor- bus maculosus, 269; of poisoning by mercury, 610. Anderson, Th., 663, 683. Andral, 177. Andre, 33. Anilin and anilin dyes, Poisoning by, 519. Aniline, inhalation of, in poisoning by chlorine, 290. Anstie, 384, 400, 440, 441, 442, 443. Antimony, Poisoning by, 619. Apomorphia in poisoning by mercury, 605; in poison- ing by opium, 865 ; in poisoning by sulphuretted hydrogen, 497. Apoplexy following poisoning by alcohol, 409. Apoplexy in scurvy, 163. Aretaeus, 108. Argaing, 278. Arnal, 893. Arnet, S84. Arnold, W„ 785, 817. Aroneet, 299. Arnstein, 681, 700. Arsenic, Poisoning by, 644. Arseniuretted hydrogen, Poisoning by, 658. Arteries, changes in, in haemophilia, 53; in poison- ing by lead, 567; in poisoning by sulphuric acid, 335. Arthralgia saturnina, 574. Aschoff, 905, 90S. Ashamed, George, 801. Assmann, 41, 44, 45, 58, 73, 98. Astringents in haemophilia, 97; in scurvy, 238. Atlee, 779. Atmospheric influences in etiology of scurvy, 138. Atropine in poisoning by calabar bean, 704; in poi- soning by muscarine, 936 ; in poisoning by opium, 868; in poisoning by strychnine, 800. Atropine, Poisoning by, 661. Aurelianus, Caelius, 108. Autenrieth, 547, 548. Avicenna, 108, 561. Babington, 766, 774. Bachstroem, 131, 140. Bahrdt, 516, 517. Bailly, 893. Balard, 307. Bamberger, 639, 641. Banyer, 7, 20. Barbet, 288. Barclay, 368. Bard, Cephas J., 800. Bare, 846. Barium, Poisoning by, 375. Barker, Geo. P., 777, 780, 790. Barlow, 532. Barrier, 914, 918. Barruel, 349. Barthez, 249, 808, 380, 690. Bartholow, 681, 6S2. v. Basch, 768, 770, 900. Baskowen, 224. Bastik, 741. Baths in poisoning by lead, 573, 575, 579; in poison- ing by mercury, 619; sulphur, in poisoning by zinc, 597; warm, in poisoning by bromine, 321. Baudot, 384. Bauer, 235, 386, 387, 640, 664, 678, 700, 701, 702, 717, 862. Baxt, Waldemar, 843. Bazin, 304. Beatty, 901. Becker, Gustav Aime, 719. Beckler, 118, 127, 128, 221. Becquerel, 174, 175, 176, 177, 258. Beddoe, 661. Beer in scurvy, 223; barm of, in scurvy, 234. Behier, 368. Beigel, 830. Bell, 163. Benedictus, Alexander, 7, 11, 20. Benedikt, M., 297. 298. Bennet, B., 795, 815. Bennett, Hughes, 400. Benzin, Poisoning by, 512. Benzol, Poisoning by, 512. Bergeret, 594, 602. Bergeron, 514, 522, 616, 655. Bergmann, 514, 520, 521, 522, 523. Bergsten, 846, 874. Berkowsky, 548. Bernard, Claude, 291, 292, 388, 441, 456, 457, 458, 461, 472, 485, 488, 671, 768, 833, 835, 839, 843. Bernard, Paul, 303. Bernhardt, 480, 579. Bernstein, 672, 702, 715. Berolini, 19. Bert, 838. Berzelius, 307. Besserer, 55, 64. Beth, Tamme, 97. Betz, 485, 491, 496, 885, 890. Beyer, 86. von Bezold, 459, 671, 673, 674, 675, 676, 677. 6S1, 699. 700, 701, 702, 726, 728, 729, 730, 833, 834, 836, 870, 871. Bianchi, Attilio, 815, 816. Bichloride of ethylidene, Poisoning by, 454. Bichloride of methylene, Poisoning by, 453. Bidder, 834, 839. index. 949 Biermer, 492. Bietl, 258. Bill, 312, 313, 319, 525, 526. Billroth, 258, 425. Binz, 293, 294, 304, 313, 944. Birkett, 349, 350. Bismuth, subnitrate of, Poisoning by, 628. Bisulphide of carbon, Poisoning by, 477. Bitter almond oil, Poisoning by, 507. Bitters, the aromatic and pure, in scurvy, 234. Bjorkmann, 56. Black, 112. Blacke, 669, 724, 726. Blackley, Charles H., 944. Blagden, 10, 53, 54. Blake, 308, 340, 359, 370, 376. Blanc, 142, 205. Blanchard, 761. Blanchet, 437. Blank. 848, 875. Bias, 723, 725. Blasius, 713. Blasting-oil, Poisoning by, 533. Blatin, 801. Bleeder-disease. See under Haemophilia. Bloc, 828. Blochmann, 653. Bloebaum, 671, 673, 674, 675, 676, 677, 870. Blood, changes in, in haemophilia, 44 ; in morbus ma- culosus, 258; in poisoning by acetic acid, 349 ; in poisoning by ammonia, 359; in poisoning by bisulphide of carbon, 478; in poisoning by carbon- ic oxide, 469; in poisoning by sulphuretted hydro- gen, 486, in scurvy, 173. Blood, depletory transfusion of, in poisoning by car- bonic oxide, 472; in poisoning by prussic acid, 511. Blood-letting in morbus maculosus, 277; in poisoning by ammonia, 366 ; in poisoning by carbonic oxide, 471; in poisoning by opium, 867; in poisoning with strychnine, 803. Blood-vessels, condition of, in scurvy, 173. Boardley, 8. Bobrik, 347, 348. Boecker, 384, 387, 862. von Boeck, 294, 295, 386, 387, 616, 656, 717. von Boeck on Vegetable Poisons, 661. Boehm, 656, 657, 674, 682, 713, 714, 719, 727, 728, 751, 752, 758, 818, 936. Boehm on Poisons, 285. Boettcher, A., 418. Bogosslowsky, 932, 933. Bohn, 264. Boinet, 294. Boletus luridus, Poisoning by, 941. Bolley, 290. Bonassies, 667, 669. Bones, affections of, in poisoning by mercury, 611; in poisoning by phosphorus, 643 ; in scurvy, 162,169, 184 ; of medulla of, in morbus maculosus, 259. Bonjean, 846, 891, 914, 918. Bontekoe, 116. Bonwetsch, 385, 387, 418, 440. Borchard, 792. Borntraeger, 927, 933. Botkin, 676. Botulismus, 535. Bouchardat, 383, 605, C62. 665, 877. Bouchet, 235. Boudet, 368, 796. Boudier, E., 939, 943. Bouisson, 836. Boullay, 810. Bourdon, 235. Bourneville, 690, 691. Bouvier, 387, 420. Bowditch, 10, 312, 313, 316. Boyd, John S., 854. Brnin, affections of, in morbus maculosus, 254; in poisoning by aconitine, 753; in poisoning by al- cohol, 413 ; in poisoning by carbonic oxide, 470 : in poisoning by nicotine, 771. Braine, Woodhouse, 853, 855. Brambilla, 123. Brandes, 611, 757. Brandt, A., 720, 721. Braun, H., 673. Breuer, 423. Brewing trade in etiology of poisoning by sulpha- retted hydrogen, 493. de Brieret, 765. Briesemann, 896, 897. Brigstock, 41. Brockmann, 567. Brodie, 376. Bromine, Poisoning by, S06. Bronchitis following poisoning by carbonic oxide, 467; chronic, in poisoning by chlorine, 289. Brooks, Robert, 874. Brouardel, 2.33. Brown, 747, 750. Brown, Crichton, 365. Brown, Gosset, 679. Browne, 720. Brown-Sequard, 514, 522, 785. Brucaeus, 113. Brucine, Poisoning by, 810. Bruehlkramer, 407, 412. Bmnner, 421. Brunton, 714, Bryk, 286. Bryson, 205. DEX. 950 ini Buchheim, 293, 323, 324, 352, 354, 356, 358, 384, 607, 638, 716, 727, 763. Buchner, 435. Buckingham. 723. Bucquoy, 132. 233. Budd, 129, 338. Buel, 8, 37, 42, 44, 46. Bumpfield, 205. Bunge, 372. von der Burg, 808. Burkitt, 397. Burow, 780, 781. Buss, 55. Buttler, 375. Butzke, 308. Byasson, 446. Cabot, 668. Cadmium, Poisoning by, 594. Calabar bean in poisoning by atropine, 681; in poi- soning by strychnine, 801. Calabar bean, Poisoning by, 695. Callies, 501. Calvert, T. Crace, 663. Cameau, 123. Cameron, 233, 287, 288, 289, 696, 703, 704, 780. Camman, 58. Camphor in poisoning by alcohol, 415 ; in poisoning by strychnine, 802. Camus, 868. Cannabis indica in poisoning by opium, 876; in poi- soning by strychnine, 801. Canstatt, 125, 140, 247. Canuti, Canute, 235. Capsicum in poisoning by alcohol, 415. Carbolic acid, Poisoning by, 524. Carbon, bisulphide of, Poisoning by, 477. Carbon dioxide, Poisoning by, 472. Carbonated alkalies, Poisoning by, 366. Carbonic acid, diminished excretion of, following use of alcohol, 386. Carbonic oxide, Poisoning by, 456. Carler, 873. Carragon, 840. Carrignan, 868. Cartilages, affections of, in scurvy, 162, 169. Cartis, 130. Casper, 288, 324, 326, 333, 367, 368, 489, 496, 783. Castaldi, 685. Castan, 356, 261. Castell, 475. Catgut-making in etiology of poisoning by sulphu- retted hydrogen, 492. Cathartics in haemophilia, 97; in poisoning by arsenic, 651; in poisoning by atropine, 6S0 ; in poisoning by ergot, 902; in poisoning by fungi, 925; in poi- Boning by lead, 573; in poisoning by phosphorus, 641; in poisoning by santonin, 8S9 ; in poison- ing by sausages, 546; in poisoning by solanine, 695 ; in poisoning by strychnine, 795. Causse, Severin, 708. Caustic alkalies, Poisoning by, 366. Caustics in scurvy, 238. Caventou, 722, 775, T79. Cayrade, 758, 759. Cazaulvieilh, 341. Cejka, 118, 131, 144, 148, 172, 173, 186, 205, 206, 23S. Celsus, 108. Challand, 412. Chalvet, 135, 174,175, 176, 177, 197, 221. Chanet, 507. Charcoal, animal, in poisoning by atropine, 680; in poisoning by strychnine, 795. Charcoal, Poisoning by vapor of, 462. Charvet, 524. Chatanion, 874. Chatin, 690. Chedevergne, 383. Cheese, Poisoning by, 551. Chevallier, 298, 309, 829, 844. Chevers, Norman, 802. Chippendale, 796. Chloral in poisoning by alcohol, 414; in poisoning by lead, 573; in poisoning by picrotoxin, 813; in poisoning by strychnine, 799. Chloral hydrate, Poisoning by, 445. Chlorine in poisoning by strychnine, 596 ; in poison- ing by sulphuretted hydrogen, 497. Chlorine, Poisoning by, 2S5. Chloroform in poisoning by chlorine, 290: in poison- ing by picrotoxin, 813; in poisoning by strych- nine, 797. Chloroform, Poisoning by, 416. Cholmely, 316. Chrastina, 122. Christison, 289, 326, 337, 353, 354, 361, 380, 488, 591, 649, 654, 655, 697, 822, 823, 824, 847, 854. Chromium, Poisoning by, 626. Chrzonszewsky, 720. Churchill, 249. Cicatrization of tissues, effects of, following poison- ing by sulphuric acid, 332. Cicuta Virosa, Poisoning by, 827. Cider in scurvy, 223. Circulation, changes in, in poisoning by acetic acid, 348; in poisoning by alcohol, 388; in poisoning by ammonia, 359 ; in poisoning by bisulphide of carbon, 479; in poisoning by carbonic acid, 475; in poisoning by carbonic oxide, 458, 467 ; in poi- Boning by prussic acid, 504 ; in poisoning by sau- sage, 544; in poisoning by sulphuretted hydrogen, 488 ; in poisoning by sulphuric acid, 335 ; in poi INDEX. 951 Boning by sulphurous acid, 345; changes in organs of, in haemophilia, 53. Circumcision, prohibition of, in haemophilia, 94. Clarke, 312, 314. Clarus, 692, 693. Clay, 10. Cleanliness in scurvy, 224, 228. Clemens, Th., 491, 496, 497. Clemenz, B., 417. Climate in etiology of scurvy, 138. Cloetta, 809, 878. Cloez, 478. Clothing, proper, in scurvy, 224. Coale, 127. Coal-gas, labor in manufacture of, in etiology of poi- soning by sulphuretted hydrogen, 493. Coal-gas used for illuminating purposes, Poisoning by, 464. Coates, Reynell, 10, 34, 43. Cochrane, 10. Cod-liver oil in haemophilia, 96. Coffee in poisoning by opium, 866. Cohn, 687. Cohnheim. 129. Coindet, 353. Colchicine, Poisoning by, 734. Coniine, Poisoning by, 815. Connective tissue, affections of, in morbus maculosus, 255; in scurvy, 155, 168, 183. Consbruch, 8, 36, 97. Convulsions in poisoning by anilin, 523 ; in poisoning by antimony, 621; in poisoning by arsenic, 648; in poisoning by atropine, 669; in poisoning by bi- sulphide of carbon, 482; in poisoning by carbolic acid, 530 ; in poisoning by carbonic oxide, 466; in poisoning by coniine, 816; in poisoning by cop- per, 591; in poisoning by cystisine, 824; in poi- soning by digitalis, 710 ; in poisoning by ergot, 908; in poisoning by fungi, 940 ; in poisoning by lead, 566, 570, 582 ; in poisoning by mercury, 612; in poisoning by nicotine, 769 ; in poisoning by ni- tro-benzin, 517 ; in poisoning by phosphorus, 633; in poisoning by picrotoxin, 811; in poisoning by prussic acid, 502, 510; in poisoning by santonin, 885 ; in poisoning by solanine, 693; in poisoning by strychnine, 780; in poisoning by sulphuretted hydrogen, 495; in poisoning by sulphuric acid, 329 ; in poisoning by veratrine, 725. Cooper, 235. Cooper, Stuart, 665. Copeland, 798. Copland, 763. Copper, Poisoning by, 589. Copper, sulphate of, in poisoning by phosphorus, 641. Corbet, 848. Cosserat, 928, 929. Cough in poisoning by chlorine, 289. Coullon, 501. Courtay, 688. Courton, 338. Cousins, 41. Coxe, 8, 40. Cramer, 672. Cuming, 401, 408, 414. Cupping, dangers attending, in haemophilia, 95. Curan, Waring, 415. Curare in poisoning by strychnine, 796. Curarine, Poisoning by, 830. Curran, 249, 278. Cyon, 352, 376. Cystisine, Poisoning by, 822. Czermak, 671. Dagtjbnbt, 410. Damourette. 314, 817. Daniel, 885. Daniell, Fr., 489. Danielli, 688. Danilewsky, 807, 818. Danvin, B., 777. Darbel, 758. Darby, 795. Daub, 387. Davies, Th. G. D., 790. Davis, 10, 37. Davy, 808. Davy, Humphrey, 454. De Anna, 359. Decaisne, 766. Dechambre, 113. Defosses, 689. Dehaen, 654. Delfort, 205. Delirium tremens, 400. Delpech, 113, 132, 478, 479, 480, 481, 482, 483, 484. Delphinine, Poisoning by, 757. Demarquay, 887, 485. Denis, 177. Dequevauviller, 10, 35, 46. Dessault, 763. Deutsch, 368, 392, 396, 398, 688, 764, 767, 772. Devergie, 496. Dewar, 868. Diabetes mellitus following poisoning by carbonic oxide, 468. Diagnosis. See Different Diseases. Diakonow, 486, 487. Diet in hemophilia, 96 ; in morbus maculosus, 279 ; in poisoning by alcohol, 415 ; in poisoning by mercury, 618; in scurvy, 218, 228; articles of, and bad preparation of, in etiology of copper-poison- ing, 590; in etiology of scurvy, 125. 952 index. Diet, Poisoning by tainted articles of, 535. Di-ethel ether, Poisoning by, 439. Dieudonne, 288. Diez, 309. Digestion, effects of alcohol upon, 388. Digitalis in haemophilia, 97. Digitalis in poisoning by aconitine, 755; in poisoning by alcohol, 414. Digitalis, Poisoning by, 706. van Dissel, 855. Ditzel, 905. Dobie, 747, 755. Dodeuil, 871. Dodonaeus, 113. Doellinger, 817. Doepp, 122. Doepping, 921. Doering, 114, 136. Dogiel, 423, 672, 702. Donuers, 457, 668, 679. Donyan, 848. Dor, 699. Dorn, 758. Dougall, John, 846. Drachmann, 634. Dragendorff, 686, 687, 688, 705, 720, 721. 731,732, 739, 740, 741, 755, 756, 773. 774, 775, 806, 807, 808, 809, 820, 840, 877, 878, 879, 880, 881, 882. Drawitz, 116. Dropsy in poisoning by arsenic, 655; in poisoning by mercury, 614. Dubois, 10, 41, 58. Duchek, 112, 118, 122, 123, 125, 128, 129,134, 136, 140, 14!, 146, 148, 160, 163, 165, 16!, 172, 175, 187,190, 191, 290, 205, 206, 220, 221, 234, 334, 851. Duffield, 309. Dumas, 760, 796. Dumeril, 387. Dupre, 384. Duquesnel, 745. Duriau, J., 782. Duroy, 383, 384, 385, 387, 395. 417, 438. Dust-lilJe Fungi, Poisoning by, 944. Dwelling-places, unhealthy, in etiology of scurvy, 137. Dybkowsky, 713. Dysentery in etiology of scurvy, 122. Dysphagia in poisoning by alum, 381; in poisoning by atropine, C66, 669; in poisoning by caustic and carbonated alkalies, 368. Dyspnoei in poisoning by chlorine, 289. Dzondi, 606. Ear symptoms in poisoning by alcohol, 402; in poi- soning by atropine, 666; in poisoning by barium compounds, 379; in poisoning by bisulphide of carbon, 481; in poisoning by carbonic oxide, 465; in poisoning by ergot, 909. Earthy salts, Poisoning by, 370. Easton, 747, 750. Eberty, 896, 897. Ebner, 804. Echtius, 113, 117, 123. Edwards, 706. Egede, 219. Eisenmenger, 716, 727. Electricity in poisoning by aconitine, 755; in poison- ing by bisulphide of carbon, 484 ; in poisoning by carbolic acid, 532; in poisoning by carbonic oxide, 471; in poisoning by chloroform, 438 ; in poison- ing by lead, 575, 579; in poisoning by mercury, 619. Elsaesser, 9, 37, 46, 64, 100. Emaciation in poisoning by acetic acid, 351; in poi- Boning by lead, 565. Emetics in poisoning by aconitine, 754 ; in poisoning by arsenic, 651; in poisoning by atropine, 680 ; in poisoning by calabar bean, 704 ; in poisoning by cicuta virosa, 827 ; in poisoning by cystisine, 82(5; in poisoning by delphinine, 759; in poisoning by digitalis, 719; in poisoning by ergot, 902 ; in poi- soning by fungi, 925, 935; in poisoning by lead, 560 ; in poisoning by nitro-benzin, 519; in poison- ing by opium, 865; in poisoning by phosphorus, 641; in poisoning by picrotoxin, 813; in poison- ing by santonin, 889; in poisoning by solanine, 695; in poisoning by strychnine, 794; in poison- ing by veratrine, 731. Emmert, 501. Emminghaus, 485, 491. 406. Encephalopathia Saturnina, 581. Engelhardt, 703. Epilepsy following poisoning by alcohol, 410. Erb, 578, 587 Erdmann, J., 808, 881. Ergot in haemophilia, 97 ; in morbus maculosus, 278; in scurvy, 235. Ergot, Poisoning by, 890. Erhardt, 882. Erlenmeyer, 869, 871, 872. Escherich, 83. Eserine, Poisoning by, 695. Esmarch, 574. Espagne, 368. Esquirol, 407. Ether, sulphuric, Poisoning by, 439. Ethylidene, bichloride of, Poisoning by, 454. Etiology. See Different Diseases. Eugalenus, Severinus, 115, 116. Eulenberg, 286, 287, 314, £38, 342, 344, 345, 360, 462, 476, 485, 490, 492, 520, 572, 587, 642, 712, 760, 761- ind: Evans, 668, 670, 698, 697, 704, 749, 750. Ewald, 517, 518. Exercise, physical, in poisoning by opium, 866; exces- sive physical, in etiology of scurvy, 139 ; want of physical, in etiology of scurvy, 141. Eye symptoms in poisoning by aconitine, 750, 752; in poisoning by alcohol, 394, 402, 410; in poisoning by arsenic, 654; in poisoning by atropine, 666, 663, 672; in poisoning by barium compounds, 379; in poisoning by bisulphide of carbon, 481; in poisoning by bromine, 319; in poisoning by calabar bean, 697 ; in poisoning by carbolic acid, 530; in poisoning by carbonic oxide, 464; in poi- soning by cheese, 552; in poisoning by coniine, 816; in poisoning by curarine, 832; in poisoning by cystisine, 824 ; in poisoning by digitalis, 710; in poisoning by ergot, 893, 908 ; in poisoning by fish, 550; in poisoning by helleborin, 742; in poison- ing by iodine, 303 ; in poisoning by lead, 582; in poisoning by muscarine, 932; in poisoning by nitro-benzin, 517 ; in poisoning by nitroglycerine, 534 ; in poisoning by opium, 850; in poisoning by prussic acid, 509; in poisoning by santonin, 883; in poisoning by solanine, 691, 693; in poison- ing by sausage, 543 ; in poisoning by strychnine, 782, 790 ; in poisoning by veratrine, 725; in scur- vy, 164, 205. Faber, 539. Fabius, 496. Fageret, 767. Falck, 323, 395, 485, 594, 811, 889, 890, 904, 914. Falk, 2S6, 287, 758. Fah-et. 321. Farquharson, 884. Farrington, 875. Fats in poisoning by strychnine, 795. Fauvel, 118, 122. Favre, 177. Feltz, 447. Feneulle, 757. Ferric hydrate in poisoning by arsenic, 651. Ferrier, 530. Fever in morbus maculosus, 260 ; in poisoning by alcohol, 404 ; in poiponing by phosphorus, 633 ; intermittent, in etiology of scurvy, 122. Ficinus, 823. Fick, 727. Finger, 45, 56, 94. Fink, 234. Finlay, 855. Fischer, 53, 54. Fischer, George, 822. Fish, Poisonous, 547. Fistulas following poisoning by sulphuric acid, 333. ex. 953 Flandin, 878. Flax-steeping in etiology of poisoning by sulphuretted hydrogen, 492. Flechner, 665, 745, 747, 748, 816. Fleck, 653. Fleming, 673, 675, 747, 748, 856, 875. Fletcher, 523. Flinzer, 906. Flourens, 442. Fly-fungus, Poisoning by, 926. Foetus in utero, action of ergot upon, 900. Folker, W. H., 781. Foltz, 123. Fonssagrives, 364. Fontana, N., 112. Fordyce, 6, 8, 34, 100. Forest, 735, 736. Fothergill, 415. Fournet, 308. Foville, A., 400, 407. Fraas, 692. Fraser, 677, 696, 697, 698, 699, 702. Frazer, C81. Freusberg, A., 788. Friedberg, 456, 458, 467, 463, 470, 471, 472. Friedel, 112, 205, 206 Fries, 480, 484. Froehlich, 072, 674, 700, 868, 869. Froelieh, 682, 870. Frommhold, 684, 868, 873. Fronmueller, 692, 693, 696. FuchF, 247. Fuller, H. W., C63, 795, 800. Fungi, Poisoning by, 920. Funke, 359. Gaehtoens, 502, 503. Gaillard, 794. Gairdner, 298, 400. Galezowski, 410. Gall, 421. Oallaher, 867. Gallavurdin, 761. Gangrene following poisoning by alcohol, 396 ; by er- got, 914. Garelli, 646. Garrod, 131,133,135, 175, 191, 194, 196, 197, 200, 567, 680, 795. Gastric juice, effect upon secretion of, by alcohol, 388. Gas-works, labor in, in etiology of poisoning by sul- phuretted hydrogen, 493. Gatumeau, 319. Gavarret, 177. Gavoy, 45, 63, 54, 55. Gay, E., 790, 807. Geiger, 601, 688, 744, 814. )EX. 954 INI Geographical distribution of haemophilia, 12; of scurvy, 118. Gerard. 937. Gibbon, 894. Giesecke, 814. Gillespie, 298, 800. Giraud, 724. Gleaves, 621. Glonoin, Poisoning by, 533. Glover, 307, 308. Gmelin, 370, 763. Goetz, 681, 699, 700, 701, r02. Gold, Poisoning by, 628. Goltz, 348, 898. Gottwald, 501. Goudot, 940. Gout, a complication of chronic lead-poisoning, 567. v. Graefe, 684, 703, 869. Graham, 822. Grainger, 857. Grandean, 371. Grandeau, 720. Grandidier, 6, 9, 10,13, 15, 16,19, 21, 23, 25, 26, 27, 28, 29, 30, 32, 34, 36, 37, 41, 42, 47, 48, 50, 53, 56, 57, 58, 59, 61, 84, 85, 91, 97, 99, 100, 101, 103. Graves, Thomas Thatcher, 873, 868. Gray, J. St. Clair, 747, 755, 794. Grenet, 113. Griepenkerl, 920. Griesinger. 408. Grimm, 883, 885. Grohe, 623. Gross, 664. Gross, Heimann, 893. Grossheim, 94. Gruenhagen, 673, 702, 770. Gscheidlen, 699, 858, 859, ?60, 870, 871. Gubler, 446, 663. Guenkel, 813. Guerard, 338. Gull, W., 513. Gums, changes in, in poisoning by copper, 593: in poisoning by lead, 565; in poisoning by silver, 600, 611; in scurvy, 147,170,180. Gunning, 631. Gusserow, 560. Guttmann, 314, 372, 514, 515, 726, 817, 818. Guyot, 520. Haemophilia, 3 ; bibliography,.3 ; history, 5; defi- nition, 13 ; etiology, 15 ; description of the disease and symptomatology, 38 ; external hemorrhages, 39 ; interstitial bleedings, 46; anatomical changes, 52; complications and sequelae, 55 ; nature and pathogenesis, 60; diagnosis, 78; duration and terminations, 82; prognosis, 86 ; treatment, 88. Haemoptysis following poisoning by carbonic oxide, 467. Haemorrhagic Idiosyncrasy. See under Haemophilia. Haemorrhophilia. See under Haemophilia. Hafner, 734 Hainworth, 530. Halfort, 288. ffameau, 321. Hamilton, 798. Hammarston, 446, 447. Hammer, 856. Hammond, 766. Hare, 682. Harley, 783, 785, 795, 804, 869. Harnack, 703, 927. Harris, 32. Harting, 632. Hartmann, 638. v. Hasselt, 287, 288, 298, 326, 381, 476, 488, 489, 495, 497, 548, 564, 591, 620, 625, 631, 632, 757, 886, 888. Haudelin, 896, 897. v. Hauff, 635. Hawkins, 856. Hay, 8, 19, 20, 43, 84. Hayden, 675. Hayem, 113. Headache in poisoning by aconitine, 749, 751; in poi- soning by anilin, 523; in poisoning by bisulphide of carbon, 481; in poisoning by carbonic oxide, 464; in poisoning by cheese, 552; in poisoning by curarine, 831; in poisoning by cystisine, 823 ; in poisoning by digitalis, 709 ; in poisoning by er- got, 893 ; in poisoning by nitro-glycerine, 634 ; in poisoning by santonin, 885; in poisoning by vera- trine, 724. Health, influence of, upon mortality from chloroform, 427. Heart, action of aconitine upon, 749; of alcohol, 388; of arsenic, 650; of atropine, 666, 674 ; of barium compounds. 376 ; of calabar bean, 697 ; of chloral hydrate, 448; of chloroform, 421; of colchicine, 735, 737 ; of digitalis, 710 ; of ergot, 893, 908; of helleborin, 742; of muscarine, 931; of nicotine, 768, 771; of opium, 858 ; of phosphorus, 633 ; of picrotoxin, 812 ; of potassium salts, 372 ; of prus- sic acid, 504; of santonin, 885 ; of sausage-poi- soning, 544; of sulphuretted hydrogen, 448; of sulphuric ether, 441; of veratrine, 724, 729; af- fections of, in haemophilia, 54; in morbus ma- culosus, 258; in scurvy. 171; influence of disease of, upon mortality from chloroform, 429. Heath, 85. Hebra, 245. Heidenhain, 671, 702, 833. Heiemerdinger, 308. Heine, 348, 349. INDEX. 955 Heinemann, 788. Helbig, 516. Helleborin, Poisoning by, 741. Hellmann, 689. Helm, 915. Helmholtz, 887. Helwig, 756, 809, 821. Hememvfiy, 781, 784, 801. Hemorrhage in morbus maculosus, 254, 259; in poi- soning by iodine, 305; in poisoning by opium, 850 ; in poisoning by phosphorus, 633 ; in scurvy, 160,185 ; arrest of, in haemophilia, 97; in etiology of scurvy, 122. Hemorrhagic diathesis. See under Haemophilia. Henderson, 233. Henkel, 288, 488, 548. Henoch, 235, 248, 255, 256, 269. Henschel, 94. Herard, 269. Heredity in etiology of haemophilia, 15. Hergott, 349, 350. Hermanides, 898. Hermann, 286, 298,301, 305, 306, 391, 401, 415, 419, 420, 446, 447, 4r-4, 474, 475, 478, 586, 605, 622, 702, 804, 897. Hermann, L., 673, 839. Hermbstaedt, 485, 661. He we, 661, 688, 695, 744. Heubel, 291, 292, 562, 583, 584, 585, 586. Heusinger, 906. Heward, 778. Heydloff, 883, 884. Heyfelder, 35, 61, 96. Heyland, 45. Heymann, 12. Himmelstiern, 118, 165, 172, 186, 187, 234. Hinkeldeyn, 823, 824, 825. Hippocrates, 108, 109. Hirsch, 108, 113, 114, 117, 118, 119, 123, 125, 126, 129, 130, 131, 134, 138, 451 Hirschmann, 673, 702. Hirt, 2S7, 2S9, 290, 344, 345, 346, 359, £60, 478, 479, 726, 728, 729, 730. His, 76. History. See Different Diseases. Hitzig, 561, 584. Hoechstetter, Philipp, 7, 11, 20. Hoegh, 767. Hoelder, 324. Hoering, 308. Hoffmann, 526. Hoffmann, F. A., 513. Hoffmann, Fr., 116. Hohl, 99. Holmes, 897. Holmgren, 423. i Holthouse, C, 666, 635. Homolle, 706, 7G7, 721, 722. Honssell, 596. Hooper, 53, 54. Hoppe, J., 837. Hoppe-Seyler, 457, 458, 469, 486, 487, 488, 502, 525, 537. Horn, 113. Horst, 123. Hottot, 752. Houghton, 784, 802. Hubler, 737. Huebner, 486. Huobschmann, 744. Huefner, 887. Hufeland, 305, 883. Hughes, 10, 35. Hulme, 205. Hunt, 249. Hunter, William, 778, 781, 784. Husemann, 295, 298, 306, 309. 312, 316, 324, 336, 341, 343, 344, 346, 349, 353, 354, 355. 376, 381, 423, 446, 451, 454, 456. 464, 476, 4S8, 496, 497, 499, 507, 516, 523, 526, 527, 529, 531, 532, 533, 534, 536, 538, 539, 542, 552, 553, 559, 623, 628, 661, 662, 688, 692, 693, 695, 696, 744, 745, 763, 778, 805, 808, 828, 846, 847, 856, 857, 868, 880, 881, 887, 891, 923, 927, 933, 934, 938, 942. Husemann, A., 741, 742, 821, 822. Husemann, Th., 800. Hutchinson, 766. Hyde, 61. Hydrate of phenyl, Poisoning by, 424. Hydrated ferrous sulphide in mercurial poisoning, 605. Hydrogen, sulphuretted, Poisoning by, 484. Hyoscyamine in poisoning by strychnine, 800. Hyoscyamus, Poisoning by, 688. Icterus in poisoning by copper, 591; in poisoning by phosphorus, 633, 643. Ihmsen, 817. Immermann on Haemophilia, 3; on Morbus Maculo- sus Werlhofii, 243 ; on Scurvy, 105. India-rubber factories, labor in, in etiology of poison- ing by sulphuretted hydrogen, 493. Infarction, hemorrhagic, a complication of scurvy, 204. Injury in etiology of haemophilia, 33. Intestinal symptoms in morbus maculosup, 256, 265, 269; in scurvy, 172, 185, 204; in poisoning by acetic acid, 350 ; in poisoning by aconitine, 750; in poisoning by alcohol, 394 ; in poisoning by al- kalies, caustic and carbonated, 369; in poisoning by antimony, 621; in poisoning by arsenic, 648, (154 ; in poisoning by barium, 376 ; in poisoning by bisulphide of carbon, 482 ; in poisoning by cal- 956 INDEX. abar bean, 60S; in poisoning by cheese, 552; in poisoning by chromium, 627 ; in poisoning by col- chicine, 735, 737; in poisoning by copper, 593 ; in poisoning by cystisine, 824; in poisoning by digi- talis, 709; in poisoning by ergot, 893, 907, 915; in poisoning by fish, 550 ; in poisoning by fungi, 923, 929, 940 ; in poisoning by helleborin, 742: in poi- soning by iodine, 300 ; in poisoning by iron, 625 ; in poisoning by lead, 559, 566, 571 ; in poisoning by mercury, 604, 610; in poisoning by nicotine, 764; in poisoning by opium, 856, 875 ; in poison- ing by phosphorus, 632; in poisoning by potassium nitrate, 374; in poisoning by sausage, 542; in poisoning by silver, 599 ; in poisoning by solanine, 691; in poisoning by sulphuretted hydrogen, 494 ; in poisoning by veratrine, 724; in poisoning by zinc, 597. Iodine in poisoning by aconitine, 754; in poisoning by atropine, 680 ; in poisoning by strychnine, 795. Iodine, Poisoning by, 290. Ipecac in haemophilia, 97. Iron, Poisoning by salts of, 624. Iron, preparations of, in haemophilia, 96; in morbus maculosus, 278; in scurvy, 235. Irritants in poisoning by carbonic oxide, 471. Jackson, 437. Jeffrey, 530. Jenner, 662. Jervine, Poisoning by, 733. Jettelet, 744. Jobert, 914. Jochelsohn, 776, 804, 806. Joeig, 297. Johannson, 774. Johnson, 316, 338, 339, 746. Johnston, James, S55, 874. Joints, affections of, in haemophilia, 57; in morbus maculosus, 257, 264; in scurvy, 162, 169, 184; in poisoning by lead, 574. JoinviUe, 109, 160. Jolly, 451. Jolyet, 737. Juergensen, 280. Junker, 453. Kaemmerer, 293, 294, 295. Kane, Smiley, 828. Kaufmann, 484, 485, 486, 488. Kaupp, 803. Kauzmann, 878, 879, 882. Keber, 922. Keen, 6S2. Keen, W. W., 869, 871. Keller, 735. Kellok, 847. Kenan, 931. Kendrick, 10. Kennard, 734, 736. Kennedy, 765, 943. Kerner, Justinus, 536, 537, 539. Kersch, 875. Keuchel, 671, 674, 676, 677. Kidd, 429, 430. Kidneys, affections of, in poisoning by aconitine, 753; in poisoning by alcohol, 388, 413; in poisoning by carbonic oxide, 470 ; in poisoning by digitalis, 718; in poisoning by iodine, 306 ; in poisoning by lead, 567, 583; in poisoning by nicotine, 771; in poi- soning by phosphorus, 635; in poisoning by sil- ver, 60C ; in poisoning by sulphuric acid, 335; in scurvy, 172, 204. Kieter, 548. Klebs, 458, 459, 460, 461, 464, 467, 470, 472, 636. Knagges, 523. Knie, 503, 682. Knieriem, 357. Koch, 548, 746, 753, 839, 840. Koehler, 528, 422, 641. Koelliker, 499, 726, 728, 785, 817, 834 Koeppen, 338. Koerner, 684, 687. Kohlrausch, O., 922. Kohn, 684. Koning, 870. Kopp, 96. Koppe, Robert, 707, 926, 930, 933, 936, 937. Kosmann, 706. Krahmer, 376. Kramer, 116. Krause, 347. Krauss, 890. Krebel, 107, 112, 113, 118, 122, 141, 163, 165, 173, 187, 205, 219, 222, 224, 234, 239. Kremiansky, 389, 413. Krenchel, 932. Kreuser, B., 517. Krimer, 9, 36, 43, 61, 501. Krischker, 122. Krocker, 769, 770. Kuehne, 471. 500. Kuerner, 678. Kuerschner, 501. Kuess, 304, 805. Kuethe, 6C4, 669. Kuettner, 2C5, 206. Kuhl, 9. Kuhorn, 663. Kunde, 804. Kunze, 656. Kurzack, 795. Kussmanl, 270, 567, 573, 608, 609, 613, 614, 616, 61P, 927, 933. INDEX. 957 Laborde, 316, 705. Laboulbene, 176. Laennec, 620. Laf argue, 10. Lailler, 520, 522, 52:5. Lallemand, 383, 384, 385, 3S7, 395, 417, 438, 440. Lancelot, 706. Lancereaux, 413, 567, 579. Landerer, 762. Landois, 642. Landrin, 520. Lane, 10,101. Lange, 9, 356, 357, 358, 359. Langenbeck, 898. Larrey, 123. Larynx, affections of, in poisoning by atropine, 60S. Laschkewitsch, 626, 698, 699, 700. Lasegue, 113, 132, 173, 176. Lassaigne, 757, 877. Laughing gas, Poisoning by, 454. Laurenzo, Jos., 662. Lauzer, Chassaignac, 662. Law, 249. Laycock, 400. Leach. 77S. Lead, acetate of, in haemophilia, 97; in morbus macu- losus, 278. Lead Colic, 570, Lead Paralysis, 576. Lead, Poisoning by, 557. Lead-works, labor in, in etiology of chronic lead-poi- soning, 561. Lebedeff, 628. Lebel, 868. Lebert, 10. Lebourdais, 706. Lecorche, 682. Lev, 131. Lee, C. C, 663, 684. Lefort, 877. Legg, Wiokham. 7, 9, 10, 26, 33, 89, 96, 97, 685. Legrand, 258, 298. Legroux, 113, 121, 132, 173, 176. Lehmann. 291, 348, 45S, 460, 466, 656. Lehwald, 291, 562, 622. Leischmann, 26S, 369. Lemaire, 525, 52S. Lemaitre, 616. Lemattre, 655, 674, 686. Lemon-juice in scurvy, 22. de Lemos, Ferreira, 830. Lemp, 41, 50. 54. 85. Lenz, 421, 700, 701. Leroux, 709. Lersch, 710, 772. Letellier, 939, 941. Letheby, 514, 515, 516, 517, 51& Leube, 803, 804, 806. Leudet, 466. Leudike, 336. Leutholdt, 257. Leveille, 163. Leven, 705. Lewizky, 314. Leyden, 325, 331, 348. Leydorff, 692. Leygey, 063. Lichtenfels, 663. Lieberkuehn, 593. 598, 600. von Liebig, J.. 134, 384, 386, 486. Liebreich, 420, 445, 446, 454, 799. Liegard, 368. Liegeois, 752. Lilienfeld, 118. Lime, Poisoning by, 370. Lime, preparations of, in poisoning by oxalic acid, 355. Lind, 110, 111, 115, 116, 117, 123, 129, 219, 239. Lindbeck, 56. Linden, 696. Lindwurm, 56. Linstow, 883. Lion, 370. Lionville, 831, 833. Lipowitz, 630. Lissonde, L., 446. Listen, 53. Liver, affections of, in poisoning by alcohol, 413; in poisoning by arsenic, 650; in poisoning by car- bonic oxide, 470; in poisoning by digitalis, 718; in poisoning by nicotine, 771; in poisoning by phosphorus,633, 635; in poisoning by silver, 6)0; in poisoning by sulphuric acid, 335; in scurvy, 172. Logan, 119. 127. Lohrer, 356, 357. Lohrmann, 883, 885. Lonsdale, 777. Lopez, 662. Lorentenz, 681. Lonfflet, 278. Lowthorps, 97. Ludlow, 857. Ludwig, 671. Lungs, affections of, in poisoning by aconitine, 753; in poisoning by carbonic oxide, 467 ; in poisoning by nitric acid, 343; in poisoning by sulphurous acid, 345; in scurvy, 171. Lupuline in poisoning by opium, 876. Lusanna, 665. Lyons, 846. 958 INDEX. Macdonald, Angus, 799. Machin, 528. Mackenzie. 523. Maclagan, McGregor, 734. Magendie, 297, 622, 803. Magnan, 3S9, 395, 402, 404, 410, 412. Magne, 690. Magnesia in poisoning by arsenic, 651; in poisoning by barium compounds, 379; in poisoning by cop- per, 592 ; in poisoning by lead, 560 ; in poisoning by oxalic acid, 355; in poisoning by sulphuric acid, 336. Magnus, Olaus, 113, 117. Magron, 836. Mainzer, 387. Majer, 809. Malarial disease in etiology of scurvy, 122. Maly, 828. Mammary gland, atrophy of, in poisoning by iodine, 305. Manganese, Poisoning by, 626. Manners, 690. Mannkopf, 324, 325, 331, 332, 636, 637, 719, 776. Manns, 889. Mannson, 797. Manouvriez, 564. Marcellus, 108. Marcet, 415. Marchand, 808. Marchant, 762. Marme, 628, 741, 742, 743, 821, 822, 823, 825, 826, 827. Marriage, question of, in haemophilia, 88. Marsh, 045. Marsh, H, 249. Marston, 401, 402. Martin, 9, 36, 50, 96, 444, 761. de Martini, 884. Martino, G., 662. Maschka, 790, 933, 934, 940. Masing, 3S4, 732, 806, 807. Maury, 690. Mayencon, 594, 602. Mayer, 270, 621. Mayer, Heinrich, 358, 785. Mayer, S., 787, 788, 900. Mayerhofer, 620. Mazel, 708, 710. M'Cormack, 691. McPherson, 790, 858. Mead, 116. Meckel, 64. Mogevand, 717. M6hu, 569, 639, 640. Meihuizen, 716. Meikle, John, 802. Mein, 661. Meinel, 9, 44, 50, 64,100. Melier, 760. M> lion, 349. Melseus, 292, 568, 597, 774. Membranes, mucous, affections of, in morbus maculo- sus, 254 ; in poisoning by acetic acid, 349; in poi- soning by aconitine, 748, 750; in poisoning by alcohol, 413; in poisoning by alkalies, caustic and carbonated, 368 ; in poisoning by alum, 381; in poisoning by ammonia, 357; in poisoning by ani- lin, 523 ; in poisoning by antimony, 623 ; in poi- soning by arsenic, 649; in poisoning by carbolic acid, 531; in poisoning by carbonic oxide, 466; in poisoning by chlorine, 287; in poisoning by cor- rosive sublimate of mercury, 604 ; in poisoning by hydrochloric acid, 339; in poisoning by iodine, 303; in poisoning by nicotine, 771 ; in poisoning by nitrate of silver, 600; in poisoning by phospho- rus, 635; in poisoning by potassium nitrate, 375 ; in poisoning by sausage, 544 ; in poisoning by sul- phuric acid, 334; in poisoning by veratrine, 726 ; in poisoning by zinc, 596; in scurvy, 147, 170, 180; serous, affections of, in morbus maculosus, 254 ; in scurvy, 161. Mendel, 394. Menstruation, disorders of, in poisoning by bisulphide of carbon, 4S2 ; in poisoning by iodine, 305. . Mental depression in etiology of scurvy, 141. Mercier, 304. Merck, G., 722, 723. Mercury, Poisoning by, 601. Merie, 435. Merkel, 40. Mertens, 219. Methylene, bichloride of, Poisoning by, 453. Meuriot, 675, 682. 686. Meyer, 567, 573, 714, 764, 827. Meyer, Lothar, 457. Meyer, M., 561. Meyer. S., 835. Meyern, V., 761. Meyhuyzen, 598. Mialhe, 615. Michaelis, 528, 594, 597, 598. Michel, 568. Mickwitz, 370, 372, 377. Micturition, difficult, in poisoning by atropine, 666. Mignot, 278. Milanesi, 295. Miling, 35. MUk in poisoning by antimony, 624 ; in poisoning by arsenic, 651; in poisoning by lead, 560 ; in poison- ing by mercury, 605; in poisoning by silver, 601; in poisoning by zinc, 596. Milman, 125. INDEX. 959 Mining, labor at, in etiology of poisoning by sulphur- etted hydrogen, 493. Miquel, 944, 945. Mitchell, S. Weir, 869, 871. Mitscherlich, 348, 380, 397, 398, 630, 637. Model, 847, 855. Moellenbroeck, 116. Moerz, 865. Molasses, manufacture of, in etiology of poisoning by sulphuretted hydrogen, 493. Molitor, 127. Mooge, 877. Morbus maculosus Werlhofii, 243; bibli- ography, 243; definition of the disease, 243; eti- ology, 249; general features of the disease, 251; post-mortem appearances, 256 analysis of symp- toms, 259; nature and pathogenesis of the disease, 265; complications and sequelae, 269 ; diagnosis, 270; duration, terminations, prognosis, 275 ; treat- ment, 276. Morehouse, G. R., 869, 871. Morel, CCS, 680. Morgan, 131, 679. Morisse, 662. Morphine, Poisoning by, 841. Morris, Th., 690. Morson, 744, 795. Mortality in inhalation of chloroform, 425. Mosler, 208, 512, 532, 623. Mossop, 314. Mouldy fungi, Poisoning by, 940. Mouton, 375. Mueller, 499, 516, 536, 538, 539, 540, 541, 542, 545, 546 658. Mulder, 237, 288, 323. Munk, 325, 331, 348. Munke, 691. Muntingi. 108. Murdock, 871. Murray, 10. Murray, J., 782. 865. Muscarine, Poisoning by, 926. Muschet, W. Boyd, 854. Muscular apparatus, affections of, in haemophilia, 59; in morbus maculosus, 255 ; in poisoning by aconi- tine, 749; in poisoning by alcohol, 394 ; in poison- ing by atropine, 676 ; in poisoning by bisulphide of carbon, 481; in poisoning by calabar bean, 697; in poisoning by carbonic oxide, 468 ; in poisoning by coniine, 816; in poisoning by curarine, 832; in poisoning by lead, 567, 575, 576; in poisoning by mercury, 612 ; in poisoning by phosphorus, 636; in poisoning by picrotoxin, 811; in poisoning by potassium nitrate, 375 ; in poisoning by sausage, 543; in poisoning by veratrine, 726; in scurvy, 155, 169, 180. Miitzenbecher, 33. Nager, 338. Namias, 761. Nasse, 9, 10, 12, 16, 20, 30, 64 Nasse, O., 716, 769. 770, 835, 860. Nationality in etiology of haemophilia, 81. Nativelle, 706, 7U7. Nauseants in haemophilia, 97. Naunyn on Poisoning by Heavy Metals, 557. Nega, 818. Nelaton, 747. Neligan, 278, 815, 817. Nervous system, affections of, in haemophilia, 59; in poisoning by acetic acid, 349; in poisoning by alcohol, 394, 403, 409; in poisoning by ammonia, 357 ; in poisoning by anilin, 523; in poisoning by arsenic, 648,' 654 ; in poisoning by atropine, 6IJ6, 668, 676; in poisoning by barium compounds, 378; in poisoning by bisulphide of carbon, 479, 481; in poisoning by bromine, 318; in poisoning by carbolic acid, 530 ; in poisoning by carbonic acid, 475; in poisoning by carbonic oxide, 465, 463; in poisoning by cheese, 552; in poisoning by chloral hydrate, 448: in poisoning by chloroform, 431 ; in poisoning by cicuta virosa, 827; in poison- ing by colchicine, 736, 737 ; in poisoning by coni- ine, 816; in poisoning by copper, 591; in poison- ing by curarine, 831; in poisoning by cystisine, 823; in poisoning by digitalis, 710; in poisoning by ergot, 893, 906, 915; in poisoning by ether, 442; in poisoning by fish, 550; in poisoning by fungi, 929, 940 ; in poisoning by helleborin, 742; in poisoning by lead, 570, 581; in poisoning by mercury, 611; in poisoning by nicotine, 769; in poisoning by nitro-benzin, 517; in poisoning by opium, 849, 856: in poisoning by oxalic acid, 354 ; in poisoning by phosphorus, 633 ; in poisoning by potassium nitrate, 375; in poisoning by prussic acid, 502, 509; in poisoning by santonin, 885; in poisoning by sausage, 542; in poisoning by silver, 599; in poisoning by solanine, 691, 693; in poi- soning by sulphuretted hydrogen, 495 ; in poison- ing by sulphuric acid, 330 ; in poisoning by vera- trine, 728. Neubert, 903. Neumann, 234, 320, 321, 3S9, 413. Nickel, 894. Nicol, 314, 828. Nicotine, Poisoning by, 759. von Niemeyer, F., 161. 234. Nitre, Poisoning by, 371. Nitro-benzin, Poisoning by, 513. Nitro-glycerine, Toisoning by. 533. Nitrous oxide, Poisoning by, 454. Nivet, 724. 960 INDEX. Nobiling, 620, 623. Norris, 853. Nothnagel, 269. Novellis, 137. Nussbauni, 853. Nutrition of body, disturbances of, in scurvy, 146. Nux vomica in poisoning by aconitine, 755. Nysten, 342, 360, 456, 485. Nystroem, 533, 534. Obernier, 387. O'Brien, 691. O'Connor, 749, 750. Oertel, 358. CEsophagus, stricture of, following poisoning by caus- tic and carbonated alkalies, 369. Oettingen, 607. O'Farrell, 798. Ogle, John, 874. Ogston, 530, 532. Olivier, 855, 877. Ollivier, 208, 514, 522, 940. Onsum, 352, 376, 533, 534. Opitz, 118, 137, 145, 163, 165, 167, 172, 173, 174, 175, 176, 177, 179, 206, 236. Opium in poisoning by alcohol, 414; in poisoning by atropine, 681, 683; in poisoning by colchicine, 739; in poisoning by cystisine, 826; in poisoning by lead, 573; in poisoning by nicotine, 772; in poisoning by picrotoxin, 813; in poisoning by strychnine, 797. Opium, Poisoning by, 841. Oppolzer, 591, 592, 593, 772. O'Reilly, Th., 779, 801. Orfila, 297, 324, 338, 349. 363, 380, 485, 506, 591, 593, 594, 598, 624, 627, 661, 686, 757, 877. Osborne, 10. Oser, 768, 770, 899. Otto, 8, 19, 20, SO, 35, 45, 46, 73, 86,100, 645, 678, 687, 721, SOS. Overbeck, 602, 605, 606, 607, 614. Owsjannikoff, A., 548, 549. Ozanam, 121, 437. Paget, 361, 669, 724, 726. Pain in morbus maculosus, 252; in poisoning by acet- ic acid, 350 ; in poisoning by alkalies, caustic and carbonated, 367 ; in poisoning by alum, 381; in poisoning by ammonia, 262; in poisoning by antimony, 621 ; in poisoning by barium com- pounds, 378 ; in poisoning by calabar bean, 697 ; in poisoning by carbolic acid, 530 ; in poisoning by cheese, 552 ; in poisoning by chlorine, 289; in poisoning by cicuta virosa, 827 ; in poisoning by colchicine, 735 ; in poisoning by coniine, 815; in poisoning by ergot, 907; in poisoning by fish, 550 ; in poisoning by hydrochloric acid, 339; in poison- ing by hydrofluoric acid, 344 ; in poisoning by iodine, £00; in poisoning by lead, 566, 570, 574; in poisoning by mercury, 604, 611, 613; in poi- soning by nitro-glycerine, 534 ; in poisoning by phosphorus, 632; in poisoning by potassium ni- trate, 374; in poisoning by solanine, 691; in poi- soning by sulphuric acid, 329; in poisoning by veratrine, 724; in poisoning by zinc, 597; in scurvy, 144. Pallas, 368. Palm, 844. Pancreas, affections of, in scurvy, 172. Pander, 705. Panum, 471. Pappenheim, 632, 652, 658. Paralysis in poisoning by arsenic, 649, 654; in poison- ing by copper, 593; in poisoning by lead, 576 ; in poisoning by mercury, 613; in poisoning by sul- phuric acid, 333. Parisot, 417. Parker, 383, 387, 388. Parsons, 670, 635. Pathology. See Different Diseases. Paul, 338, 339. Paulus, 539. Pechey, 233. Peddie, 400. Pelikan, 713, 785, 833. Pellarin, 780. Pelletier, 722, 775, 779. Pelmann, 451. Pelouze, 833. Pelvet, 314, 817. Pennetier, 398. Percy, 395. Pereira, 324, 564, 763. Pericardium, affections of, in morbus maculosus, 254 ; in scurvy, 161,171, 186, 204. Perier, 708. Periosteum, affections of, in scurvy, 162, 170, 184. Peritoneum, affections of, in morbus maculosus, 254 ; in scurvy, 204. Perls, 639. Peronne, 3;3. Peroud, 662. Perrin, 383, 384, 385, 387, 395, 417, 438, 513. Personne, 446. Pettenkofer, 595. Peugnet, E., 724. Pflueger, 359, 474, 714. Pharyngeal muscles, want of reflex action in, in poi- soning by bromine, 319. Phelps, 798. Phenyl, hydrate of, Poisoning by, 524. Phipson, F. L., 886. INDEX. 961 Phosphates in poisoning by lead, 560. Phosphorus in poisoning by bisulphide of carbon, 484. Phosphorus, Poisoning by, 629. Phthisis, a complication of poisoning by arsenic, 655 ; of poisoning by lead, 567; of poisoning by mercu- ry, 614. Physostigmine, Poisoning by, 695. Picon, Lesage, 822. Picrotoxin, Poisoning by, 810. Pidduk, 778, 802. Pietrowski, 352. Pillwax, 798. Pinkham, 528. Planer, 491. Planta, 661, 744. Pleura, affections of, in morbus maculosus, 254; in poisoning by lead, 567; in scurvy, 161, 171, 186, 204. Pliny, 108. Ploegel, 663. Plum, 849. Pneumonia, a complication of poisoning by carbonic oxide, 467; of poisoning by lead, 567; of scurvy, 203. Pockels, 906. Podcopaew, 372. Podolinski, 457. Poisons, 285; Poisoning by Metalloids, 285; Poisoning by Chlo- rine, 285 ; Poisoning by Iodine, 290; Poisoning by Bromine, 3U6. Mineral Acids, 322; Poisoning by Sulphuric Acid, 322; Poisoning by Hydrochloric Acid, 337 ; Poisoning by Xitric Acid, 340 ; Poisoning by Hydrofluoric Acid, 343; Poisoning by Sulphur- ous Acid, 344. Vegetable Acids, 346 ; Poisoning by Acetic Acid, 346: Poisoning by Tartaric and Citric Acid, 351; Poisoning by Oxalic Acid, 351. Poisoning by Alkalies, Earths, and their Salts, 355; Poisoning by Ammonia and Sal Ammoniac, 355; Poisoning by Caustic and Car- bonated Alkalies, 366; Poisoning by Salts of the Alkalies and Earths, 370; Poisoning by Barium Compounds, 375; Poisoning by Alum, 379. Poisoning by Anesthetics and other Poison- ous Carbon Compounds. 382; Poisoning by Al- cohol, 382 ; Poisoning by Chloroform, 416 ; Poi- soning by Ether, 439 ; Poisoning by Chloral Hy- drate, 445; Poisoning by Amylene, 453; Poison- ing by Bichloride of Methylene, 453 ; Poisoning by Ethylidene, 454; Poisoning by Nitrotis Oxide, 454; Poisoning by Carbonic Oxide, 456; _ Poison- ing by Carbonic Acid, 472 ; Poisoning by Bisul- phide of Carbon, 477 ; Poisoning by Sulphuretted Hydrogen, 4S4 ; Poisoning by Prussic Acid and VOL. XVII.-61 Allied Substances, 498; Poisoning by Benzin, 512 ; Poisoning by JVitro-benzin, 513; Poisoning by Anilin and Anilin Dyes, 519; Poisoning by Carbonic Acid, 524; Poisoning by Nitro-Glyce- ri?ie, 533. Poisoning by Tainted Articles of Diet, 535; Sausage-Poisoning, 535 ; Poisonous Fish, 547 ; Poisonous Cheese, 551. Poisoning by the Heavy Metals, 557 ; Lead-Poi- soning, 557; bibliography, 557; detection of the compounds of lead in the animal fluids and tissues, 558; acute lead-poisoning, 558; chronic lead-poi- soning, 560; general description of chronic lead- poisoning, 565; treatment of lead-poisonir.g in general, 568; lead colic, 570 ; arthralgia satur- nina, 574; lead paralysis, 576; encephalopathia saturnina, 581; theory of the action of lead and of lead-poisoning, 583; Copper-Poisoning, 5S9; bibliography, 589; acute copper-poisoning, 59j ; chronic copper-poisoning, 592; Zinc- and Cad- mium-Poisoning, 594; bibliography, 594; acute zinc-poisoning, 595 ; chronic zinc-poisoning, 597; Silver-Poisoning, 599; bibliography, 599; acute and chronic poisoning, 599; treatment, 601 ; Mer- curial Poisoning, 601; bibliography, 601; the corrosive action of mercurial preparations upon the intestinal tract, 603; mercurial poisoning by absorption of the poison into the circulation.— Constitutional mercurial poisoning, 605; treat- ment, 617; Antimony-Poisoning, 619; bibliog- raphy, 619; general description, 621; treatment, 624; Poisoning by salts of Iron, 624; Poisoning by preparations of Manganese, 626; Poisoning by preparations of Chromium, 626; I3oisoning by compounds of Tin, 627; Poisoning by Sub- nitrate of Bismuth, 628; Poisoning by com- pounds of Gold, 628; Poisoning by Thallium, 623 : Poisoning by Osmic Acid, 629; Phosphorus- Poisonitig, 629; bibliography, 629; acute phos- phorus-poisoning, 631; treatment, 641; chronic phosphorus-poisoning. 642; Poisoning by Arsenic and Arseniuretted Hydrogen, 644; bibliography, 644; acute arsenic-poisoning, 648; chronic arsenic- poisoning, 652. Vegetable Poisons, 661; Poisoning with Atro- pine, 661; etiology, 661; nature and course of the illness, 665 ; analysis of symptoms, 671; diagnosis, 678; treatment, 680 ; changes which atropine un- dergoes in the bodies of men and animals, and tests for atropine, 686; Hyoscyamus Poisoning, 688; Solanine Poisoning, 689; symptoms and course, 690; diagnosis and prognosis, 694; treat- ment, 695; changes which solanine undergoes in the bodies of animals, and tests, 695; Poisoning by Physostigmine, 695; etiology, 606: symptoms and course, 697 ; diagnosis, prognosis, and treat- 962 INDEX. ment, 704 ; changes which physostigmine under- goes in the bodies of animals, and tests, 705; Poi- soning by Digitalis, 706 ; etiology, 708; symptoms and course, 709; diagnosis and prognosis, 718; treatment, 719; changes which digitalis under- goes in the organism, and tests, 720; Poisoning by Veratrine, 722; etiology, 723; symptoms and course, 724; diagnosis, 730 ; prognosis and treat- ment, 731; changes which veratrine undergoes in the system, 731; chemical tests, 732; Poisoning with Colchicine, 734; etiology, 734; symptoms and course, 735; diagnosis, 737; prognosis, 738; treatment, 739; changes which colchicine under- goes in the bodies of animals, 739; chemical tests, 740 ; Poisoning with nelleborin and Helleborein, 741; symptoms, 742; Poisoning with Aconitine, 744 ; etiology, 745; symptoms and course, 747 ; diagnosis, 753; prognosis, 754 ; treatment, 754; changes which aconitine undergoes in the bodies of animals, and chemical tests, 755; Poisoning with Delphinine, 757; general description, 757; Poisoning with Nicotine, 759; etiology, 760; symptoms and course, 764; diagnosis, 771; prog- nosis, 772; treatment, 772; changes which nico- tine undergoes in the organism, 773; chemical tests, 774 ; Poisoning by Strychnine, 775 ; etiolo- gy, 776; symptoms and course, 780; diagnosis, 791; prognosis, 793; treatment, 794; changes ^hich strychnine undergoes in the organism, 806; chemical tests, 807; Poisoning with Brucine, 810; Poisoning with Picrotoxin, 810 ; etiology, 810; diagnosis and prognosis, 812; treatment, 813; chemical tests and changes which the poison un- dergoes in the organism, 813; Poisoning with Coniine, S14; etiology, 814; symptoms and course, 815; diagnosis and prognosis, 819; treat- ment, 820; changes which coniine undergoes in the system, and chemical tests, 820; Poisoning by Cystisine, 821; etiology, 822; symptoms and course, 823: diagnosis, 825; prognosis and treat- ment, 826; changes which cystisine undergoes in the organism, 827; Poisoning by Cicuta Virosa, etc., 827; symptoms, 827; treatment, 828; Poi- soning by Curarine, 829; etiology, 830; symp- toms and course, 831; diagnosis, prognosis, and treatment, 837; changes which curare undergoes in the organism, 838; chemical tests, 840; Poi- soning by Opium and Morphine, 841; etiology, 844; symptoms and course in the acute form, 849; chronic poisoning, 855; diagnosis and prognosis, 864; treatment of acute poisoning, 865; of chronic poisoning, 875; changes which opium and mor- phine undergo in the organism, 877; chemical tests, 880 ; Poisoning by Santonin, 882 ; etiology, 882; symptoms and course, 883; diagnosis and prognosis, 888; treatment, 889; changes which santonin undergoes in the organism, 889; chemi- cal tests, 890; Poisoning by Ergot, 890; acute ergot-poisoning, 892; etiology, 892; symptoms, 893; diagnosis, prognosis, and treatment, 902; changes which ergot undergoes in the organism, and chemical tests, 904 ; spasmodic ergotism, 904; etiology, 904; symptoms, 9J6; diagnosis, 910; prognosis and treatment, 911; changes which ergot undergoes in the organism, 912 ; chemical tests, 913; gangrenous ergotism, 914; etiology and symptoms, 915; diagnosis, 918; prognosis and treatment, 919; Poisoning by Poisonous Fungi, 920; mushrooms, 921; symptoms, 923; diagnosis and treatment, 925; fly fungus, musca- rine. 926; etiology, 927; symptoms, 928 ; diagno- sis, 934; prognosis and treatment, 935; changes which muscarine undergoes in the organism, and tests, 937 ; amanita phalloides and agaricus bul- bosus, 938; etiology, 938; symptoms, 939; rus- sula integra and boletus luridus, 941; mouldy fxmgi, 942; dust-like fungi, 944. Pokrowsky, 458, 459, 460, 467, 626. Poljuta, 805. Pollack, 664. Pollak, 823. Polleck, 463, 493. Poma, Angelo, 868. de la Pommerais, 709, 722. Ponfick, 259. Popham, John, 822. Porta, 445. 446, 449. Potain, 365. Potash, caustic, in poisoning by atropine, 680. Potassa, salts of, in scurvy, 233. Potassium, bromide of, in poisoning by strychnine, 800. Potassium bromide, Poisoning by, 306. Potassium cyanide, Poisoning by, 507. Potassium, iodide of, in poisoning by antimony, 624; in poisoning by arsenic, 658; in poisoning by lead, 568, 579; in poisoning by mercury, 619; sulphate of, in poisoning by lead, 560. Potassium iodide, Poisoning by, 290. Potassium, Poisoning by salts of, 366. Pouchet, 937. Poupart, 123. van Praag, Leonidas, 692, 726, 728, 752, 758, 775, 818. Prevost, 932. Preyer, 4S6, 487, 500, 501, 502, 503, 504, 505, 509, 511, 682, 683, 830, 831, 836. Pringle, 163. Pritchard, 747. Proctor, 339. Prognosis. See Different Diseases. Prosper, 868. Prussak, 129. INDEX. 963 Pnchstein, 905, 906. Puczniewsky, 686. Pulse in poisoning by alcohol, 394; in poisoning by alum, 381; in poisoning by ammonia, 359, 364; in poisoning by anilin, 523; in poisoning by atro- pine, 666 ; in poisoning by bromine, 320 ; in poi- soning by calabar bean, 698 ; in poisoning by car- bonic acid, 475 ; in poisoning by carbonic oxide 458, 467; in poisoning by chloral hydrate, 450; in poisoning by chloroform, 421; in poisoning by curarine, 831 ; in poisoning by digitalis, 710 ; in poisoning by ergot, 893; in poisoning by ether, 442; in poisoning by iodine, 300 ; in poisoning by lead, 5(55, 572; in poisoning by nitro-benzin, 518; in poisoning by nitro-glycerine, 534; in poi- soning by opium, 850, 875 ; in poisoning by phos- phorus, 633; in poisoning by potassium nitrate, 374; in poisoning by prussic acid, 5C4, 510; in poisoning by sausage, 544; in poisoning by sola- nine, 691; in poisoning by strychnine, 782; in poisoning by sulphuretted hydrogen, 488, 495; in poisoning by sulphuric acid, 330; in poisoning by veratrine, 724; in scurvy, 146. Purpura Hemorrhagica. See under Morbus Maculo- sus Werlhofii. Quevenne, 706, 707, 721. Quinine in morbus maculosus, 280 ; in scurvy, 234. Rabuteau, 295, 312, 313, 387, 628. Race in etiology of haemophilia, 31, Radjewsky, 446, 448. Ranke, J., 804. Ranvier, 208. Rave, 8. Rayer, 258, 400. Raymond, 629. Reder, 245. Reese, 870. Reid, A., 777. Reimer, 451. Reinert, 26, 56, 73, 91, 98. Reitz, 358. Remak, Ernst, 577. Respiration in poisoning by aconitine, 749, 752; in poisoning by ammonia, 357, 362; in poisoning by anilin, 523; in poisoning by atropine, 668, 675 ; in poisoning by bisulphide of carbon, 478; in poi- soning by carbonic acid, 474 ; in poisoning by car- bonic oxide, 466 ; in poisoning by chloral hydrate, 448; in poisoning by chloroform, 442; in poison- ing by colchicine, 736 ; in poisoning by coniine, 816, 818 ; in poisoning by curarine, 831; in poi- soning by cystisine, 824 ; in poisoning by digita- lis, 710; in poisoning by ergot, 894, 908; in poi- soning by fish, 550 ; in poisoning by lead, 572; in poisoning by mercury, 604 ; in poisoning by nico- tine, 768; in poisoning by nitro-benzin, 518 ; in poisoning by nitro-glycerine, 534; in poisoning by opium, 850, 875 ; in poisoning by picrotoxin, 811; in poisoning by potassium nitrate, 374 ; in poison- ing by prussic acid, 502; in poisoning by santonin, 885; in poisoning by sausage, 542; in poisoning by solanine, 691; in poisoning by strychnine, 782 ; in poisoning by sulphuretted hydrogen, 494; in poisoning by sulphuric acid, 330 ; in poisoning by sulphuric ether, 442; in poisoning by veratrine, 724, 729; in scurvy, 146 ; affections of organs of, in poisoning by chlorine, 287; in poisoning by nitric acid, 343 ; in poisoning by sulphurous acid, 345 ; artificial, in poisoning by calabar bean, 704; in poisoning by carbolic acid, 532; in poisoning by carbonic oxide, 471; in poisoning by chloro- form, 438 ; in poisoning by coniine, 820 ; in poi- soning by cystisine, 826 ; in poisoning by nitro- benzin, 519; in poisoning by opium, 867; in poi- soning by potassium nitrate, 375; in poisoning by prussic acid, 511; in poisoning by santonin, 889; in poisoning by strychnine, 803 ; in poison- ing by sulphuretted hydrogen, 497. Reuling, 817. Reumont, 269. Rheumatic affections as complications of hasmophilia, 57; of morbus maculosus, 252, 264. Richardson, 424, 446, 453. Richet, 662. Richter, R., 787, 803, 893, 901. Ricord, 303, 305. Ricquet, 380, 381. Riegel, 387. Rieken, 9, 35, 36, 37, 96,100. Riekher, 809. Riemer, 601. Rienderhoff, 886, 888. Riess, 634, 636, 638, 640. Rilliet, 249. Ringer, Sidney, 667, 679. Ritter, 45, 447, 773. Roberts. 790. Rochoux, 136. Rodet, 303. Rodier, 174, 175, 176, 177. Rodolfi, Rodolfo, 800. Roeber, 682, 699, 700, 811, 812. Roerig, 758. Roethenbeck, 113. Rogers, 663. Rogow, 702. Rohlfs, 273. Ronsseus, 113. Rose, 128, 292, 296, 298, 299, 301, 302, 305, 886, 887, 889. 964 INDEX. Rosenstein, 584. Rosenthal, 292, 4S4, 485, 486, 488, 768, 769, 770, 775, S04. Ross, 824. Rossbach, 672, 674, 682, 700, 702, 703, 737, 776, 804, 871, 895, 896. Rossignol, 662. Rottwil, 123, 124. Rouge, 822. Roussin, 291, 292, 446, 506, 507, 722, 775. Roux, 10. Roux, Jules, 734, 738. Ruge, 387. de Ruiter, 672, 673, 679. Rush, 8. Russula integra, Poisoning by, 941. de Ruyter, 686. Sabadilline, Poisoning by, 733. Sabadine, Poisoning by, 733. Saccharated lime in poisoning by carbolic acid, 532. Saib-Mehmed, 314. Saikowski, 616, 623, 656. Saison, 314. Sal Ammoniac, Poisoning by, 355. Salivation in poisoning by mercury, 611. Salkowsky, 191, 199, 200, 526, 527, 528. Salter, 61. Salvatori, 407. Salzer, 817. Samson, 118, 165, 172, 186, 187, 234. Sander, 401. Sandras, 383, 564. Sandwell, 528. Sansom, 418, 426, 427, 428, 429, 430, 434, 439. Santonin, Poisoning by, 882. Sartisson, 293, 297, 304. Sastschinsky, 681, 700. Sauerkraut in scurvy, 219. Sausage, Poisoning by, 535. de Savignac, Delioux, 361. Schaefer, 43, 100, 656. Schaeffer, 666. Schaper, 655. Scheby-Buch, 247, 248, 256, 265, 269. Scheele, 507. Scheinesson, 421. Schell, H. S., 873. Schelske, 836. Schenk, 517, 518. Schiffer, 356, 475. Schlesier, 827. Schlesinger, 390, 899. Schliemann, 53. 54, 56, 61. Schloessing, 760. Schlossberger, 537, 921. Schlosser, 539. Schmid, 670. Schmidt, 33, 56, 646, 655, 6S6, 848, 883, 884, 895. Schmiedeberg, 418, 419, 440, 674, 707, 809, 926, 927, 930, 933, 936, 937, 939. Schneider, 55, 175, 176,177, 179, 602, 663, 763. SchneUer, 665, 745, 747, 748, 815, 816. Schnitzler, 591. Schoenbein, 502. Schoenbrod, 561. Schoenlein, 9, 12, 30, 47, 53, 54, 247. Schoras, 939. Schotten. 766. Schouten, 311, 314. Schoutetten, 137. von Schraud, F., 121. Schraut, 123. Schrey, 19. Schroff, 646, 664, 689, 692, 693, 737, 741, 743, 745, 746, 752, 758, 800, 814. Schroff, Jun., 682, 737, 797, 799. Schubarth, 501. Schubert, 922. Schuchard, 520, 521. Schuele, 451, 452. Schuenemann, 26, 53. Schulinus, 384, 385. Schultz, 55. Schultze, M., 887. Schultzen, 324, 634, 636, 638, 640. Schulze, 46. Schulze, O., 776. Schwartz, 468. Schwarz, 136, 205, 206. Scrinci, Anton, 905. Scurvy, 105; bibliography, 105; history, 107; general definition of the disease, 119; etiology, 120; pathology, 143; general description of the disease, 143; post-mortem appearances, 166; analysis of symptoms, 177; nature and patho- genesis of the disease, 192; complications and sequelae, 201; diagnosis, 207 ; duration, termina- tions, prognosis, 212; treatment, 216, Seasons of year in etiology of scurvy, 138. Seaton, J., 664, 678. Sedgwick, 822. Sedillot, 425. See, 894. Seidlitz, 136, 137. Selinsky, 349. Senator, 191, 248, 485, 491, 496. Senff, 468. Sennert, 116. Setschenow, 716, 812. Sewruch, 278. Sex in etiology of haemophilia, 19; of morbus maculo- INDI sus, 249 ; of scurvy, 121; influence of, upon mor- tality from chloroform, 426. Sexual functions, affections of, in poisoning by bisul- phide of carbon, 482 ; in poisoning by opium, 852. Shearman, 875. Sholes, 798. Sicard, 939. Siebenhaar, 458, 460, 466. Siebert, 773. Siegmund, 664. Siegmund, G., 717. Sieveking, 885. Simonson, 288. Simpson, 416, 512. Sinogowitz, 680 Skae. 771. Skin, affections of, in poisoning by alcohol, 394; in poisoning by ammonia, 357 ; in poisoning by anti- mony, 621; in poisoning by arsenic, 649, 651; in poisoning by atropine, 666; in poisoning by bro- mine, 320 ; in poisoning by carbolic acid, 525 ; in poisoning by carbonic oxide, 465 ; in poisoning by chloral, 451; in poisoning by copper, 593 ; in poi- soning by ergot, 906, 915; in poisoning by iodine, 304; in poisoning by lead, 565; in poisoning by mercury, 609 ; in poisoning by opium, 850, 852; in poisoning by phosphorus, 633, 635; in poison- ing by santonin, 885 ; in poisoning by silver, 600 ; in poisoning by sulphuric acid, 333; in poisoning by veratrine, 726; in scurvy, 145, 152, 167, 183. Sklarek, 656. Sleep, inability to, in poisoning by alcohol, 403. Smell, diminution of sense of, in poisoning by chlo- rine. 289. Smith, 8. Smith, A., 797. Smith, A. W., 423. Smith, H., 744. Smith, T., 744. Smith, Th., 280. Smithharst, 43. Smoler, 331. Snell, 309. Snijders, 883. Snow, 381, 430, 440, 442, 453, 454, 512. Sobernheim, 666. Sodium, chloride of, in poisoning by silver, 601; sul- phate of, in poisoning by barium compounds, 379; in poisoning by lead, 560. Sodium, Poisoning by salts of, 366. Solanine, Poisoning by, 690. Sonnenkalb, 520, 521. Sonnenschein, 637. Souchard, 360. Spahn, 55. Speech, affections of, in poisoning by alcohol. 394; in ex. 965 poisoning by alkalies, caustic and carbonated, 368; in poisoning by potassium nitrate, 375. Spence, Alexander Ingram, 789. Speneux, 939, 941. Spongier, 817. Speyer, 740. Spleen, affections of, in haemophilia, 55; in morbus maculosus, 258; in poisoning by aconitine, 753; in poisoning by digitalis, 718; in poisoning by nicotine. 771 ; in poisoning by phosphorus, 635; in poisoning by silver, 600; in scurvy, 165, 172, 188. Sproegel, 338. Spruce beer in scurvy, 223. Stadler, Th., 667. Stafford, A , 851, 867. Stannius, 711, 785. Starch in poisoning by iodine, 306. Starches, manufacture of, m etiology of poisoning by sulphuretted hydrogen, 492. Stark, 311, 319, 320, 321. Stas, 687, 774, 775, 877, 881. Stefanowitsch, 628. Steinauer, 311, 314. Steinboemer, 852. Steinmetz, 9. Steinthal, 847. Stevens, C. M., 681. Stimulants in morbus maculosus, 280 ; in poisoning by aconitine, 754 ; in poisoning by calabar bean, 704; in poisoning by cicuta virosa, 828; in poisoning by colchicine, 739; in poisoning by delphinine, 759; in poisoning by digitalis, 719; in poisoning by ergot, 903; in poisoning by nicotine, 772 ; in poisoning by opium, 866 ; in poisoning by picro- toxin, 813; in poisoning by santonin, 889; in poi- soning by veratrine, 731. Stockhausen, 564. Stoehr, 44. Stokes, 249, 633. Stokvis, 661, 668. Stomach, affections of. in poisoning by arsenic, 650; in poisoning by carbonic oxide, 470 ; in poisoning by chloroform, 436 ; in scurvy, 172, 185. Stomach-pump, use of, in poisoning by alcohol, 413; in poisoning by arsenic, 651; in poisoning by atropine. 680 ; in poisoning by calabar bean, 704; in poisoning by carbolic acid, 532: in poisoning by coniine, 820 ; in poisoning by digitalis, 719; in poisoning by lead, 560; in poisoning by mercury, 605; in poisoning by nicotine 772; in poisoning by nitro-benzin, 519; in poisoning by opium, 866, in poisoning by phosphorus, 641; in poisoning by picrotoxin, 813 ; in poisoning by strychnine, 794 Storer, 6o7. Strabo, 10S. 966 INDEX. Strauch, 291. Strecker, 746, 750. Streeter, 515. Strieker, S., 129. Stromeyer, 35, 97. Strychnine in poisoning by lead, 579. Strychnine, Poisoning by, 775. Stugocki, 767. Sugar in poisoning by copper, 592; manufacture of, in etiology of poisoning by sulphuretted hydrogen, 492. Sulphur baths in poisoning by zinc, 597. Sulphuretted hydrogen, Poisoning by, 484. Sulphuric acid, dilute, in poisoning by lead, 560. Sulphuric acid, elimination of, in form of sulphates in urine, 324. Sulphuric ether, Poisoning by, 439. Sulzmann, 844, Sulzynski, 387. Sumbul-root in poisoning by alcohol, 415. Surmay, 411. Sutton, 400. van Swieten, 125. Sydenham, 116. Symptomatology. See Different Diseases. Syphilis in etiology of scurvy, 122. Tachau, B., 682, 699. Tannin, in poisoning by aconitine, 754; in poisoning by atropine, 680; in poisoning by colchicine, 739; in poisoning by coniine, 8^0; in poisoning by del- phinine, 759; in poisoning by digitalis, 719; in poisoning by ergot, 902; in poisoning by nicotine, 772; in poisoning by opium, 866; in poisoning by strychnine, 794; in poisoning by veratrine, 731. Tanning trade in etiology of poisoning by sulphuretted hydrogen, 492. Tanquerel des Planches, 561, 563, 564, 565, 566, 567, 569. 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 586. Tardieu, 35, 255, 289, 360, £61, 367, 368, 380, 381, 436, 489, 506, 507, 520, 722. Tartar emetic in poisoning by alcohol, 415. Tartar emetic, Poisoning by, 619 Taube, Johann, 905. Taure, 720. Taylor, 298, 329, 338, 341, 342, 361, 381, 507, 510, 604, 620, 621, 622, 647, 648, 650, 664, 686, 754, 763, 771, 774, 778, 791, 845, 846, 848, 851, 853, 866, 867, 877, 878. 940. Tea in scurvy, 223. Teeth, changes in, in scurvy, 151; dangers attending extraction of, in haemophilia, 95. Teinhardt, 778. Temperament in etiology of haemophilia, 31. Temperature of body in poisoning by alcohol, 387 ; in poisoning by atropine, 675; in poisoning by car- bonic oxide, 467; in poisoning by curarine. S31; in poisoning by digitalis, 710; in poisoning by nitro-benzin, 618; in poisoning by phosphorus, 633 ; in scurvy, 166, 192. Terra ponderosa salita, Poisoning by, 375. Thai, 35, 43, 46. Thallium, Poisoning by, 628. Thiband, 796 Thielmann, 165. Thiercelin, 796. Thilesen, P., 773. Thirst in poisoning by atropine, 666. Thomas, Evan, 828. Thompson, 680. Thomson, 468. Thore, 85. Thormann, 97. Throat, affections of, in poisoning by atropine, 666, 671: in poisoning by calabar bean, 697; in poi- soning by colchicine, 735; in poisoning by coni- ine, 815; in poisoning by veratrine, 724. Thudichum, 353. Thuillier, 904. Tidy. 378. Timaeus, 370. Tinley, 824. Tissore, 666, 669. Tobacco in poisoning by strychnine, 801. Tobacco-smoking in etiology of cancer of lip, 767 ; of poisoning by nicotine, 761. Todd, 874, 875. Tomascewicz, 446. Tracheotomy in poisoning by strychnine, 805. Traneus, 41. Transfusion of blood in haemophilia, 101; in morbus maculosus, 280 ; in poisoning by opium, 867. Trapenart, 667, 669. Traube, 372, 458, 461, 471, 474, 475, 584, 587, 711, 712, 713, 715, 768. Treatment. See Different Diseases, Treulich, 516. Trier, 332. Trismus in poisoning by arsenic, 648, Truhart. 770. Tschepke, 779. Tscheschichin, 388. v. Tschudi, 810. Tuengel, 637. Turchetti, 747. Turnbull, 320, 521, 758. Turner, 337, 663, 799. Turpentine, oil of. in morbus maculosus, 278; in poi- soning by phosphorus, 641. INDEX. 967 Uhde, 37, 44, 46, 53, 54. 55. Ulcers, following poisoning by sulphuric acid, 331; in scurvy, 153. Ummethun, 526, 527, 528, 532 Ungefug. 906. Unterberger, 656. Urinary organs, affections of, in poisoning by bromine, 319 ; in poisoning by potassium nitrate, 374. Urine, changes in, in poisoning by antimony, 622; in poisoning by arsenic, 649; in poisoning by car- bolic acid, 530 ; in poisoning by curarine, 831; in poisoning by ether, 441 ; in poisoning by hydro- chloric acid, £38 ; in poisoning by nitro-benzin, 518 ; in poisoning by lead, 572, 583 ; in poisoning by phosphorus, 634 ; in poisoning by santonin, 884 ; in poisoning by silver, 60'J ; in poisoning by sulphuric acid, 324 : in scurvy, 166, 189. Urine, suppression of, in poisoning by ergot, 908: in poisoning by iodine, 300 ; in poisoning by mer- cury. 604 ; in poisoning by opium, 850. Urticaria in morbus maculosus, 269. Uslar, 808, 881. Uspensky, 708, 769, 803, 804. Uterus, action of ergot upon, 899. Vaccination, dangers attending, in haemophilia, 95. Vassal, 878. Vauquelin, 638, 741 Vella. 796. Velpeau, 298. Venesection, dangers attending, in haemophilia, 95: in treatment of haemophilia, 97. Ventilation in scurvy, 224, 228. Ventura, 224. Veratrine in poisoning by atropine, 681. Veratrine, Poisoning by, 722. Veratroidine, Poisoning by, 733. Verigo, 817. Viborg, 338, 340. Victor, 323. Vieli, 10, 12, 19, 26, 30, 35, 42, 46, 49, 53, 61, 90. 96, 97, 103. Vicrordt, 421. Vigla, 435. Vintschgau, 699. Virchow, 7, 9, 10, 30, 36, 37, 42, 47, 50, 53, 54, 55, 61, 63. 66, 67, 69, 70, 96, 198, 451, 639, 650. Viridine, Poisoning by, 733. de Vitry, Jacob, 109. Vogel, J., 63,174. Vohl, 520, 760, 761. Voisin, 316, 317, 318, 319, 320, 321, 831, 833. Voit, 607, 615, 616. Vomiting in poisoning by aconitine, 749; in poison- ing by alcohol, 394; in poisoning by alkalies, caustic and carbonated, 368; in poisoning by alum, 381; in poisoning by anilin, 523; in poi- soning by antimony, 621; in poisoning by arsenic, 648 ; in poisoning by barium compounds, 376 ; in poisoning by bisulphide of carbon, 482; in poi- soning by calabar bean, 697 ; in poisoning by car- bolic acid, 530; in poisoning by carbonic oxide, 468; in poisoning by cheese. 552; in poisoning by colchicine, 735, 737; in poisoning by cystisine, 823 ; in poisoning by digitalis, 709; in poisoning by ergot, 893, 907, 915, in poisoning by fungi, 923, 929, 940 ; in poisoning by helleborin, 742 ; in poisoning by iodine. 300; in poisoning by iron salts, 625 ; in poisoning by lead, 559, 571; in poi- soning by mercury, 604; in poisoning by nicotine, 764 ; in poisoning by nitro-benzin, 51S ; in poison- ing by nitro-glycerine, 534; in poisoning by opium, 852; in poisoning by phosphorus, 632; in poisoning by picrotoxin, 811; in poisoning by po- tassium nitrate, 374; in poisoning by prussic acid, 510; in poisoning by santonin, 885; in poi- soning by sausage, 542; in poisoning by solanine, 690 ; in poisoning by sulphuretted hydrogen, 494 ; in poisoning by sulphuric acid, 329 ; in poisoning by veratrine, 724. Vossler, 810, 813. de Vrij, 808. Vulpian, 629, 796. Wach, 378. Wachsmuth, 9. 10, 18, 20, 30, 31, 34, 36, 37, 42, 44, 64, 83, 97, 100. Wagner, E., 269. Walker. £21. Wallace, 303. Waller, Tracy E., 780. Walter, 131. Walton, 798. Walz, 706, 890. Ward, Ogier, 746, 749. Wardell, 335. Warncke, 734, 736, 738. Wartmann, 751, 752. Water for drinking in scurvy, 223. 228 ; inhalation of hot vapor of, in poisoning by chlorine, 290 ; bad drinking, in etiology of scurvy, 127. Watson, 778, 783, 790. Webb, 354. Weber, C. O., 438. Weber, O., 269. Wedemeyer, 501. Weelhouse, 822, 824. Wegener, 636, 643, 644. Weigelin, 733, 734. Weil, 716. Wells, Spencer, 884 Wenzell, 891. 968 INDEX. Werlhof, 243, 278. Wernich, 891, 896, 897, 89S, 899, 901. Weitheim, 814. Westermann, 700, 701. Westphal, 579, 587, 58S. Weyland, 727. Weyrich, 779, 784, 798. Whalley, W., 857. White, John, 782. Wierus, 113, 115, 117. Wiggers, 891. Wilkens, G. P., 778. Wilks, 413. von Willebrand, Felix, 895, 898. Williams, S. A. M„ 801. Willis, 116. Wilson, 41, 53, 54, 257. Wilson, Henry, 823. Wilson, J. G.. 667. Wiltshire, 530. Windisch, 234. Winogradoff, 715, 717. Witchead, 314, 321. With, C, 408. Witherite, Poisoning by, 375. Wittstein, 913. Woehler, 347. Wolf, 378. Wolfram, 122, 140. Wollowicz, 383, 387, 388. Wood, 320, 674, 733. Woodman, Bathurst, 684. Wordsworth, 706. Wounds in etiology of scurvy, 122. Wunderlich, 341. Wundt, 836. Wutscher, 928. Wylie, W. G., 35. Wyss, 331, 332, 63S, 640. Young, David, 696. Zaab, 86. Zalewsky, 773, 820. Zamboni, 688. Zelenski, 834. Ziemssen, 468, 471. Zimm, 530, 531, 532. Zimmerberg, 38S. Zimmermann, 270, 886. Zinc, acetate of, in poisoning by alcohol, 415 : oxide of, in poisoning by alcohol, 414. Zinc, Poisoning by, £94. Zuelzer, 944. Zuntz. 457. 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