\/\l/psy i \rKi^sy g \rK NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRAR L EZTbOTSO WIN NLM051091227 I;Mr i ^^ i ^w NATIONAL LIBRARY OF MEttlGINEO NATIONAL tl;B*«RY OF MCOICJNE NATIONAL LIBRARY OF MEDICir PEPTONISED MILK. (FAIRCHILD PROCESS.) The Ideal Food for the sick, the delicate, the con- sumptive, the habitual dyspeptic, the diabetic. Peptonised Milk is milk in which the caseine has been wholly or partially converted into peptone, the degree of this conversion to be controlled at will, as determined by the needs of the case. All the other elements of the milk, the sugar, fat and mineral salts, are already provided by nature in a condition for perfect assimilation, without digestive effort. One pint of Milk, when peptonised, contains two ounces of total dry solids—Milk Peptones, Milk Sugar, Fat and Ash. Of Beef Tea, Dr. Christison says: "He was able to obtain but a quarter ' of an ounce of solid residue in a pint." This solid residue consists of "besides the trifling amount of proteid mater- ' and of fat (which latter, in prac- 3, is guarded against with great . e), only the salts of the muscle, the matin, and allied pigments, traces ' of sugar, perhaps, some lactic acid, " and the nitrogenous extractives crea- '' tin and its congeners. As the original "half pound of muscle may contain "about forty to sixty grains of the "salts, and ten to twelve grains of the ' nitrogenous waste products, the beef " tea (half pint) certainly contained no " more."—Prof. Baumgarten. Of Beef Extract, Dr. Paw says: "There are grounds for believing that " a considerable proportion consists of "products of proteid decay, materials "in course of retrograde metamorpho- " sis, that are of no use as nutritive " agents." The well nigh superstitious ideas en- tertained by the laity of beef tea, is expressed in the allusion to the " strength" which is popularly sup- posed to be extracted in the tea; after which the beef is thrown to the dogs. The working man makes soup from a joint and consumes the " strength " and the beef both. The medical profession insist that patients shall profit by the knowledge and progress of medical science, by the use of artificially digested fresh milk, etc. The Nostrum advertisers usurp functions of the physician by prescrib- ing fictitious " foods for invalids," foods which medical science has long since condemned. PEPTONISING TUBES In boxes of 1 dozen tubes, at 50 cents retail. Each tube peptonises one pint of milk. Pamphlets and samples gratis to physicians. F&IRCHILD BROS. & FOSTER, 82 & 84 FULTON STREET, NEW YORK. "*. *, THE MODERN TREATMENT DISEASES OF THE KIDNEY, PROF. DUJARDIN-BEAUMETZ, Member of the Academy of Medicine and of the Council of Hygiene and Salubrity of the Seine; Editor of the Bulletin Ge'ne'ral de Therapeutigue, Paris, France. TRANSLATED FROM THE FIFTH FRENCH EDITION BY E. P. HURD, M. D., Neivburyport, Mass. issa GEORGE S. DAVIS. DETROIT, MICH. V, Di' *& Copyrighted by GEORGE S. DAVIS. 1888. INTRODUCTION BY THE AUTHOR. Dr Hurd has asked me for a short introduction to his translation of my lectures on the Therapeutics of Diseases of the Kidney. The importance of a knowledge of this department of in- ternal pathology and therapeutics is incalculable, and scarcely a day will pass when the physician in active practice will not have occasion to make application of some of the principles laid down in this treatise. Much has been learned these late years as to renal pathology and symptomatology. We know to-day that one of the first results of fibroid degeneration of the vascular system (a morbid change so frequent), is sclerosis of the kidney, and this alteration entails renal insufficiency. In this insufficiency, the presence of albumen in the urine plays but a secondary role, and one which cannot serve as the basis of prognosis. Far different, however, is the case with that inevitable consequence of renal failure, the retention in the blood of toxic alkaloids secreted by the economy, and it is to the accumulation of these uro-toxines that we must ascribe that odd complexus of symptoms called uraemic poisoning. Therapeutics may do much to oppose this systemic poisoning by favoring through other emunctories the elimina- tion of these toxines. I regret that the plan of my work forbade my devoting as much space as I would have liked to the consideration of this important therapeutic subject. But those readers of this work who desire more full information on the topics to which I have just alluded, would do well to read carefully VI. my lectures on " Prophylactic Hygiene," of which the advance sheets are furnished by me to my friend Dr. Hurd, and which are now in process of publication in the Therapeutic Gazette. Despite these reservations, I trust that medical practi- tioners in the United States will find in these lectures many hints that will be of value to them in their practice, and I again express my grateful acknowledgements to Dr. Hurd, who has so carefully rendered my conferences, and to Mr. George S. Davis, the publisher, for giving to these lectures so large an audience in the great American Republic. Dujardin-Beaumetz. Paris, France, Nov. io, 1888. PREFACE. In the preparation of this little volume, the translatoi acknowledges his obligations to his daughter, Dr. Kate C. Hurd, Interne of the New England Hospital, who has rendered him assistance; while for all mistakes or imperfections in the translation, he assumes responsibility. He also desires in this place to thank the author, who kindly provided him with the advance sheets of the Fifth Edition while it was going through the press, and thus enabled him to present to American readers a work which may be re- garded as fully up to the times. This same favor was extended to the translator while the preceding volume on the "Mod- ern Treatment of Diseases of the Liver " was in the course of preparation, so that both works may be considered as repre- senting the latest advances. By this, and by similar acts of kindness on other occasions, Dr. Dujardin-Beaumetz has placed both the translator and the American medical public under lasting obligations to him. Nrwburyport, Mass., Nov. ioth, 1888. TREATMENT OF DISEASES OF THE KIDNEY, CHAPTER I. THE KIDNEY FROM A THERAPEUTIC STAND- POINT. Summary.—The Anatomy of the Kidney—Renal Epithelium —Theories of the Secretion of Urine—Theories of Wit- tisch and Kiiss—Ludwig's Theory—Bowman's Theory— The Kidney as a Selecting Filter—The Urine—Composi- tion of Urine—Quantity of Urine—Solid Matters in Urine; Means of Recognizing Them—Urea—Process of Analysis for Urea—Chlorides—Method of Analysis for Phosphates—The Kidney from a Therapeutic Standpoint —The Elimination of Medicaments by the Kidneys—Im- portance of this Elimination—Rapidity of Elimination— Length of Time Occupied by this Elimination—Laws which Preside Over this Elimination—Dangers from Non-elimination—Toxic Action of Medicaments. Before entering upon the study of the therapeu- tics of renal affections, I propose, as I have done in lectures upon the other organs, to sum up as briefly as possible the anatomy and physiology of the kidney, and I shall lay especial stress upon the clinical study of the urine. I shall show you, in fact, that it is impos- sible rationally to treat diseases of the kidney without examining carefully and almost daily the modifications which take place in the urine. It is necessary for every physician to make this examination for himself, and you will see that in following certain rules, this examination is quite simple and easy. You know the anatomy of the kidneys, you know their form and situation, you know the different ele- ments which enter into their structure, and I will not dwell upon these points. Consisting essentially of the Malpighian bodies which are enveloped in the capsule of Bowman, the kidney may be considered as a mass of glomeruli, and of tubes which carry away the pro- ducts which transude through these glomeruli. The urinary conduits, you know, are of three varieties: the convoluted tubes (tubuli contorti); then tubes of smaller size called the loops of Henle, placed, so to speak, in the course of the tubuli contorti; finally, the straight, radiating, collector tubes (tubuli recti) ending in the calices of the renal pelvis. The epithelium in all of these tubes plays a con- siderable role in urinary pathogeny; it is not the same throughout the whole extent of the excretory tube. Spheroidal in the first portion of the convoluted tubes it becomes pavement in the descending branch of the loop of Henle, and finally cylindrical in the collecting- tube. Heidenham has made a complete study of the renal epithelium. He has shown, first, that the epithelium which — 3 — lines the Malpighian capsule is prolonged between all the capil- laries. This endothelium is formed of flat membrane-like cells; the epithelium of the convoluted tubes is especially re- markable for the presence of little rods crowded against each other. These rods take the direction of the long axis of the cell, that is to say are perpendicular to the axis of the canaliculus. We do not yet know the function of this epithe- lium. That of the straight portion of Henle's loop is very regu- lar, and has prominent nuclei in the descending part, but in the ascending portion we find again the epithelium with rods. The difference in the characters of these epithe- liums indicates a difference in their functions, and you will see when I come to the theories of urination, that physiologists have ascribed to these cell-elements no inconsiderable role. Prevost and Dumas in 1823, showed that the urine is separated from the blood by the kidney, and what they then demonstrated, is to-day unattack- able, despite the opposition made to these teachings by Oppler, Chrzonszezewsky, Zalesky and others. This view is based upon the experiment which con- sists, either in removal of the kidney, or in ligating the renal vessels, and we know that in these cases the urine must accumulate in the blood; this fact is more- over demonstrated to-day with all the scientific pre- cision desirable by Grehant and Pawlinof, of Moscow. But to say that the kidney only separates the materials of the urine accumulated in the blood is not enough; physiologists havevtried to go farther and ex- plain the intimate mechanism of this nitration; hence three theories have been propounded. The first is that of Wittisch and Kuss, who affirm that through the epithelial membrane covering Bow- man's capsule, not only the urine filters, but albumen as well, and that the convoluted tubes which are a continuation of Bowman's capsule have for their func- tion to absorb the albumen and allow the urine to flow off. In this event the kidney would be a veri- table dialyzing organ, since, on considering the mem- brane of Bowman as a dialyzing membrane, we find it surrounded, above as below, by an albuminous liquid. You see also the great importance of the epithe- lium lining the convoluted tubes, as it is the function of this epithelium to absorb the albumen, and accord- ing to this view, in order that the albumen shall pass out in the urine, it is enough that these epithelial elements shall be altered or be wanting. According to Ludwig's theory, the urine issues ccompletely formed from the blood plasma through Bowman's capsule, but it is very aqueous, and the epithelia of the convoluted tubes have for their function, not merely to return the albumen to the blood, but to absorb water as well, and thus concen- trate the urine. According to another theory, that of Bowman the function of the epithelium of the convoluted tubes is also very important, for, in the view of this physio- logist, water alone filters through the capsule of the glomerulus, and the epithelia of the convoluted tubes have for their office to secrete certain azotized matters — 5 — and in particular urea. This theory, which is widely different from that generally accepted, gives to the convoluted tubes a role preponderating over that of the glomerule. These views have been regarded as untenable by some, and have been adopted by others, but the ex- perimental demonstration is still wanting. But at the same time, all are agreed, physiologists and clinicians, in attaching a considerable importance to the epithel- ium of the excretory ducts of the kidneys, and in admit- ting that here, in some sort, exists the key to the normal functions of the renal organs, and to the pathological troubles of urination. This epithelium, as Farabeuf has remarked, has its moments of inactivity and ex- citation; it grows old, like the rest of the organism, and as its period of activity is increased or diminished, we find more or less marked disturbances supervening in the economy; in a word, the kidney is indeed a fil- ter, as Prevost and Dumas have said, but it is an in- telligent filter, and if you will allow the expression, it is a selecting filter, /. e. it seems to choose out certain elements from the blood to eliminate them. The importance of this function of filtration per- formed by the kidney is still further illustrated in the recent interesting researches of Gautier and Bouchard. Gautier has shown that in the normal state the animal economy is capable of producing alkaloids whose toxic properties are very great; these alkaloids (ptomaines and leucomaines) are normally eliminated by the — 6 — various secretions (sweat, saliva, and especially by the urine); if the renal secretion is below the normal, or is suspended, we can see the terrible danger to which the individual is exposed in whose blood products of extreme toxicity are accumulating. The labors of Bouchard and Charrin have given the question a further extension, and according to the results of these studies it is not the ptomaines alone which are such deadly agents. Bouchard has attained to a new conception of uraemia, according to which this is a complex kind of poisoning, in which participate all the poisonous principles introduced into, or originating in the organism. When the quantity of toxic principles generated in twenty-four hours can no longer be elim- inated in the same space of time by the kidneys, in consequence of the lessened permeability of these organs, then there is danger ahead. But Bouchard has gone even farther; he has sought to establish the coefficient of the toxicity of dif- ferent urines, and also to determine what arc the sub- stances which play the principal role. Attaching com- paratively little importance to urea, to uric acid, crea- tine, leucin, tyrosin, xanthin, etc., he has ascribed a predominant part to the coloring matters, salts of po- tassium, and various other toxic substances, and thus as I have told you, uraemia is, in his view the result of several kinds of poisons, of which the characters differ as this or that substance predominates. Bouchard has found in urine seven toxic principles I. A diuretic, urea, which is very slightly toxic, 5 or 6 grammes per kilogramme are necessary to kill a hare. 2. A narcotic, very poisonous, whose chemical composi- tion is still unknown. 3. A sialogofue which produces an abundant sialorrhcea. 4. A contracter of the pupil. £. A hypothermic ant principle (/'. e., heat-depressor). 6. An organic convulsivant. 7. A mineral convulsivant, potassium. These different poisons proceed from four sources: 1. From food. 2. From certain eminently toxic secretions, for example, saliva and bile. 3. From the disassimilation of the tissues and the waste of the organism. 4. From intestinal putrefaction produced by microbes which infest the digestive tube. To establish the coefficient of the toxicity of urines, Bouchard made use of the hare for his sub- ject, and he named the unit of toxicity necessary to kill one kilogramme of the hare's weight, urotoxia.* * If into the veins of the ear of a hare you inject twelve to fifteen cubic centimeters of normal urine, you observe my- osis, acceleration of the respiratory movements, which diminish in amplitude as sleep comes on, lowering of temperature, and finally the animal dies in convulsions. If you inject pathological urine, you see superadded a cer- tain number of new phenomena: albuminuria, haematuria, and convulsions. If after having evaporated the urine to dryness, you treat it with alcohol, and make a watery solution of the alcoholic extract, you notice that with the substances soluble in alcohol As a result of his studies, Bouchard has been able to show that normal urine is much more toxic than urine of urgemic patients, which might have been foreseen, since the renal filter in the latter instance has ceased to eliminate the poisons, which are hence retained in the blood. He has shown also by this physiological experimentation that the urine of the waking state is more toxic than the urine secreted during sleep, waste during the waking period being greater. But I cannot enlarge on this interesting subject, which has been so well set forth in Bouchard's later writings. Urine is one of the most important pro- ducts of excretion in the economy; I cannot here go into a complete physiological dissertation on this liquid, and shall have to refer you therefor to your text books. Yvon in the following table gives the composition of normal urine per litre during the 24 hours: GENERAL CHARACTERS. _ , . , j Man . .. 1400 to 1500 grammes. Quantity in 24 hrs 1 „7 » *» / t ( Woman, 1100 to 1200 " Consistence................ Fluid. Colour.................... Amber yellow or citron. there are produced somnolence, coma, diuresis, but not myosis nor hypothermia; there is also an abundant salivation. If. on the other hand, you inject the substances insoluble in alcohol, you obtain myosis, fall of the temperature, and convulsions. — 9 — GENERAL CHARACTERS—CONTINUED. Aspect.................... Transparent. Deposits.................. None or flocculent, little abun- dant. Odor...................... Sui generis. Reaction.................. Slightly acid. Density................... 1018 to 1022. Per Litre. In 24 hrs. Organic elements.......... 26 to 27 grams. 35 to 36 gr. Mineral " ........... 8.5 to 10 12 to 14 Sum of substances in solu- tion .................... 13 to 37 52 to 62 ORGANIC ELEMENTS. Urea..|Man............. i8to24gr. 25to38gr. ' Woman........... 16 to 20 20 to 22 Uric acid.................. 0.30100.40 0.50 to 0.70 Hippuric acid.............. 0.20 too 25 0.30 to 0.40 Creatin and Creatinine..... 0.40 to 0.80 0.60 to 1.20 MINERAL ELEMENTS. Hydrochloric acid!........ 4 to 5 gr. 6 to 8 gr. Chloride of sodium......... 6.6 to 8 10 to 12 Sulphuric acid............. 2 to 3 Phosphoric................ 1.66 to 2.20 Lime .................... 0.20 to 0.30 0.35100.45 Magnesia................. o.iotoo.13 0.15 to 0.20 You know that urine presents a special composi- tion, which makes this liquid, so to speak, consist of two urines; the one, solid, the most important, is com- -- IO -- posed of azotized and mineral matters; the other, liquid, is the urine containing only water.* * Different authorities give different estimates as to the proportion of solids excreted in the 24 hours. Becquerel (French) gives the estimate at 39.52 grs.; Harley (English) puts it at 53 grs ; Lehmann (German) makes it as high as 67.82 grs. Age and sex have a great influence on the solid elements of urine: thus children excrete proportionately more solid ma- terials than adults, and women less than men, as the following table from Harley shows: URINE OF 24 HOURS—AVERAGE WEIGHT 140 POUNDS, AGE 25 YEARS. MEN. WOMEN. Total amount of solids............. 53.00 grammes. 44.50 grammes. Organic substances .................. 36.00 " 31.00 " Inorganic ..... ................ . .. 16.40 " 135° " Solid material for each pound of the body weight....................... 0.37 " 0.35 " These observations were taken on English adults of both sexes, and the table comprises the mean of four analyses. According to Harley, pregnancy has a great influence on the excretion of solids, and the nearer you approach the time of delivery, the more these materials diminish. In disease, you notice also generally a diminution. Among medicines, some increase, others lessen the quantity of these substances in the urine. Among the first are opium, morphine, cicutine, hyoscy- amus, Indian hemp, citrate of iron and quinine; among the second, digitalis,atropine, colchicum Alcohol and beer, accord- ing to Bocker, diminish the solids, while Rhine wine augments them. Reptiles, and all animals deprived of a urinary bladder and having ureters opening directly into the rectum, render solid urines, and these urines only differ from liquid urines in the absence of water. — II — Urine, in the normal state, is always acid, and if it becomes neutral, it is only as Fustier has shown, be- fore a meal;* it presents also a variable color, due, you know, to a singular coloring matter, urobilin, which is derived like bilirubin, from the coloring matter of the blood corpuscles, haematin; finally it contains among its nitrogenized materials very important substances, urea f and uric acid, which are the waste products of the organic combustions of the economy. * Bence Jones has claimed that there exists a compensa- tory equilibrium between the acidity of the urine and that of the gastric juice. According to him, the urine is at its mini- mum of acidity at the time when the stomach is at its maxi- mum of acidity. Roberts has maintained that the urine becomes alkaline two or three hours after meals. Byasson affirms that the urine is least acid after the first meal, while the most acid urine is that of the night. Neubauer and Vogel have adopted Byasson's view. Georges also holds that the alkaline reaction appears two hours after the meal. Delavand affirms, on the contrary, that the urine is acid during the entire day except in the morning, when it is generally neutral or alkaline. Finally, Fustier, who has made an important study of the reaction of urine, has shown that urine is always more acii after meals, and that its maximum acidity is about four hours after dinner; urine, on the contrary, is always neutral or alkaline about eight or nine o'clock in the morning, or before the ingestion of any food. f Urea CH4 N20 was discovered in human urine by Rou- elle, in 1771, and obtained in a state of purity by Fourcroy and Vauquelin in 1779. I* is formed in the blood, eliminated by the kidneys and is found in the urine of all animals; it exists also in the amniotic fluid, the aqueous humor, vitreous humor, -- 12 -- The quantity of urine is variable, and on an average, an adult man passes daily from 1200 to 1300 grammes of urine, representing 33 grammes of urea. The Germans and the English give a somewhat higher figure, which results from the dietetic habits of these two nations, who eat and drink more than we sweat, saliva, chyle, lymph (Wlirtz), in vomited matters, in pleuritic effusions, etc. It crystallizes in the form of silky needles, or of long, flat, four sided prisms, which are color- less, odorless, of fresh and pungent savor. Soluble in water and alcohol, scarcely soluble in ether, urea melts at 1200 C. and is decomposed at 1500 setting free ammonia, and leaving a white residue of cyanuric acid. Urea combines with acids, oxides, and salts. If you add nitric acid to a concentrated solution of urea, you obtain nitrate of urea, in the form of white, lamellated crystals, sometimes in prisms, soluble in water and in alcohol. You obtain also, in a similar way, oxalate and hydrochlorate of urea. Woehler has obtained urea artificially by the union of cyanic acid and am- monia. If, in the place of ammonia, you employ the ammonia compounds, you obtain products homologous to urea, which are described under the name ot urea compounds (ethylurea, di- ethylurea, etc.). Finally, the name ureids is given to com- pounds of urea, with acid radical. The average quantity produced by a male adult who lives on mixed diet and exercises moderately, is 18 to 23 grammes of urea to the litre of urine; in women the average is 15 to 25 grammes to the litre. Harley, in his experiments, has found: QUANTITY OF UREA IN URINE OF THE TWENTY-FOUR HOURS. Boy of 18 months................ 8 to 12 grams. Girl of 18 months................ 6 to 9 " Man, 27 years.................... 25 to 35 " Woman, 27 years................. 20 to 30 " — i3 — do. But I believe, with Farabeuf, that we can lay down this law, that a man excretes by day and by kilogramme of his weight, one gramme of solid urine containing one-half gramme of urea. If I am obliged to be brief on the physical and chemical properties of the urine, as well as on the modifications which it may present, I shall, neverthe- less, be more explicit on the chemical means which enable us to analyze this secretion. Every physician ought to be competent to detect the principal elements of the urine, for without the ability to analyze or properly to test the urine, it is impossible for him ac- Nitrogenous foods augment the elimination of urea, all non-nitrogenous foods diminish it, and the experiments of Von Franque show clearly the influence of a purely animal diet: UREA IN UREA FOR EACH POUND OF KIND OF FOOD 24 HRS. PER HOUR. WEIGHT OF BODY. Gr. Gr. Gr. Animal [3^t] 9* 3-86 0.53 Mixed........ 87 1.58 0.21 Vegetable..... 28 1.08 0.15 Non azotued.. 16 0.69 0.09 Certain medicines augment the elimination of urea; such are: the alkaline chlorides, iron tonics, preparations of squill, juniper, etc. Others diminish the elimination; such are: coffee, tea, alcohol, preparations of mercury, digitalis, and valerian. Disease has a great influence on the production of urea; in febrile affections near the onset, in diabetes, you notice a marked increase; the contrary takes place in chronic diseases, cardiac affections, anaemia, cirrhosis, dropsy, cholera, scurvy, etc. — 14 ~ curately to diagnose the renal affections and prescribe a proper course of treatment. How can you determine the amount of solid ma- terials ? Do not forget that this is a very important point; the solid urine is the true urine; water is only the vehicle, and represents but a secondary element. One patient, for instance, who passes a great deal of urine, in reality passes but little, for this enormous amount represents almost exclusively water, while another patient, despite a consderable difference in the quantity of liquid excreted, really urinates sufficently, because his urine contains a large amount of solid material. To-obtain the proportion of solid materials, there are methods which are quite easy; you have only to know the density of the urine, and to arrive at this result, you require a urinometer. You may even dis- pense with a urinometer; you need only to know the weight and the volume of urine to know its density, since you know already by the laws of physics that the weight equals the volume multiplied by the density; to know this last, it suffices then, to divide the weight by the volume. The density of urine averages 1020, and when- ever it is below this .figure, the urine is said to be light, and to contain little solid material. To know exactly the quantity of solids in one litre of urine, it is suffi- cient to multiply by 2, the last two figures of the density. Thus, here is a urine marking 10.18, the — i5 — quantity of solids would be 36 grammes per litre. This figure 2, however, is not absolutely exact, and to render it such, it is necessary as Yvon has shown, to multiply not by 2, but by 2.33.* You are now able with the help of the figures I have given you to obtain with almost mathematical accuracy the weight of the solid materials voided in twenty-four hours by the patient; for this purpose, it suffices to know the density and volume of the urine. Multiply first the two last figures of the density by 2.33; multiply the result by the volume, and divide by 1000. This figure will represent exactly the solid materials contained in the quantity of urine which you are examining. After having thus pointed out the method of finding the quantity of solid urine, there is no more useful study than that of ascertaining the amount of azo'ized materials contained in the urine; these materials, in fact, indicate in a precise manner the state of the organic combustions; you know also that when they accumulate in the blood, they determine in the econ- omy a series of grave phenomena to which the atten- tion of the physician must be directed, when he is called on to treat renal affections. It is then neces- * Here is a general formula which makes known the weight of the solids in a given quantity of urine: x represents the we;ght sought; D th»- two last figures of the density of the urine; V the volume of the urine. __ D x V x 2.33 — i6 — sary that you should be able to detect easily these azotized substances, and particularly the urea which forms the far larger part. What are the methods to be employed in such cases? Three processes are in usage; that of the balance, that of precipitation by means of certain standard liquids, and, finally, that of volumetric analysis. The last, the only ready and rapid method, is the one to which you should resort. It is based upon the fact that urea, in presence of certain bodies, decomposes into nitrogen and carbonic acid, and it will be sufficient to ascertain the quantity of gas produced, to know the quantity of urea corresponding to it. Three sub- stances give rise to this decomposition; nitrous nitric acid, the hypochlorites and the hypobromites. The nitrous nitric acid (Millon's reagent) (i) has been used by Hetet, Grehant and Bouchard. It is a process which has the inconvenience of demanding either the use of the balance, or of chloroform which renders it too expensive and too slow for ordinary clinical examination. Lecomte was the first to employ the alkaline hypo- chlorites; it was an advance on the old methods, but still offered a serious inconvenience—the slowness of the operation, which demanded several hours for its production. The hypobromites were introduced simultan- eously into France by Yvon, and into Germany by Knopp and Huffner; it is the best process;-if is prompt, rapid and not costly. (2) — i? — You make use of an alkaline solution with this composition: B Bromine, 5 cubic centimeters. Strong lye (of soap makers),* 150 grammes. Distilled water, 100 grammes. This strongly alkaline solution absorbs the car- bonic acid set free in the reaction, and it is by the volume of nitrogen produced that you judge of the quantity of urea contained in the urine. To measure the quantity of nitrogen, you may employ the process of Yvon, of Esbach, or of Regnard, ingenious processes which enable us to make the analysis with sufficient rapidity. Certain tables constructed according to known laws, tables with which every clinical laboratory should be furn- ished, indicate to you when once the volume of gas is known, what is the quantity of urea contained in one litre of the urine. You see me every day employ these processes; you have noticed their ease and readiness of manage- ment, and I hope that you have derived therefrom this conviction that every physician, however little ac- customed to the manoeuvres of the laboratory, may quickly comprehend and execute these various pro- cedures. I know that there have been advanced numerous * From wood ashes. It is a strong solution of caustic potash. Tr. 3 BB — i8 — objections, that it has been said that these were but approximative processes, giving not the figure of urea merely, but that of all the azotized materials, that, moreover, these processes are incomplete. I acknowl- edge the justice of these objections from a purely chemical point of view, but from that of clinical therapeutics, the only one which we ought to take into consideration here, these procedures are excellent; they enable us to establish with sufficient exactness the quantity of of urea in the urine, and especially to know whether this quantity augments or diminishes in the same patient. We ought then to thank those who have taught us these easy methods of analysis, since they have so contributed to the study and thereby to the treatment of renal diseases. The examination for chlorides presents also a certain importance, though less than that for urea, and may render us some service. There is a pro- cess by standard solutions which is very simple and handy; it consists in precipitating the chlorides by nitrate of silver. To render this precipitation more visible, you add to the solution a little yellow chro- mate of potassium, which takes on an orange-red color when this precipitation is complete. You can, as Duhomme shows, use the ordinary gauged drop- ping tube, (3) and into two cubic centimetres of urine to be examined, you add a drop of yellow chromate of potassium; upon this mixture you let fall drop by drop a solution of silver nitrate made as follows: — 19 — B Argenti nitratis, 11.63 gr. Water, q. s., ut. ft., 100 c. c. It will be sufficient to count the drops which have been employed in order thus to bring the liquid to the orange-red, and to refer to the table constructed for the purpose, to know the quantity of chlorides contained in one litre of urine. The analysis of the phosphates is more important than that of the chlorides, but this examination (4) is more difficult. There has not yet been found a really good clinical process to determine the amount of phosphates, and their dosage remains still more in the province of the chemist than in that of the physi- cian. Such are the methods of rapid analysis of urine; these methods, you see, demand an instrumental outfit which is very simple and inexpensive; drop- ping tubes, Esbach's or Regnard's apparatus, a urin- ometer, some test papers, this is all the equipment neces- sary. As to the operative procedure, it is very simple, and it is sufficient to have practiced or to have seen practiced once or twice these analyses in order to be able to obtain for yourselves positive results. You will see, gentlemen, in the course of these lectures, how necessary, and I would even say indispensable, these studies are. Until now I have been occupied only with the urine and the examinations which enable us to detect and measure the principal materials which it contains, -- 20 — but there is another very important question which I must not omit, that is the study of the kidney con- sidered from a therapeutic point of view. When I was on the subject of the liver, I showed you that in respect to medicaments there are two points to be especially studied, the one concerning the aug- mentation of the biliary secretion and pertaining to cholagogues, the other, still less known, and relating to the elimination or fixation of medicaments introduced by the digestive tube into the hepatic gland. Similar considerations apply to the renal gland, and their study presents a great interest from a therapeutic point of view. Of all the emunctories whereby medicines are eliminated, the most important, and the one most con- stantly in exercise, is the renal, and despite numerous gaps in our knowledge, this emunctory is the one which is studied the most. To examine the medicines which pass out in the urine, to dose the quantity, to note the rapidity with which this elimination is effected, to know in what chemical state they are thus voided, this is to follow step by step the action of these medi- cines in the organism. Therefore I do not know any study more interesting, and I believe that the ques- tion which was propounded some years ago by the Medical Faculty of Heidelberg (5) deserves to be studied anew, because it is in this study, as Bouchardat has said, that we shall find the key to the pharmaco- dynamic action of medicines. -- 21 -- In order fully to state what we know respecting the elimination of medicines by the kidney, several lectures would be necessary, and I can here only trace the principal elements of this great problem of thera- peutics, a problem not yet solved, but which presents nevertheless, interesting points, and which you ought to know. When medicines are introduced into the system, whether by the skin, lungs or stomach, they enter the general circulation; then, after a time, they are eli- minated, and a large number of them pass off by the kidneys. But how various are the modes of elimina- tion of medicinal substances by the urine ! Some pass out without any appreciable alteration; such are the sulphates, chlorates, a great number of alkaloids, alcohol, etc.; others undergo profound modifications, these are chiefly the citrates, tartrates, and in gen- eral the vegetable acids and their salts, which are eliminated, as Wohler has shown, as carbonates. Certain substances undergo a more or less complete oxidation. Such are the sulphides, which pass out in the urine in the state of sulphates; there are some that combine with certain elements of urine, as salicylic acid, which Bertagnini has shown us, is eliminated in the form of salicyluric acid. Other remedies are de- composed, and while the volatile substances are eli- minated by the lungs, the fixed parts are excreted by the urine. This is what happens in the case of the terebinthinates; these substances are constituted, as -- 22 -- you know, by the union of an essence and a resin, and we see, for example, in the oleo-resin of copaiba, the volatile oil pass out by the lungs, while the copaivic acid is excreted by the kidneys and ex- ercises its medicinal properties upon the urinary pass- ages (6). Finally, other drugs, like rhubarb and senna, in being excreted with the urine, give it a special color (7). This passage through the kidneys of medicinal substances takes more or less time, and while there are certain substances which require five to eight days to be eliminated completely, like iodide of potassium, we see others which take months for their elimination, such as mercury, for instance, and this difference gives us an explanation of the dissimilar action of the medicaments. Medical writers have tried to refer to physiologi- cal laws this slowness or this activity in the elimination of medicaments by the kidneys, and Gubler has for- mulated this general rule, that medicinal substances are the better accepted by the economy, the nearer they are like the chemical principles which make part of the organism. According to this theory, substances similar to those which the humors contain are tolerated in greater proportion and are eliminated slowly, while, on the contrary, heterogeneous substances are' badly supported and rapidly eliminated. Thus it is that the salts of sodium are better tolerated than the salts of potassium, the chlorides than the bromides. - 23 — While recognizing the exactness of this law in a certain number of cases, I believe that it would be difficult in the actual state of our knowledge to gener- alize it so as to cover all medicinal substances; for we see certain substances like mercury, arsenic, etc., which have nothing like them in the economy, and which according to this rule, ought to be rapidly ex- pelled, require a long time for their elimination. However, if we cannot yet establish the rules which should govern the tolerance or intolerance of drugs by inquiring into their elimination, whether more or less promptly performed by the renal passages, we know nevertheless, an important factor in the elimi- nation of medicines : the dependence of this elimina- tion on the normal permeability of the kidneys. Already in my Diseases of the Heart * I have told you that one of the contra-indications for injections of morphine is an impermeable state of the kidneys; we have here a circumstance on which it is well that I should insist anew. For a long "time certain authorities, as Hahn, Guilbert, Rayer, Corlieu, had observed that in certain cases of Bright's disease, substances taken into the stomach which in the normal state impart a character- istic odor to the urine, such as turpentine, asparagus, no longer in such patients give rise to this odor. De Beauvais had collected many such facts in his thesis, in which he calls attention to the want of elimination of odorous substances by the urine in Bright's disease. * Diseases of the Heart, (Library Edition, Detroit, I887). — 24 — But it is to Prof. Bouchard that the honor belongs of having clearly set fort this fact that in nephritic pa- tients the elimination of medicinal substances no longer takes place by the kidneys, and hence they rapidly and in small doses determine toxic phenomena. He thus brings together and coordinates facts pre- viously scattered in medical literature, facts such as that reported by Todd, who noted poisoning in a gouty patient by a small dose of Dover's powder; such as that of Robert, who witnessed mercurial poisoning in a patient affected with Bright's disease after small doses of mercury; Keen and Dickinson have, more- over called attention to like facts. Since then, obser- vations have been sufficiently numerous to justify the 'affirmation that it is dangerous to prescribe very active medicinal substances for patients whose kid- neys are so far altered that elimination is wholly or in part arrested, and the danger is far greater when use is made of the hypodermic method. This question of permeability of the kidneys comes up anew in connection with salicylic acid, and has been one of the most serious arguments to allege against the introduction of this acid as a means of preservation of alimentary substances. By availing themselves of the anti-fermentative properties of salicylic acid, brewers and wine mer- chants may, as you know, prevent beers and wines from spoiling, but if these beverages thus sophisticated with salicylic acid may be taken without much, if any — 25 — harm by individuals whose kidneys perform their functions normally and actively, owing to the rapid elimination of this acid, it is not so with persons whose kidneys are diseased or in any way functionally inca- pacitated, in which event morbid accidents of a grave character supervene. Brouardel has shown us that, while in a young and healthy subject salicylic acid ^ appears in the urine a few minutes after the absorption of this acid, in an old person, on the contrary, elimina- tion by the urine is more tardy and does not declare itself till the next day, or even the second day after ingestion of the medicament. In the Lectures on Diseases of the Liver, I pointed out to you the clearly marked differences which exist between the action of a medicine introduced by the skin, and by the stomach. Medicines introduced sub- cutaneously, I told you, pass immediately into the circulation, and are eliminated principally by the urine, while medicines taken by the mouth pass to the liver, and may there undergo modifications more or less profound.* You at once comprehend the application of this fact to the particular case of alteration of the kidney, and you understand that every subcutaneous injection of an active principle may produce symptoms of poi- soning, even though it may have been administered in small doses. Such, gentlemen, are the principal considerations *Geo. S. Davis' Library Ed , p. 9, etc. — 26 — dependent on this great fact of the elimination of medicinal substances by the kidney; they have, you see, a capital importance; so we have been able to complete the old adage corpora non agunt nisi soluta by this: corpora non agunt nisi seer eta. What important discoveries would be made, what problems of therapeutics would be solved if physicians would take up anew, with all the scientific rigorous- ness which improvements in chemical and physiologi- cal studies permit, this question of the elimination of medicines by the urine ? Hence it is that I cannot too much call the attention of the rising generation of physicians to this fruitful field of investigation, so full of promise and success. NOTES. i. Millon's test is prepared by dissolving 125 grammes of mercury in 168 grammes nitric acid, density 144, then by dilut ng th's solution with twice its volume of water. Poured into the urine, this reagent decomposes the urea, giving rise to two volumes of carbonic acid gas and nitrogen. Into a tube with a bulb in the middle, weighed before hand, and contain- ing a solution of caustic potash, you pass these mixfd gases; the Co9 is absorbed by the potash, and its weight equals the increase of weight of the tube. Then, in multiplying the weight of the carbonic dioxide by 1 3636, you obtain the weight of the urea contained in the urine which is being tested. 2. Insteid of giving a lengthy note by the author, de- scribing Yvon's French process for the quantitative analysis of urea (a process which might not be easily made intelligible without suitable diagrams) the translator has taken the liberty of giving two peculiarly American metho. s, those of Dr. Green, and of Prof. Doremus. The communication of the latter was made to the New York County Medical Association. — 27 — EXHIBITION OF A NEW AND SIMPLE APPARATUS FOR DETER- MINING THE QUANTITY OF UREA IN THE URINE.* Dr. Charles A. Doremus, Professor Adjuvant to the Chair of Chemistry and Toxicology in Belkvue Hospital Medical College, presented a new ureometer which he had devised. It is a glass instiument consisting of a tube bent into two arms, a longer and a shorter one, at an angle of forty- five degrees to each other. The exiremiiy « f the longer arm, on which a graduated scale is marked, is closed, while that of the shorter one, which is provided with a bulb, is left open. The long arm is filled, by inclining it, wiih a hypobromite solution prepared according to the formula of Knapp, by dis- solving ioo grammes of sodium hydrate in 250 cubic centi- metres of water. By means of a nipple pipette a measured volume of the urine (1 cubic centimetre) is injected slowly up the long arm by compressing the nipple. A rapid decomposi- tion of the urea takes place, the bubbles of nitrogen rising in the long arm, while the displaced liquid flows into the bulb, which serves as a reservoir. With care the urine may be de- livered at a rate that permits the decomposition to take place without loss of gas, and the graduation on the glass indicates the weight of urea in the urine used Two forms of the ap- paratus were made, Dr. Doremus said: one graduated to real fractions of a gramme, the other to show grains of urea in the flui iounce of urine. The instruments were supplied by Messrs. Eisner and Amend, of Third Avenue and Eighteenth St., New York. Dr. A. Flint. Jr., said that he was glad to be able to make some remarks on the beautiful demonstration made by Prof. Doremus. It was a thing to rejoice in whenever any addition was made to the simple methods in our possession of obtaining important results, and he thought that no more im- portant matter could be brought to the attention of the busy practitioner than such a one for determining the quantity of urea as Prof. Doremus had just presented to the Association. If looked at from a practical point, excessive accuracy in this procedure was not a matter of importance. It was useless, and worse than useless, to attempt to secure excessive accuracy in such manipulations. The important points which the prac- titioner usually required to know in regard to the urine of his * From the Medical News, March 25, 1885. — 28 — patient were very few, and, thanks to the present achievement of Dr. Doremus, very simple means were now at his command for obtaining them all. In the first place a ready test for sugar was afforded by the two solutions of Dr. Squibb. The method was absolutely perfect, and by means of it the absence of sugar, which was always a more delicate matter to determine than its presence, could be positively demonstrated. In the second place, no better tests for the detection of albumen were required than the cold nitric acid test, conjoined with heat, if care was taken to have the urine under proper conditions when making the examination. In this connection he mentioned an interesting "case which had come under his observation as a life insurance examiner. There was some question as to whether there was albumen in the urine or not, and on the ap- plication of heat there was a slight, but distinct, precipitate. This was undoubtedly caused by phosphates, for when nitric # acid was added it cleared up; but there then followed a slight precipitate which was due to albumen. With the cold nitiic acid test there was, after the urine had been set aside for two or three minutes, the characteristic white zone between the nitric acid and the urine floating above it. In the third place, the question of the amount of urea arose. The practitioner wanted to know how much urea there was in the urine of his patient, so that he could judge whether the kidneys were doing their work properly in throwing off a sufficient quantity of ex- crementitious products. He had long felt the want of some easy way of determining this, and the apparatus which had just been exhibited seemed to him to meet the case precisely. He, therefore, regarded it as one of the most important con- tributions which had been presented to the profession on the subject. In conclusion, he said he should like to ask Dr. Doremus whether it was essential that the soda of the alkaline solution should be exactly in the proportion of six ounces to the pint of water. Dr. Doremus replied that the caustic soda solution should always be in excess. The quantity of alkali might be greater than this but it was never to be below it. The determination of the amount of urea of course is only ap- proximated by this method. — 29 — SIMPLE FORMS OF APPARATUS FOR ESTIMATING THE QUANTITY OF UREA IN THE URINE.* BY AUSTIN FLINT, JR., M.D., LL.D. At the request of Dr. William H. Greene, of Philadelphia, I have the honor to exhibit to the Association his apparatus for the estimation of urea. The request is contained in the following letter from Dr. Greene, and the description of the apparatus was sent to me by Dr. Greene, with the apparatus itself: I see that you have favorably noticed a ureometer exhibite'd by young Dr. Doremus to the New York County Medical Society on the 16th March. As you may possibly have noticed in a reclamation of priority, which 1 pub- lished in the Medical News of the 4th inst , 1 consider that Dr Doremus has acted either ignorantly or with but a slight appreciation of the ethics of scientific men in seeking to appropriate credit for an apparatus of which the only simplicity—the absence of stopcocks—is due to myself. At the same time he does not appear to comprehend the importance of corrections for temperature and pressure even in approximate measurement of gases I send you by express a ureometer, which please accept with my compliments, and compare with that of Dr. Doremus. I have made no advertisement of the instrument. My deceased friend, the late Adolph Wurtz of Paris, presented for me its description to the Academie des Sciences. Greiner and Friedrichs began manufacturing it immediately afterwards, and, at my request, sent me seven. This one, which I send you. is the third that 1 have presented, the other two having been given to personal friends. I would esteem it a favor if you would either read this note or exhibit the apparatus to the New York Couoty Medical Society. Very respectfully yours, Wm. H. Greene, 3235 Sansom Street, Philadelphia, April 18, 1885. "A Simple Apparatus for Estimating Urea. By W. H. Greene. (Fresenius, Zeitschrift fur Analyt. Chemie, xxiii. Heft ii. S. 275.) "A simple apparatus for estimating urea with sodium hypobromite, which has been suggested by W. H. Greene is intended for clinical purposes, and admits of rapid work. Its essential part is the glass vessel a (see Fig. 1), whose under * Read before the New York County Medical Association, May 18, 1885. Medical News, May 30th, 1885. — 3° — portion, holding about 60 cc, has a side-tube, while the upper cylindrical portion, of from 20-25 cc. capacity, is graduated. Fig. 1. - \ — 6 —002 — x To make the determination, a measured quantity of urine is introduced by means of the pipette whose end has been bent, into the glass vessel, which has been filled with hypobromite and placed in a saucer to catch the lev that escapes. J — 3i — " The nitrogen produced collects in the graduated cylin- der. It is advisable to choose a pipette whose fine end allows 3-4 cc. of urine to escape in a minute. "When the decomposition is complete, a bent funnel- tube is inserted in the tubulus, and this is filled with hypo- bromite to the same level as that in the graduate. The read ing of the volume of nitrogen is then made. If it is desired to do away with the funnel-tube, the entire apparatus may be sunk in water until the level of the hypobromite corresponds with that of the outside water. " Quantity of urea in a litre of urine = ________1000 v (h—h') 760 X 354-3 X a (1 -{- 0.00366 t) " v = volume of gas. " h = barometric pressure in millimetres. " ft — tension of aqueous vapor in millimetres at tempera- ture t. "a = volume of urine employer!." To enible members of the Association who were not present when the apparatus constructed by Dr. Doremus was presented, to make a comparison between the two methods, I take the liberty of exhibiting agiin Dr Doremus's process. It is proper, however, to state that Dr. Doremus makes no claim to originality, as is shown by the following extract from the Journal of the American Chemical Society, vol. vii. No. 3: " The general form of the apparatus shown in the cut (Fig 2) is not new. It was in use in Prof. Kuehne's laboratory in Heidelberg in 1871, where it was employed n the detection of fermentable sugais by introducing some yeast in the liquid, and setting the tube in a warm place. The carbon dioxide evolved collected in the long arm. "Since then it has been given in works on animal chem- istry." "The long arm of the tube is filled to a point marked = with a solution of sodium hydrate, six ounces to a pint of water, and one cc. of bromine is then added by means of the pipette. This extemporaneous mixture, for each analysis, is made in the apparatus itself, for the reason that the hypobro- m te is liable to deteriorate. Enough water is then added to fill the long arm and bend of the ureometer. One cc. of urine is then passed slowly into the apparatus by means of the pipette, and the quantity of gas liberated is read from the — 32 — scale, which gives the actual proportion of urea, without calcula- tions or the use of tables. The determination can thus be made in nearly the time that has been required for its descrip- tion. Fig 2. Each of the two forms of apparatus is designed to pre- sent a convenient and rapid application of a well-known method for the quantitative determination of urea. There seems to be no ground for controversy as regards originality or priority; and practitioners will undoubtedly select the ap- paratus which is most convenient. Dr. Doremus presented, by request, at a previous meet- ing of the Association, the form of apparatus which he uses in teaching, as possibly the simplest and most convenient for medical use. The graduation was made experimentally, at a temperature of 650 Fahr., with a uniform volume of liquid, so that, these requirements and conditions being fulfilled, the esti- mates are sufficienily close for all practical purposes, and " corrections for temperature and pressure " are unnecessary. 3. This is M. Duhomme's process for the analysis of — 33 — the chlorides of urine by the method which he has described under the name of clinical urochlorometry. As apparatus, the ordinary test tubes are all that is needed, and two droppers, the one guaged to hold 2 cub. c. m. of urine, the other one for a standard solution of silver nitrate (see text, page 19). Each drop of this solution corresponds to 1 gram of chloride of sodium to the litre. The operative procedure is as follows: You examine first the reaction of the urine by the litmus paper. With a dropping tube graduated for 1 c. m. you count the number of drops contained in 1 cu. c. m. of urine, then with the other graduated dropper you measure as nearly as possible 2 cu. c. m. which you pour into a test tube, and add one drop of a solution of chlorate of potash, then pour into this test tube drop by drop, the solution of silver nitrate, taking care to shake the tube each time that you put in one drop of the standard solution until this mixture takes on a brown color like that of coffee and milk. Now count the number of drops employed, and by referring to the following table (p. 34) you have the quantity of chlorides contained in one litre of urine. The Roman figures of the table represent the number of drops of urine contained in 1 cu. c. m. The Arabic figures apply to the number of drops of the silver nitrate solution used. When the urine contains albumen it is necessary to precipitate it before testing for the chlorides. 4. A long note by the author on the modern mode of testing phosphates by standard solutions of uranum nitrate, ferrocyanide of potassium and acetate of sodium, is omitted for want of room. The dosage of the phosphoric acid in the urine is effected by means of a definite solution of uranum nitrate, which pre- cipitates this acid as an insoluble phosphate; when all the PO3 is precipitated a drop of K2 FeCy3 solution colors the urine red. Phosphate of lime and phosphate of magnesia are sol- uble in acids, and therefore are not deposited in acid urines; they are excreted to about the extent of 1 gramme per day. When present in the urine in large quantity, they are pre- cipitated as an abundant white sediment, the urine being neu- tral or alkaline to test paper Phosphate of lime occurs as an amorphous powder, sometimes also in crystals, often forming beautiful star-shaped masses. Ammoniaco-magnesian phos- phate (triple phosphates) is one of the most common deposits; 4 BB — 34 — it is deposited from alkaline urine in colorless prismatic crys- tals of various sizes, tending to the coffin-lid shape. These crystals are soluble in acetic acid. TABLE FOR THE UROCHLORMETRIC ANALYSIS. Number o! drops of the solution Number of drops in one cubic centimeter of urine. of silver nitrate. XVIII. XIX._______XX. XXI. XXTI. 1. I. 1 I I.05 J.CO 0 95 0 91 2. 2.22 2. IO 2.00 1.00 1.82 3- 3 33 3.16 2.00 2.86 2-73 *• 4-44 4-'4 4.00 3-81 3 64 5- 5-<5 5-26 5.00 4.76 4-54 6. 6.67 6.3I 6.00 5-71 5-«5 7- 7.78 7-37 7.00 6.67 6.16 8. 8.89 8.42 8.00 7.62 7.27 9- 10.00 0-47 9.00 8-57 8.18 IO. 11.11 10 53 10 00 0 52 9.08 n. 12.22 11 58 11.00 10.48 10 00 12. '3-33 12.62 12.00 11.43 10.91 13- i4-«4 13.68 13.00 IT.38 11.82 14- IS 55 14-74 14.00 I3-33 12.73 IS. 16.66 '5-79 15 °° 14-28 13 64 16. 17-78 16.84 16 00 15.24 1457 17- 18.89 n.89 17 00 16.19 I5-41! 18. 20 00 18.95 18 00 17.04 16.36 IQ. 21.11 20.00 19 00 18 09 17.27 20 22 5>2 21 05 20 00 19 0; 18 18 Increase of the earthy phosphates is a characteristic of brain and nerve waste; it is also noticed in phthisis, rachitis and other wasting diseases. A temporary phosphuria may result from indiges-tion, or irritative affections of the bladder. 5. In 1823, the Faculty of Medicine of Heidelberg offered a prize for the best solution of the following problem: Determine what are the substances which, introduced into the organism of man or animals, by mouth or in any other way, pass out in the urine, and indicate what may be inferred from such knowledge. It was Wohler who obtained the prize Wohler operated on dogs which took, while fasting, in their menses the various substances experimented with, and lhen by frightening them, he made them urinate. Since then the process has been improved by catheterizing the dogs and Gerard has even proposed to utilize for this study birds' and — 35 — has given a very ingenious process by which the latter may be made available for these studies.(b) 6. Here are a few indications relative to the elimination of certain substances by the kidneys: Sulphate of Quinine.—The greater part of the sulphate of quinine ingested (fully one-half at least) is eliminated by the kidney. Its presence is noted in the urine thirty or lorty minutes after its ingestion (Gubler). Its elimination lasts from two to five days. Bromide of Potassium.—Bromide of potassium passes out in the urine, and every trace of this medicament disap- pears in from fifteen days to a fortnight after the administra- tion of the remedy. Iodide of Potassium also passes out in the urine, and takes from three to eight days for its elimination. Mercury takes a long time in being eliminated by the kidneys. Salicylic Acid is eliminated as salicyluric acid. Begins to be eliminated twenty five minutes after its ingestion, and lasts forty-five hours for a dose of thirty grains. Ferro-cyanide of Potassium.—Some say it is eliminated rapidly, others tardily in the urine. Chlorate of Potassium is eliminated unchanged in the urine; according to some authorities, in its totality. Salts of Lithia are eliminated in very feeble quantity in the urine Chloral,—Not eliminated as chloral in the urine, but formic acid and uro-chloralic acid have been found (Musculus, Hermg) which result from the decomposition of chloral; these acids reduce the cupro-alkaline liquids. Chloroform —Uncertain whether or no chloroform is eliminated by the urine. Some affirm it, others deny. Dru- raeau says it is eliminated unchanged by the lungs, and not at all by the kidneys. Carbolic Acid passes out in the urine, giving a quite special black coloration to this fluid. It is the same with resorcin. Fuchsine gives a red color, picric acid a yellowish color to the urine, which are all characteristic. Salts of Lead axe. eliminated by the urine, though slowly; their presence in the urine is difficult to detect by chemical reagents. (b~) Wohler, Recherches sur le passage des substances me'dicamen- teuses dans les urines (Zeitschnft fur Physiologic t. ier, 1824), et traduc- tion 0°urnal des progres des sciences, t. Ier, p. 45,1827).- Gerard, De la duree de 1'elimination des medicaments par les urines. - 36 - y. According to Gubler, senna and rhubarb give to urine a special coloration, making it resemble jaundiced urine; liquor potassse, however, add«td to it brings out a characteristic purple color. This reaction is due to the chrysophanic acid in the rhubarb and senna. This purple color is still more conspicu- ous when ammonia is used instead of potash. 8. These are Beauvais' conclusions: l. Failure in the elimination of medicinal substances by the urine is an exclusive pathognomonic sign of Bright's disease; 2. This sien gives due value and importance to the symptom albuminuria, and indicates the degree and nature of the corresponding anatomical lesion; 3. In absence of albuminuria the capital symptom, or of the characteristic dropsy, the absolute, incurable suppression of the passage of odors in the urine, imposes at once the diag- nosis, prognosis and treatment. However, this sign has not, according to Chauve, the value which Beauvais attributes to it. Save in cases where the complete structural alteration of the kidneys absolutely prevents the passage of odorous substances, there are very many instances where the impermeability is not complete and the elimination of odorous substances is permitted, despite en- ough renal degeneration to cause uraemic symptoms. Strauss has observed cases of this kind. 9. The modifications which characterize the elimination of medicines in renal diseases have been known for a longtime. Hahn, Rayer, Corlieu, have reported cases of impermeability of the kidney to odors (turpentine, asparagus) in albuminuria; and Beauvais, who had witnessed like facts, has even drawn the conclusion that the failure to eliminate substances by the urine is an exclusive, pathognomonic sign of Bright's disease, and may be indicative of the degree and nature of the anatomi- cal lesion. He goes even farther, and says that in the absence of albuminuria, the capital symptom, or of the characteristic dropsy, the absolute and incurable suppression of the passage of odors in the urine forces upon us at once the diagnosis prognosis and the treatment. English and French physicians have reported observations which show the intolerance of opium in certain forms of Bright's disease. Todd, Dickenson Cornil, and Charcot have related facts that are quite con- vincing. But it is Bouchard especially who has called attention to — 37 — the danger which may follow the administration of active drugs where renal lesions exist. In 1873, he published two observations of mercurial poisoning, resulting in death to two patients, the one suffer- ing from interstitial nephritis, the other from parenchymatous nephritis, and who had taken but small doses of this medica- ment. From such facts and others like them, Bouchard has drawn the conclusion that "diseases of the kidney render toxic, active medicines administered even in small doses." This conclusion seems, moreover, to be in accord with physio- logical experiments. Claude Bernard, in fact, has shown that in a curarized animal if a double nephrectomy be performed, the elimination of poison no longer taking place the animal succumbs rapidly, even though artificial respiration be kept up. Chauvet, a pupil of Bouchard, has gathered together these facts, and has undertaken researches concerning the elimination of certain medicinal substances by the kidneys; he has arrived at the same conclusions as the physician of Bicetre. Chauvet studied quinia sulphate, potassium bromide, iodide of potassium, mercury, salicylic acid, and reports a very interesting observation, especially from a medico-legal point of view, published by Dr. W. W. Keen, of Philadelphia. It relates to a man of between forty-five and fifty years of age to whom a prostitute had given opium in order to put him to sleep, and then to rob him. Falling rapidly into a comatose state, the man died 24 hours after, and the autopsy showed the existence of chronic interstitial nephritis at an ad- vanced stage. Chauvet has remarked that sulphate of quinine is elimin- ated much more slowly by diseased than by healthy kidneys, and in cases where he has been able to compute the amount of the alkaloid recovered each day of the elimination, he has always noted a quantity quite inferior to the normal. As to bromide and iodide of potassium, the elimination is also longer and more difficult. As for mercury, he recalls two of Bouchard's observations, and shows the disastrous effects of even small doses of tlrs drug. In eight patients treated by salicylic acid, the elimination was very much pro- longed; moreover, in two there was a very manifest weak- ness and languor, and in one who took only four grammes of salicylate of sodium, the toxic phenomena were a long time in disappearing. CHAPTER II. DIURETICS. Summary. —Diuretic Medicaments—Classification of Diuretics —The Kidney as a Dialyzing Organ—Tensor Diuretics— Cardiac Diuretics—Vascular Diuretirs—Mixed Diuretics —Water as a Diuretic—Dialyzing Diuretics—Advantages arid Evils of Irritant Diuretics—Anuric Medicaments— Dry Diet—Sudorifics—Opium—Valerian—Water Charged with Oxygen. Diuretics constitute a very important group in therapeutics. The. number of these substances is large, and systematic writers have endeavored to ar- range them in distinct classes, taking for the basis of their division the therapeutical action of these medi- caments. I intend in my turn to give you the classifi- cation that seems to me most logical.* * Forbes Roylle proposes the following classification of diuretics: i. Medicines acting primarily on the stomach and diges- tive system, and secondarily on the urinary organs. 2. Medicines which act primarily on the absorbents, and secondarily on the kidneys. 3. Medicines which act primarily on the urinary organs. 4. Stimulant diuretics. Wood's division is as follows: 1. Hydrogogue diuretics (squills, digitalis, broom-top, etc.) 2. Refrigerant diuretics, constituted by the entire series of neutral salts. — 39 — Of all the theories proposed to explain urination, that of Kiiss and Wittisch best accommodates itself to a physiological division of diuretics. In the foregoing chapter, I showed you that these physiologists hold that Bowman's capsule niters not only urine, but also 3. Stimulant diuretics, such as buchu, pareira brava, uva ursi, juniper, the balsams, canthaiides. Fonssagrives gives the following classification: 1. Aqueous diuretics (water and milk). - 2. Stimulant diuretics (tea, coffee, alcohol, essences, and balsams). 3. Acid diuretics. 4. Saline diuretics (acetate and nitrate of potash, and neutral salts). 5. Drastic diuretics. 6. Specific diuretics (digitalis, squills, cantharides, urea, jaborandi). • Gubler arranges diuretics into three classes: 1. Such as irritate the renal parenchyma, like nitrate of potash and urea, which 'deserve a place among the most useful of this class. 2. Tensor diuretics, i. e., such as modify the circulation by increasing the active and not the passive tension, the latter being unfavorable to diuresis. 3. Diuretics which excite the nerves of the kidney and provoke it to action; their action is similar to that of siala- gogues. These diuretics are then stimulants of the nervous system of the kidney. Prof. See divides diuretics into two groups: 1. Medicines that augment the energy of the heart and bloodvessels and thus raise the blood-pressure in the kidneys (digitalis); 2. Medicines which act by dialysis (nitrate of potash, etc.). — 4° — albumen, and in such a manner that the kidney may be considered not merely as a filter, or even as a selecting filter, but as a real dialyzing organ, since we may regard Bowman's membrane as a dialyzing mem- brane, having above and below it an albuminous liquid. Laure, of Lyons, ranges diuretics in the following order: r. Vaso-motor diuretics, such as digitalis, squills, bro- mide of potassium, ergot, tannin and plants which contain it. 2. Aqueous diuretics; plain water, mineral water, milk. 3. Neutral salts: nitrates of potassa and soda, and plants which contain them; chlorates of potassa and soda, etc. 4. The cyanides (cyanide of potassium, cherry laurel water, spiraea ulmaria, etc.) 5. Acid diuretics (sulphuric, nitric, and citric lemon- ades, vinegar and water, etc.). 6. Balsamics, such as copaiba, cubebs, turpentine, benzoic acid and plants containing it. 7. Certain excitants, which are capable, nevertheless, of retarding the movement of denutrition, such as alcohol, the effervescent wines, beer, koumys, tea and coffee. 8. Jaborandi. 9. Peroxide of nitrogen under the form of oxyazotic water. These are the conclusions at which this writer has ar- rived: 1. The diuretic medication, one of the most precious re- sources of therapeutics, responds to the following indications: a. To maintain the action of the kidney. b. To evacuate effused liquids. c. To allay irritation of the genito-urinary organs. d. To modify the urinary excretion by opposing the ex- — 41 — The kidney, then, as a dialyzing organ, must come under all the laws which Graham has indicated, and which govern the phenomena of dialysis. You all know in what dialysis consists, and what curious results have been obtained by these new cessive production of uric acid and of phosphates, and thus to prevent the formation of gravel and calculi. e. To establish a derivation by the renal emunctory. /. To aid the elimination of toxic principles peculiar to or foreign to the organism. 2. It is difficult to demonstrate that certain diuretics act either by virtue of their dialytic power, or by their influence on the blood pressure. 3. If, however, this influence does exis't, everything leads to the belief that the diuretics owe more especially their properties to an elective and thus far inexplicable action on the secreting elements of the kidney. 4. Apart, from water, squills, digitalis, ergot, a great number of diuretics are unreliable in their action, and most owe in large part their virtues to the water which is their vehicle. 5. Under the influence of alterations of the kidney which ordinarily retard elimination, digitalis becomes rapidly toxic, even in feeble doses. This is why this medicine ought to be given with great reserve in dropsies of renal origin.* * Darroze, These de Paris, 1871. Verdun, A Study of Diuresis and Diuretics. These de Paris, 1872. Wood, Therapeutics and Materia Medica, Philadelphia, 1874. Fonssagrives, Treatise on Applied Thera- peutics, Montpellier, 1878. Gubler, Soc. de Therapeutique, 1878. G. See, An Attempt at a Physiological Classification of Medicines (Bull, de Thdrap., 1878, txciv). Laure, On Diuretics (These de Agregation, 1878, Paris). — 42 — methods of research. You are acquainted with the phenomenon of the passage through an animal or vegetable membrane placed between two liquids of different composition, of the elements of one of the liquids towards the other. Now examine what takes place in the glomerule of Malpighi and in the upper portion of Henle's tubes, which before joining the straight tubes, inosculate around the glomerule. You see a membrane, Bowman's capsule, which separates two liquids; the one contained in the capillary plexus of the glomerulus, is the blood charged with excre- mentitious products; the other, in the tube of Henle, is the albuminous serum of the blood. It is through this membrane, between these two liquids of different composition, that constant exchanges take place, en- abling the components of the urine to pass into the extremities of the renal tube which conducts them out of the organism. This comparison of the kidney with a dialyzing apparatus we may pursue farther, and show that the laws which govern dialysis govern also the functions of urination. What, in fact, do these labors teach us ? This, namely, that we may influence dialysis, either by augmenting the pressure of one of the liquids, or by modifying, either the liquid itself, or the dialyzing membrane.* * When two liquids of different chemical composition are separated only ,by a membrane, or even by a septum of baked clay or very thin plates of slate, the phenomenon of — 43 — Now, in applying these three conditions to the study of medicaments designed to augment urination, we shall see that such medicines can be ranged in the four following classes: In the first class are placed medicaments which modify the blood pressure, either by energizing the cardiac systole, or by acting on the muscular element of the circulatory system. To this first group are assigned all the diuretics osmosis is produced i. e. there is reciprocal transmission of the two liquids through the diaphragm which separaies them. It was on this principle that Dubrunfaut founded his process of purification of'saccharine liquids, and in 1854 he made a communication to the Academy of Sciences upon this method of analysis by osmosis. Graham, who has given great study to this question, ap- plies to this method the name of dialysis. Dialysis consists, in fact, in the separation of substances in solution by diffusion through a septum or diaphragm of colloid matter. The instrument which serves for these experiments, and to which the discoverer has given the name dialyzer, is only a modified endosmometer. Graham prefers as a dialytic membrane, vegetable parch- ment or parchment paper, which is prepared by soaking papier Joseph a few seconds in sulphuric acid or in a solution of the chloride of zinc, and then washing it in water. This paper is applied wet to a rim of thin wood or gutta percha, 5 cm. deep and 20 or 25 cm in diameter, so as to form a sort of sieve; the edges of the disc of paper, whose diameter must be greater than that of the circular rim, are covered over the latter and fixed by a stout string. In order to prevent the diaphragm from being porous, you — 44 — already studied under the name of heart tonics, which, while augmenting the contractile power of the cardiac muscle, increase the urinary functions. Gubler gave to this group the name of tensor-diuretics. It in- cludes two varieties of medicaments, one variety, as digitalis, convallaria, caffeine, act directly on the car- cover it with a layer of albuminous liquid, which is then coagulated by heat. The liquids with which you are to operate are poured into this species of sieve, so as to form, as far as possible, a layer of only 12 millimeters in thickness. The dialyzer is finally made to float in a large vessel con- taining water enough so that the diffusion may go on through the parchment paper. At the end of 24 to 48 hours the crystal- loids are completely separated from the other matters with which they were blended. Experimenting upon urine, Graham has seen a pint of urine submitted for 24 hours to the process of dialysis, abandon all its crystalloids to the water outside, and he has seen this latter when evaporated by a sea-bath, deposit a white saline mass from which urea could be extracted by alcohol in such a state of purity, that crystalline tufts were obtained by evaporat- ing this alcohol. Graham designates under the name of crystalloids those substances which dialyze, i. e., have a strong property of dif- fusion; others, such as dextrine, starch, gums, caramel, al- bumen, tannin, and in general, all bodies of gelatinous consis- tency, and destitute of the property of crystallisation, have a very feeble power of diffusion, and have received the name colloids. But notice that, if these last substances are incapable of diffusion they allow themselves to be easily traversed by water and crystalloids. — 45 — diac fibre; others, as strychnine, ergot of rye, etc., have a special elective action upon the muscular coat of the arterial system. There has been much discussion respecting the value of these tensor diuretics; some have denied them the property of raising arterial tension, others have insisted upon this property. These contradictions, gentlemen, depend on the fact that the different ex- perimenters did not put themselves in the same con- ditions of experimentation. In fact, in the physiologi- cal state, the diuretics of this group have little or no influence; let a healthy man take digitalis, it will diminish considerably the number of his cardiac pulsa- tions, but it will augment very feebly the quantity of his urine. But, on the contrary, where there is anuria resulting from a mitral affection, you will see produced under the influence of diuretics, an excessive di- uresis; the patient will pass quarts of urine, and all the serosity accumulated in the cellular tissue and in the serous cavities will flow off by the kidneys. In the second or mixed class you will range the medicaments which produce diuresis by augmenting the pressure and modifying the liquids. This is the case with water, which Bouchardat re- gards as the best diuretic. Water introduced into the economy in great quantity augments the mass of the blood and hence the blood-pressure, while at the same time modifying its composition. Certainly, the greater part of the ptisans called — 46 — diuretic, and most of the mineral waters regarded as such, act more by the quantity of water than by the saline substances which they contain.* We may affirm that this second class of diuretics is the only class of medicaments which are truly diu- retic in the physiological state. Water taken in great abundance augments the quantity of urine, and in pathological states we always see polydypsia and poly- uria go together. So, while the medicines of the first group render as great service whenever in passive congestions of the kidney we wish to restore the flow of *If nearly all the diuretic plants act principally through the water which serves as the vehicle of their administration (infusions, decoctions, ptisans), some of them, however, owe their action in all probability to the principles which they con- tain, such as salts, essential oils, resins. The following are examples: Parietaria Officinalis.—Has sulphur and nitre. The infusion is the preferable form; 10 grammes of the leaves to a quart of water. Juniperus Communis.—Essential oil, salts of lime and potassium. Off prep —Infusion, oil. tincture. Sambucus Niger.—Salts of potassa and lime, resin, and volatile oil. An infusion of the inner bark, § ss to the Oil. (Aquae Sambuci, U. S. P.) Lappa Minor.—(Burdock). Nitrate of potash. A de coction of the root or of the seeds; (two ounces of the bruised root boiled down in Oiii of water to Oii and strained; dose, Oj, in divided doses during the day). Arbutus Uva Ursi.—Arbutin, gallic acid, resin. Off. prep.—Decoction, fluid extract, infusion, — 47 — urine, the diuretics of the second group ought to be employed when we desire to flush out the kidney and energize its functions, or, still further, when we wish to favor the elimination of toxic substances accumu- lated in the economy. In the previous lecture, I showed you that the renal emunctory, from the point of view of the action of medicines, is the most active channel of elimina- tion. I may supplement this statement by saying that it is also by this channel that man in the physiological and pathological state eliminates not only leucomai'nes Fceniculum (Fennel)—Essential oil; decoction: one ounce of the seeds to a quart of water. Apium Graveolens (Celery). — Nitrate of potash, mannite, etc. Infusion, one ounce to the quart. Asparagus Officinalis (Asparagus) —Acetate of pot- ash, phosphate of lime, mannite, asparagine. Decoction of the root, § ss dose. Scoparius (Broomtop)—Scoparin and spartein, the one diuretic, the other narcotic. Off. prep.—Decoction and succus. Iris fcetidissima (stinking orris).—Volatile oil and resinous matter. Infusion in two or three drachm doses. Centauria Calcitrapa.—Acetate of potash, chlorides and sulphates of potash, lime; the powdered leaves are given in white wine. Triticum Repens (dog grass).—Gum, triticine, silicate of potash, etc. A strong decoction is used. Scilla Maritima (Squills).—Scillitin, resin, citrate, tar- trate and phosphates of lime. Off. prep.—Acetum sciliae; pil. ipecac cum scilla; pilulae scillae co.; syrup, scillae; tinctura scillae. — 48 — and ptomaines, which, as we have seen, are constantly formed in the economy, but also the micro-organisms that develop there, and Bouchard under the names of infectious nephritis and microbic nephritis, has par- ticularly insisted on these points. You understand the interest that there is, in connection with all these infectious diseases, in favoring this elimination, and this indication is fully met by diuretics of this Stigmata of Maize (Corn Silk).—A new diuretic that has come much into use. Has mannite. Infusion and fluid extract. Spiraea Ulmaria (Queen of the Meadow).—Tannin, essential oil. Given in infusion or decoction of leaves, stem or root. Petroselinum (parsley).—Volatile oil, apiol, essential oil. Diuretic in strong infusion, Cerisier (Cerasus Caproniana).—The stones of the cherries are used; these contain tannin. Given in decoction. Borrago Officinalis (Borage).—Nitrate and acetate of potassium, salts of lime. An infusion of the leaves and flowers is given for diuretic effect. Gaultheria Procumbens.—Essential oil. Is given in infusion. Pyrola Umbellata.—Resin, tannin, gallic acid, essential oil. Off. prep.—Decoctum chimaphilae. Pareira brava.—Resin and nitrate of potassium. The decoction is principally used for diuretic purposes. The alkaline mineral waters are all more or less diuretic, both from their water and their alkaline ingredients, e.g., Con- trexville, Vittel, Evian, Vichy, Pougues, in Europe, Poland, Saratoga, Lisbon, Clysmic, Bethesda, Buffalo-lithia, etc., in United States. — 49 — second class, and in particular by milk, that admirable medicament, which, while nourishing the patient, promotes in a marked degree the functions of urina- tion. To the third class belong the medicaments de- scribed under the name of dialyzers. They produce their action by modifying the blood, and by introduc- ing into it saline elements. Thus, nitrate of potas- sium, nitrate of sodium, acetate of sodium and potas- sium, act as diuretics, and because certain plants, as Chatin has shown, contain these different salts (parie- tary, for instance), they have been found to have marked effects on the renal functions.* The dialyzing medicines which constitute this group have over the preceding a real disadvantage, in that by their presence they irritate the renal paren- * The researches of Chatin have shown that the presence of nitrates in plants is a general fact, but variable according to soil, kind of leaves, kind of species. Besides the paster (Isatis tinctora), the stinking goose foot (Chenopodium Vulvaria) the borage, the nettles, the beet, pari- etary, etc., Chatin has observed that all the plants which be- long directly, or by near relationship, to the category of mural plants are rich in nitrates. Plants growing on rocky soil, es- pecially those of the porous limestone rocks, abound in nitrates, like mural plants. Other species, such as grow in meadows (ulmaria), shady places, (belladonna), and fields (fumetary knot grass), are rich in nitrates like those of the walls and rocks. Corn, oats, barley, rye, are poor in nitrates. It is not so however with buckwheat and maize. Among the most nitriferous families, we find the Cheno- 5 BB — 5o — chyma, and often provoke too much irritation in the digestive tube. This it is that happens whenever the dose of nitre is carried too far. So, for my part, I make but little use of these diuretics, much preferring those of the preceding group. The fourth class includes those medicaments which have the property of modifying the dialyzing membrane. These are substances which actively con- gest the kidney. Thus it is that resins and balsams enter into the class of diuretics, but the disadvantages which I mentioned in connection with the preceding group are here still more pronounced; the urine is in- creased, to be sure, but it is also profoundly modified. Hence the balsams and resins render us greater ser- vice in diseases of the urinary passages by lessening the effects of putridity of the urine, than by any real diuretic action. Such, rapidly summarized, is the classification podiaceae, Amarantaceae, Caryophyllaceae, Polygonaceae, Sola- naceae, Papaveraceae, Fumariaceae. The dioctyledons contain generally more nitriferous plants than the monocotyledons, and among the acotyledons, the mosses hold the chief place, the lichens, mushrooms and algae the last. Among cultivated plants, such as exhaust the soil (as the gramineae), are altogether poorer in nitrates than those that improve the soil, such as the leguminosas. The nitrates accumulate in the woody parts, sometimes also in the roots; they are least abundant about the time of maturation of the fruits. — 5i — which seems to me the best of the great group of diuretic medicines. Alongside of diuretics, we should place, by way of contrast, the anuretic medicaments, for if in certain cases (ordinarily the most numerous) the chief indica- tion to fulfil is to augment the quantity of urine, there are other cases, on the contrary, where it is the oppo- site indication which should be met, as in that badly defined disease which is described under the name of diabetes insipidus or simple polyuria. Unfortunately here we lack very precise indica- tions, and it is by a rather tortuous way that we attain our end. Thus, it is by reducing the amount of liquids ingested that we may to a considerable extent diminish the quantity of urine secreted, and by pro- moting the functions of the skin and favoring profuse sweats, we also diminish the sum total of the urine. Thus, pilocarpine in subcutaneous injections, and cer- tain phenols such as antipyrine, may lessen the amount of urine by quite a considerable degree. Lastly, certain substances, such as opium, and especi- ally morphine, by acting on the capillaries of the kidney, diminish diuresis in notable proportions. Finally, there is a group of medicinal substances of which the anuretic action is quite manifest, such as tincture of valerian, vaunted by Trousseau in polyuria. Water charged with oxygen (oxygenated water), Ozanan says, produces the same effect, ■ with- out our being able to understand the intimate cause — 52 — of this action, and it would be of interest to arrange in a line parallel with the different groups of diuretics, a like group of medicinal substances called anuretics, and I call your attention to this interesting subject. Such are the brief considerations which I wished to present to you relative to the subject of diuretic medicaments, and I will enter at once upon the main part of my subject by setting forth the treatment of urinary lithiasis. This shall be the subject of my next lecture. CHAPTER III. TREATMENT OF URINARY LITHIASIS. Summary:—Urinary Lithiasis—Acid Lithiasis—Alkaline Lith- iasis—Uric Gravel—Its Characters—Oxalic Gravel— Phosphatic Gravel—Treatment of Urinary Lithiasis— Etiology of Uric Gravel—Uric Diathesis—Alimentary Causes—Pathogeny of Uric Gravel—Therapeutic Indica- tions—Alkalies, Indications and Doses—Choice of Alkalies—Salts of Potassa—of Lithia—of Soda—Hygi- enic Treatment—Influence of Diet—Treatment of Oxalic Gravel—Causes of Oxalic Gravel—Therapeutic Indica- tions—Ammoniacal Gravel, Causes, Therapeutic Indica- tions. Gentlemen:—Urinary lithiasis is a common dis- order which you will often be called upon to treat. I intend to give particular attention to this subject, from the fact that we may, in the great majority of cases, by an appropriate hygienic and medicinal treat- ment, cause this lithiasis to disappear. 1 shall divide my lecture into two parts: In the first I shall take up the treatment of the lithiasis itself, and in the second, that of the accidents of which it may be the cause. In considering the treatmeut of urinary lithiasis, I shall confine myself to the subject of what is called supra vesical lithiasis; in a word, I shall not touch up- on stone in the bladder, an affection which claims a surgical treatment quite outside of the plan of these lectures. It should be understood, also, that under — 54 — the name lithiasis, I do not comprehend the solid deposits of the urine, and what Bouchardat calls urine dust. These deposits of solid particles and this "urine dust" are only produced after cooling of the urine, while, on the contrary/in urinary lithiasis, the solid particles are formed in some part of the urinary passages before the urine is voided. You know that authorities have divided lithiasis into different groups, according to the size of the solid particles contained in the urine, and that they have described as sand, gravel, and calculi, deposits whose component parts are of varying dimensions. This classification presents little interest from a therapeutic point of view; it is riot so, however, with the division which is based on the nature of the lithiasis. You will see, in fact, that the cure of the affection depends on the exact knowledge of the nature of the calculi, and in the adaptation of a special treatment to each of those varieties. So, whenever a patient comes under your care for renal lithiasis, you ought, first of all, to ascertain the chemical nature of this lithiasis, and to attain this end, you will have recourse to chem- ical tests and to microscopic examinations; these tests are very simple, and the microscopic examination easy. The history of urinary concretions goes back to the most remote antiquity, but among the ancients stone in the blad- der was much better known than renal lithiasis. Hippocrates speaks of the action of calcareous waters, and of stagnation of the urine as causes of gravel. — 55 — Galen carefully describes renal lithiasis; he speaks of nephritic colic, and counsels two kinds of treatment; abund- ant ingestion of water for lithiasis, and blood lettings for nephritic colic. Aretasus, who also gives a complete description of lithia- sis, insists that if medicines may have a solvent action on the small concretions, they remain without any effect on vesi- cal calculi of considerable volume. Sydenham, Baglivi, Morgagni, Hoffmann, Boerhaave and Van Swieten describe urinary lithiasis and vaunt the utility of alkalies. In 1776 began the chemical studies on lithiasis. Scheele discovered lithic (uric) acid in calculi. Bergmann found phos- phate of lime. Wollaston completed the^e researches by find- ing cystic-oxide, and the ammoniaco-magncian-phosphate. Marcet discovered calculi of xanthine. Lastly, in 1819, Brug- natelli summed up all these facts in a remarkable treatise. The modern epoch begins with the labors of Proust, Magendie, and the remarkable treatises of Civiale in 1838, and of Rayer in 1841. When we take a general view of the nature of calculi, we see that some of them form in acid urine, others in alkaline; hence the names acid lithiasis and alkaline lithiasis. In both cases, the lithiasis may be constituted by products found normally in the urine, or by substances introduced there accidentally, or which have developed pathologically; hence the subdivision of lithiasis into normal and abnormal. In acid urine, we have as normal lithiasis, uric gravel, and as abnormal lithiasis, oxalic gravel. In alkaline urine, we find as normal lithiasis, calcareous gravel, and as abnormal, ammoniacal gravel. - 56 - Let us then begin the study of urine containing calculi by testing the reaction of this liquid, and by the sole fact of the latter being alkaline or acid, we shall be able to make a first distinction. Is the urine acid ? You will have to examine if it be a case of uric or oxalic gravel, and here the microscope and the chemical reactions will enable you easily to arrive at the diagnosis. Uric gravel, which is much the most common kind, is constituted by a reddish brick-dust sediment) such as you will often find in the urine of individuals who have passed their fortieth year, and which is very often seen in the urine of the arthritic. Examine this brick-dust precipitate under the microscope, and it will appear to you under the form of crystals resem- bling a whet-stone, of a characteristic reddish-yellow or orange tint. In other cases, the forms are more variable, and you have before you odd crystals, lance-shaped or in the form of rosettes, daggers, halberts, canine teeth, nails or spines. The figures which I here present (Figs, i and 2) give you a very clear and characteristic representation of these crystals. As for their chemical reaction, it suffices to touch these calculi with a little nitric acid and to add a drop of ammonia, and you ob- tain a magnificent purple color from formation of murexide.* *Uric acid C8H4N408 is like urea an azotized substance; it exists in urine chiefly in the state of an alkaline urate, and is — 57 — Quite different is oxalic gravel, which presents itself under the form of fine sand, of a bluish gray, Fig.i. Fig.2. and not red color. If you examine this sand under the microscope, it is no longer the appearance of a whet-stone or lozenge, but that of a star, or rather of deposited when the urine is cold, under the form of crystals of a reddish, yellow or bright red color. These crystals resemble rectangular prisms, lozenges, whet stones, etc, sometimes several crystals are grouped together and form stars or rosettes. Uric acid is feebly acid; it does not redden litmus; in- soluble in alcohol and ether. In fact, in order to dissolve one part of uric acid, you need 15,000 parts of cod water, and 18,000 of boiling water; it dissolves wholly without decomposi- tion in concentrated sulphuric acid. It is precipitated from its solutions by acetate of lead. Heated in a test tube, it gives rise to urea, cyanuric acid, hydrocyanic acid, carbonate of am- monia, and alloxan. Treated by concentrated nitric acid, uric acid breaks up into urea and alloxan. The latter, under the influence of a few drops of ammonia, or even of ammo- - 58 - a closed envelope, which is presented by these crystals of oxalate of lime which constitute oxalic gravel, and it suffices to compare the following figure (Fig. 3) with the foregoing figures to see clearly the difference which from a micrographic point of view separates oxalic from uric gravel. Here you no longer get the violet coloration by nitric acid and ammonia, but if you add sulphuric acid and raise the temperature, gases will be liberated, con- niacal vapors, turns to a reddish purple color (purpurate of ammonia), which by the addition of caustic potash, becomes bluish purple. The murexide observed by Scheele, studied and design- ated by Proust under the name of purpurate of ammonia, crystallizes in quadrangular prisms, or in tables which are green by reflected, and red by transmitted light. These crystals, which contain a molecule of water, give those mag- nificient metallic reflections which the wings of cantharides display; they dissolve in water with a rich purple color. The following table giving the results of analysis of 1,000 cases of urinary lithiasis, shows the relative frequency of each kind: Uric acids or urates....... Phosphatic gravel........... Lithiasis of a complex nature Oxalate of lime............ Total................. A propos of the age of calculous patients, statistics have been established bearing upon the frequency and nature of these affections at different periods of life. As for the relative frequency, these are the results of a study by Civiale of 5,376 cases: 372 263 233 232 1000 - 59 - sisting of carbonic acid and carbonic oxide. So much for the acid urines. Does the urine present an alkaline reaction ? The sediment is almost always ammoniacal, and constituted by calculi of ammoniaco-magnesian phosphate, pre- senting themselves to the microscope under their characteristic coffin-shaped crystals (Fig. 4). You will also sometimes find a calcareous lithiasis in alka- Fig. 3. Fig. 4. From 1 to 10 years of age....................... 1946 From 10 to 20 years of age................. ... 964 From 20 to 30 years of age...................... 460 From 30 to 40 years of age.................... 340 From 40 to 50 years of age..................... 391 From 50 to 60 years of age..................... 513 From 60 to 70 years of age.................... 577 From 70 to 80 years of age................... 199 A bove 80 years of age......................... 17 As for the nature of the calculi, the following variations have been noted according to the age of the subjects: 1. In infancy and adolescence, there is predominance — 60 — line urines formed by amorphous strata of tribasic phosphate or carbonate of lime. The ammoniaco-magnesian phosphates (2Mgo, NH4 POs4-i2H80) crystallize in voluminous prisms with rhom- boidal base, when you examine them after their natural deposi- tion in ammoniacal urine. In acid urine and in fresh urine, the phosphates do not form a precipitate; to obtain such pre- cipitate in fresh urine you have to add several drops of am- monia; in these cases the crystals no longer present themselves under the form of rhomboidal prisms, but they take on the aspect of needles, stars, and arborizations. The ammoniaco-magnesian phosphate is insoluble in water and ammonia; it is precipitated from its solutions by the alkalies and ammonia; it is soluble in acetic acid and in the mineral acids. Lastly, to complete the subject, I may tell that you there exists an indifferent lithiasis characterized by calculi of an extreme rarity and which I will only men- tion, namely, cystic gravel constituted* by cystine, and xanthic gravel. Cystine (C8H5 N So8) is found in urine ordinarily in the state of a sediment mingled with urate of soda, or under the form of a calculus. It was discovered by Wollaston in 1805. The crystals of cystine appear in the form of six-sided lamellae. Deposits of cystine are iasoluble in the warm urine, or in warm water; they are dissolved by ammonia, and if the of oxalate of lime calculi, sometimes associated with the car- bonate. 2. In adult age, calculi of uric acid and urates predom- inate. 3. In old age we oftener observe calculi formed of the earthy phosphates and carbonates. — 6i — ammoniacal solution be allowed to evaporate, the six-sided crystals are again deposited. To differentiate them from uric acid, treat them with some mineral acid, which dissolves cys- tine, while leaving uric acid crystals intact. Treated by HC1, zinc or tin, cystine gives off sulphuretted hydrogen. Xanthine (CBH4N4Osj, discovered by Proust, is a rare form of urinary calculus. When dry, it forms an amorphous, yel- lowish white powder, very sparingly soluble in cold water, rather more freely in hot water. If dissolved in nitric acid, and the solution evaporated by heat, xanthine leaves a yellow residue which assumes a reddish yellow color on contact with potassium hydrate solution, and this, when heated, turns violet red. When you have ascertained the nature of the lithiasis, you can institute a treatment which shall, on the one hand, be directed to the cause, and on the other, to the removal of the gravel; and you will see that, according to the kind of deposit, the management of the case will be different. Let us, then, examine suc- cessively from this point of view, uric gravel, then oxalic and phosphatic gravel. Three great causes: diathetic, dietetic and renal, favor the formation of uric gravel. i. The uric diathesis, what Bouchardat calls the polyuric diathesis, is a frequent affection which often serves as a basis for the development of gout; and if there may be uric gravel without gout, it is im- possible to have the latter without uric gravel; we see even the children of gouty patients subjects of this gravel, which is also a morbid complication in most arthritic complaints. — 62 — 2. The alimentary causes of uric lithiasis have been long known. Results of the incomplete com- bustion of azotized matters, uric acid shows itself whenever the diet is too rich in albuminoid matters, or to be more precise, whenever the diet is not pro- portioned to the work and to the combustiens of the economy; in a word, uric lithiasis is the gravel of the rich man and the citizen. Already in my lectures on regimen* I have shown yofi the evils of a diet too largely azotized, and among these evils I have given the first place to the uric diathesis.f 3. As for the local diseases of the kidney, they may, by a mechanism which I shall soon explain, be- come the point of departure of gravel. When we come to study the intimate mechanism of the three causes above given, we find difficulties of a serious nature, and I ought here to enter into cer- tain explanations. *Diseases of the Stomach and Intestines. Part 1. (Am. Ed.) fThe causes of the uric diathesis are the following: An excessive nitrogenized diet, and the abuse of fatty food and of sweets; 2, the prolonged use of alcohol, and of certain wines, in particular of the effervescent wines, as well as of strong beer; 3, a sedentary life and insufficient exercise, over- work of mind, mental emotions and grief; 4, the suppression or the diminution of the cutaneous functions; 5. dyspepsia, which may result from the uric diathesis, but which also may aug- ment the production of uric acid; and accord ng to Lasegue it is almost always in a trouble of the digestive functions that - 63 - It was once thought that in order for uric acid gravel to be brought about, it was necessary simply that the uric acid should be in greater quantity than it ought to be in the blood, as this increase would manifest itself by an augmentation of the uric acid in the urine; at the same time, if in the immense majority of cases we note this increase of uric acid in the blood of calculous patients, the fact is far from being a constant one, and Garrod and Beale have re- ported observations in which there was rather diminu- tion than increase in the quantity of uric acid in the circulation. Hence physiological chemists have alleged an- other reason, and have said that it was sufficient that the blood should contain certain substances which op- posed the solution of uric acid, to see the latter pass immediately into the urine, although there might not we find the cause of the superabundance of uric acid in the economy; 6, heredity. Bouchardat has established a division of urinary lithiasis according to the social position of individuals who are affected thereby. I. In the peasant, you frequently observe calculi of oxalate of lime. 2. In the rich inhaoitants of cities, given to good cheer and to idleness, calculi of uric acid predominate. 3. In rich or poor people who make an abuse of ven- ereal pleasures, you are very likely to find calculi of earthy phosphates, and this res us from the frequency of affections of the urinary passages in these patients. — 64 — be any increase in uric production. This chemical explanation has been chiefly supported by Voit, who was the first to point out the fact that uric acid, being little or not at all soluble in a solution of acid phos- phates, when the latter are in excess in the blood, they determine the appearance of this kind of gravel. Alcohol acts in the same way, uric acid not being soluble in alcoholic solutions. We might demand if we may not find in this very fact an explanation of the uric diathesis, and of the gout which is met with in certain kinds of poisoning, in lead poisoning for instance. These are very important facts, which I pray you to keep in mind; they even go to show that when we have to do with the dietary of persons who are the subjects of gravel, we should proscribe alcohol and too acid fruits. This chemical explanation of uric gravel is not the only one which has been given; authorities have also spoken of certain functional troubles on the part of the kidney. They have pretended that when the urine contains less than the normal quantity of water, it thereby presents a favorable condition for the uric diathesis. It has also been affirmed that certain func- tional disturbances taking place—according to the prevailing theories of urination, whether in the Mal- pighian glomerules, or in the tubuli contorti, have for their consequence a more free elimination of uric acid. Lastly, the presence of mucus in the urine, in deter- mining the production by fermentation of lactic acid, — 6S — augments the acidity of the urine, and in this way favors the precipitation of uric acid. To sum up, from a therapeutic point of view, we have in uric gravel two great indications to fulfill; that of diminishing the acidity of the urine, and of augmenting the quantity of water therewith excreted. To diminish the acidity of the urine, we should employ alkalies, and this method, which has been in use, empirically, since the 15th century, is the only one which can give good results, and if writers have disputed the value of the alkaline treatment of lithiasis, it is because they have forgotten the import- ant point to discriminate the kind of gravel which they had to treat. Heroic and curative medicaments in the treatment of uric gravel, alkalies have deplor- able effects when administered for alkaline gravel and this is why some of the old authorities maintained that in certain cases the alkaline treatment is more injurious than useful in lithiasis.* What alkalies should you choose ? What doses should you give, and how should they be administered ? These are important points to discuss, and thanks to * It was Basile Valentin, a chemist of the 15th century who first prescribed the alkaline carbonates. One of the most vaunted remedies for urinary concretions was that of Lady Stephens. The British Parliament, in 1739, bought this pre- scription for a large sum of money. The Academy of Sciences in France published a report on this remedy, and Morand, referee, showed that it was composed of egg shells, of soap, 6 BB — 66 — the experiments of Roberts, we are able to respond categorically to each of these questions. Roberts submitted calculi of uric acid to the action of alkaline solutions more or less concentrated, and ascertained by weighing, the quantity of the calculus dissolved in a given time. He demonstrated this capital fact, that a calculus of uric acid does not dissolve in an alkaline menstruum in the ratio of the strength of the latter. When the alkaline medium contains too large a pro- portion of the alkali, it has no solvent action on the uric acid. There forms, in fact, under these circumstances around the calculus a layer of biurateof sodium which prevents the solvent action of the alkali; while, on the contrary, whefi the alkaline solution is weak, the cal- culus dissolves with greater activity. These are facts of the utmost importance, showing that it is in moder- ate and rather feeble doses that you should administer the alkalies. Roberts made also a curious experiment from which we can draw a lesson; he placed a quan- tity of uric acid of a given weight in an alkaline solu- tion of definite strength, and then reckoned what the of burned snails, of a decoction of chamomile flowers, of fennel, and of parsley. At the same epoch, the medical pro- fession was making earnest trials with alkalies, and in particu- lar with carbonate of soda, in the treatment of stone, and the Vichy waters began to have a considerable reputation in cal- culous affections. But it was not till after the labors of Magen- die, and the report of Charles Petit to the Academy of Sciences in 1829, that the question really became scientifically settled. - 67 - uric acid had lost in weight without any movement being imparted to the mixture; then, with a solution of the same strength and volume which he took care to let fall by constant dropping upon the uric acid, he ascertained the solvent action of this new solution, which proved to be very much greater than in the previous instance (when the calculus was acted upon in a still liquid), and when the flow was so slow that the alkaline solution fell drop by drop upon the gravel, the solvent action attained its maximum of intensity.* What are we to conclude from these facts ? We have a right to infer that, in order to obtain the solu- tion- of uric gravel, we should both dilute well our doses and give them at short intervals, so that the urine shall be constantly impregnated with these alka- line principles, and thus maintain a continuous solvent action on the calculus. * Roberts observed on immersing calculi of uric acid in solutions of potassa, that 12 grammes of potassium carb- onate in a pint of water are without effect upon the calculi, and it is the same with eight grammes. Six grammes per pint dissolve three per cent, of a cal- culus per day; three grammes dissolve 20 per cent.; 1.50 grammes 11.9 per cent.; 0.50 gr. 6.05 per cent., etc. Roberts, in another series of experiments, noted that in 24 hours 1.50 gr. of carbonate of potash dissolved in a pint of water had upon a calculus of uric acid the following action: 45 pints without flow dissolve 13 per cent, of the calculus; 8 pints with continuous flow, 10 per cent; four pints with continuous flow, 9 per cent.; two pints' flowing drop by drop, dissolved 17 per cent, of the calculus. — 68 — You understand, of course, that I am speaking only of the possibility of the solution of uric gravel; when the stone is formed in the bladder, the result is much more doubtful, and notwithstanding the curious facts signalized by Debout, and still more recently by Constantin Paul, of the spontaneous fragmentation of stones in the bladder, I believe we cannot count on lithontriptic medication (if there be any such) to attain this end. What is the alkali to which we should give our preference? In England practitioners administer potassa and lithia; in France, we prefer soda. We will consider these in their order. In England they give the citrate, acetate, and carbonate of potassa; the English physicians affirm that uric acid is more soluble in potassa than in soda, and Roberts counsels the liquor potassce of the English pharmacopoeia, and especially the citrate of potassa, in the dose of 12 to 16 grammes per day, taken in divided doses every three hours.* *Citric acid is tribasic, its formula being Ci3H5Oil3KO. it is made (U. S. and B. P.) by saturating potassium bicarbon- ate with citric acid. The dose is from 20 to 25 grains. The Liquor Pot. Cit. is officinal; dose § ss to § ij. Potassce ace/as (acetate of potassa) is made by saturating bicarbonate of potassa with acetic acid. It is a white salt, neutral to test paper, of warm pungent saline taste. Has been called foleated earth of tartar. It is very soluble in water, and is deliquescent. It is diuretic in the dose of a scruple - 69 - If you adopt the English treatment, I advise you to employ the following potion: Citrate of potash, 12 to 15 grammes. Infusion of arenaria rubra, 90 grammes. Syrup of 5 roots, 30 grammes. [May be replaced in American practice by the following: 3 Pot. citratis, 1 ss. Syr. scillae, § i. Infus. scoparii, § v. M. Sig.—A tablespoonful three or four times a day.] to a drachm; in the dose of 3 ij to 3 iij it is purgative. For a diuretic effect, it should be largely diluted. Potassa carbonas (carbonate of potassa) is obtained from crude pearlash by purification, or from cream of tartar by incineration. It is a coarse, granular, white powder, with nauseous, caustic, alkaline taste, very soluble in water, insolu- ble in alcohol. The dose is from 10 to 30 grains largely diluted. Liquor Potassce.—(For mode of preparation, see U. S. P.) The dose is from 10 to 30 minims very largely diluted in sweetened water or some mucilaginous fluid (infus. aurantii cort. is a good menstruum). Lithia is a white crystalline substance of caustic taste. (For mode of preparation of lithia and its carbonate, see U. S. P.) The carbonate is the salt generally employed. It is a light, white powder, which is but little soluble in water. It may be associated with carbonate or citrate of potassa. The dose of carbonate of lithia is 3 to 6 grains, which may be taken in carbonic acid water. The citrate of lithia is an eligible salt, which is less disagreeable than the carbonate; the dose is from 5 to 10 grains. — 7° — For my part I am not very partial to potassa as a medicament for habitual use. The salts of potash are very active, and I have already told you, when speak- ing of purgatives, the great difference which exists between the potassium and the sodium salts in the r effects on the economy. This difference exists throughout the entire series of the potassium salts as compared with those of sodium, the first having a manifest depressant effect on the economy. Bouchard has long insisted on the toxicity of potash, which he says is 60 times greater than that of soda; as this toxic action manifests itself in cases of renal in- sufficiency, you understand the dangers which may at- tend the use of the potassium salts in the treatment of urinary lithiasis. Hence, I much prefer lithia to potassa, and were it not for the high price of this base, it would be likely in my judgment to supersede the other alkalies in the treatment of uric lithiasis. Lithia is given in the form of carbonate or citrate, in doses of from 3-5 grains three times a day. I think that you should not exceed the latter dose, and I cannot endorse Charcot's method, who gives as much as 30 grains of lithia in the 24 hours; given in such doses, the lithia salts are sure in a little while to bring on fatigue of the stomach and digestive troubles. The carbonate of lithia has this important pecul- iarity, that it is soluble only in carbonic acid solutions. Hence, in administering it, you will have to stir your dose of lithium carbonate into a little artificial soda or — 71 — Seltzer water, or some one of the natural gaseous waters. A good way is to give your lithia salt in a glass of water along with the ordinary effervescent powders of sodic bicarb, and tartaric acid; in this way you give your patient a combination of lithia and soda. You can also make use of the granular effervescent salts of carbonate or citrate of lithia, or the syrup of lithia made according to Duquesnel's formula. Soda, if it does not possess all the energetic effects of lithia, presents nevertheless an advantage that it is of moderate price. We generally order either the bicarbonate of soda in substance, or the sodic-bicarbonate waters. An excellent method is the administration of effervescent powders, of which one contains one drachm of bicarbonate of sodium, the other a scruple of tartaric acid. The bicarbonate of soda is given in solution in the dose of two to three grammes a day, but the usage of the natural alkaline waters is much to be preferred. Choose especially (and here you can fall back on the experiments of Roberts as the basis of your treat- ment) mineral waters containing a feeble quantity of sodium bicarbonate, 2 to 3 grammes to the litre, and among the Vals waters prescribe, Saint Jean, and among the Vichy waters the springs of Hauterive, of Celestins, and of Saint-Yorre. To these spas, you may join Boulon, Velleron and Chaudes-Aigues, in France, Ems in Germany, and Bilin in Bohemia. Bouchardat recommends that these waters shall — 72 — be taken with light white wines, sometimes slightly acid, such as are obtained from the centre of France. These light wines, when diluted with the alkaline water, constitute a very agreeable beverage, present- ing this great advantage, that the combination of the two forms a real tartrate of potash and of soda, which has a favorable action from the point of view of the solution and expulsion of the uric gravel. Has this alkaline treatment, to which we give the first place in the therapeutics of uric gravel, any evils as well as advantages ? It has been asserted that the prolonged usage of alkaline waters has an injurious action on the blood, and particularly on the red blood corpuscles, and that anaemia is the inevitable consequence of this kind of treatment. Trousseau is mainly responsible for hav- ing created in its entirety the alkaline cachexia, which he believed to be the result of the deglobulizing action of alkalies. Since Trousseau's time, the experimental method has been perfected, and we may to-day affirm that alkalies are rather medicaments favoring and regulating nutrition than enfeebling to the organism. Coignard had already shown us that alkalies aug- ment and improve the combustions of the economy, but it is chiefly to the remarkable experiments of Hyades and Martin Damourette that we owe the scientific demonstration of the favorable action of these medicaments on nutrition. Lastly, the researches of Pupier and Lalaubie, who have always noticed — 73 — under the influence of alkaline waters an augumenta- tion of the globular richness in the anaemic, show us that there is little foundation for this bugbear of the alkaline cachexia, which is based rather on theoretical and preconceived notions, than on clinical and experi- mental facts rigorously observed. Trousseau described an alkaline cachexia similar to what is observed after the long administration of iodine and the mercurials. It is, he said, characterized by emaciation, pallor, a general bloated appearance, passive haemorrhages and serous effusions. This cachexia was based on the deglobulizing in- fluence of the alkalies. According to Gubler, this baneful action is due to the fact that while the salts of soda abound in the serum, salts of potash predominate in the corpuscles; if you augment in too great quantity this soda in the serum, the globules lose their potassa, and in consequence their haematic properties. Climent had even found by Malassez's system of enumeration, a notable diminution of the globules under the in- fluence of alkalies, and Rabuteau had • maintained that the alkalies notably diminish the figure of urea-production. All these facts have been taken up anew, and it appears to be demonstrated that if, as Lomikowsky has done, we may determine in dogs, like those to which he administered daily and for a long time half an ounce to two ounces of bicarbonate of soda, accidents of a grave kind, and in particular very in- tense digestive troubles, in man, on the contrary, you always augment the figure of urea as well as that of the globules, and the experiments of Mialhe, of Coignard, and others mentioned above, seem in this respect to be absolutely demonstrative. Alkalies, then, act in therapeutic doses as excitants and regula- tors of nutrition, whether through their influence on the ner- vous system, or some unknown cause. While recognizing the fact that the alkaline ca- — 74 — chexia is largely a myth, it must be admitted, never- theless, that when abuse is made of the alkaline waters, and in particular of the alkaline salts, there may supervene a notable fatigue of the stomach, and in this respect there is a very marked advantage in the use of the natural over the artificial mineral waters. The first are tolerated, even in large doses, without provoking any digestive troubles, the alkaline solutions are, however, as I have just told you, painful and fatiguing to the stomach. The facts whibh I have just stated also show you that it is a mistake to suppose that the alkalies act chiefly by neutralizing uric acid. Their favorable action in the treatment of uric lithiasis has quite a dif- ferent origin. Alkalies act, as Basham and Harley and other authorities above mentioned have shown, by energizing the phenomena of oxidation of the economy, and thence aiding the transformation of uric acid into urea. To the sodii-bicarbonate waters, you may add certain waters of the Pyrenees, as Laprest, Molitg, Olette, and especially Capvern, which have a real action in the treatment of uric gravel. You have fulfilled the first indication by alkalies, i". *., you have done what you can to oppose the ex- cessive acidity of the urine, you must fulfill the second indication, namely, to hasten and favor the expulsion of the gravelly deposits. You will attain this end by employing the diuretics furnished by the mineral — 75 — waters, or by the pharmaceutical preparations. Here you will witness the triumphs of the waters of Pou- gues, Vittel, Evian, Contrexeville, and of all those waters of uncertain mineralization which do not con- tain any special principle which characterizes them, but which act chiefly by their mass. You may also recommend the silicious and lithiated waters, like those of Evaux, and Sail les Bains, which have a very ener- getic diuretic action. To these mineral waters, you may add the action of certain rnedicaments. You may draw freely from the great group of diuretics spoken of in a previous lecture. The vegetable diuretics may here serve you a good purpose, and in particular the Arenaria rubra, the diuretic action of which has been lately so much extolled, or the Stigmata of maize, which has so recently come into vogue. Arenaria rubra (red sandwort) is obtained from the shores of Algeria. The decoction (i ounce to the Oij) is an excellent diuretic, and may be freely taken for this purpose. Stigmata of maize (corn-silk) has lately come into use in this country, though long employed in Mexico. An ounce of the corn-silk to a pint of hot water makes a good infusion which may be freely drank. There is a fluid extract which is much in use; dose, a teaspoonful 3 or 4 times a day. By the side of these alkaline and diuretic medi- cines, we must place a medicament whose action is quite different, and which has the property of trans- forming into hippuric acid and soluble hippurates the insoluble uric acid and urates; I allude to benzoic - 76 — acid, or rather the benzoate of soda, which is admin- istered in the dose of 2 to 3 grammes a day, alone, or associated with acid phosphate of soda. But these medicines must yield the palm to the hygienic treatment; this it is that dominates the thera- peutics of uric lithiasis, because addressed to the very cause of the gravel. You should, then, bestow all your care in regulating the diet of your lithaemic patients, and the diet should be made to correspond to the exercise taken. Food too rich and too stimu- lating should be forbidden; the dark meats and especially game should be eschewed, and the alcohols should be proscribed; we have, in fact, seen that the latter leads to the precipitation of uric acid in the urine. Make your patients adopt a mixed diet (/. e., meat and vegetables in about equal quantities). Prescribe exercise which is such a powerful promotor of the interstitial combustions of azotized matters; require the patient to take long walks, practice gymnastics, and the more sedentary the life of your patient, the more active should be these forced exercises. Bou- chardat has traced with the hand of a master the prin- cipal hygienic indications applicable to the uric diathesis, and I cannot do better than refer you to what he has said under this head. Under the head of diet, Bouchardat advises to eat ££S£:cut the food fineIy with the knife; —*■* Abstain from sorrel and tomatoes, from asparagus. — 77 — and green beans, if their usage causes renal pain or slight deposits in the urine. Meats of all kinds agree, but they should be used moderately. Be chary in the use of eggs, fish, cray fishes, shrimps, lobsters, shell fishes and old cheese; milk is often useful. Almost all the vegetables of the season agree and should make part of the daily fare; spinach, lettuce, chiccory, artichokes, cucumbers, salsify, cardoons, celery, carrots, turnips, sweet potatoes. Potatoes are useful, and ought in part to take the place of bread. Radishes may be eaten freely; cabbages, cauliflowers, sour krout, mushrooms, truffles, chest- nuts, pea-nuts, filberts, beans, peas, lentils with moderation. Cresses, greens and lettuce should be freely indulged. All the fruits, if the stomach bear them well; strawberries, rasp- berries, peaches, bananas, apples, grapes, currants, cherries, pears, prunes, plums, pumpkins, cucumbers are advantageous, and should be made a part of the daily fare. Olives, almonds and nuts of all kinds should be sparingly eaten. Chocolate may be allowed for a drink, and coffee, if it be found to be diuretic. Prohibit brandy, and all other spirituous liquors, as well as beer. The only alcoholic beverage allowed is a light red or white wine diluted with twice its volume of water. The effervescent wines are contra-indicated, as well as water highly charged with gas, like the seltzer. Take on waking, on going to bed, and at meals, enough liquid of some kind, so as to pass about a quart and a third of urine in the 24 hours. These aqueous drinks should be: pure water, Vals (St. Jean) water, decoctions of couch grass, cherry tops, ash leaves, linseed, etc., or better still, a quart of water in which is dis- solved one or two teaspoonfuls of Rochelle salts. Under the head of excretions, he urges the importance of regularly and completely emptying the bladder every six _ 78 - hours at least. A good walk after each meal, and efforts at defecation will help the patient to accomplish free urination. At least one full stool every day is necessary. If any laxative is needed, one or two teaspoonfuls of white mustard seed or flax seed along with the breakfast may answer the pur- pose. Or, if this fails, from a teaspoonful to a tablespoonful of Rochelle salts in a glass of lemonade may be taken the first thing in the morning. Under the head of exercise, Bouchardat urges the import- ance of gymnastics and other physical exercise that shall call forth all the forces. All chilling of the body not followed by reaction is to be avoided. Any exercise (as of the arms) that augments pulmonary expansion is good. Parlor gym- nasiums (apparatus provided with elastic cords) exercise well the thoracic muscles and expand the lungs. Dum bells will do, in default of anything better. Wood sawing and chopping are especially to be recommended, and whatever exercise the pa- tient takes should be sufficiently vigorous to provoke sweating. Then the patient should have a good rub down, and change his clothes. Active exercise is the most efficacious prophylac- tic treatment. Under the head of care of the skin, Bouchardat advises a sponge bath in the morning, followed by long and vigorous rubbing with a dry towel and the flesh brush; then massage with the hand well ointed with sweet oil. At the same time, large and deep inspirations should be taken. Every week from one to three hygienic baths: 3 ounces carbonate potassa, i drachm essence lavender, 1 drachm tincture of benzoin to the water of a bath. These baths should be followed by fric- tions and massage. Sea or river baths, if indulged in, should be of short dura- tion, and followed by rubbing and exercise. There is another kind of abnormal acid gravel to which I must allude, namely oxalic gravel. This kind — 79 — of deposit is found only occasionally or accidentally in the urine, and this fact clearly separates it from the preceding. While we have seen that uric gravel is ordinarily the result of a disturbance in the nutritive processes, in oxalic gravel we can allege but one cause, the introduction by food of vegetable substances con- taining oxalic acid. In fact, this is the gravel of in- dividuals badly fed, of the peasant, the poor man. Proust, Bird, Garrod, Furbringer, and more recently Ralfe, have contended that there is an oxalic diathesis, but I believe, with Lecorche, that this diathesis is far from being demonstrated, and till further enlightened on the subject, we are to consider oxalic gravel as a simple accident, and the experiments of Esbach are absolutely confirmatory of this view. The more prob- able view then is that oxalic acid is never found in the urine except when introduced by the food.* * Furbringer claims that oxalic acid is a constant product of the urine, and that its daily elimination does not exeeed 24 milligrammes. Bicarbonate of soda does not augment the production of oxalic acid, nor do febrile processes increase its elimination- According to Ralfe,\ the sources of oxalic acid in the blood and in the urine are the following: 1. Certain ingesta: rhubarb, sorrel, tomatoes, onions, turnips; contain it, and in some persons cause digestive troubles and temporary oxaluria. 2. Incomplete oxidation of saccharine or oleaginous t London Lancet, Jan. 12th, 1882. — 8o — The difference in the pathogeny of these kinds of gravel entails a great difference in the thera- peutic indications. Here the first indication to fulfil is dietetic, namely, the suppression of aliments containing oxalic acid, and as it is in gooseberries, tomatoes, garden rhubarb, and especially sorrel, that we meet with this acid, you should proscribe these substances. Coming from these two sources, the oxaluria does not determine any disturbance in the general health. 3. Exaggeration of the interstitial nutritive processes under the influence of most febrile affections, pulmonary and cardiac affections with dyspnoea, disturbances of the hepatic functions, and an asthenic condition of the nervous system. This etiological variety is very frequent. 4 Mucus in the genitourinary passages; such is pro. bably the origin of the large crystals of oxalate of lime found so frequently in the urine in spermatorrhoea. It is possible that the deposits of oxalic acid which form in the urine of ataxic patients, especially at the epoch of the urinary crises, are due to a modification of the state of the mucosa, associated with troubles of the innervation. 5. Acidity of the urine. Esbach has proved that a great number of aliments con- tain oxalic acid, and the list given below shows the quantity of this acid in divers articles of food. SPICES AND CONDIMENTS. Black tea............................... Cocoa.................................... Chocolate................................... Coffee (artificial admixture of retail dealers) Chiccory-coffee............................ Pepper................................... 3-75° 3-5»o 0.000 0.127 0.795 3-25° — 8i — articles of food. Bouchardat recommends also to in- terdict the gaseous beverages, effervescent wines, sparkling beers, the natural and artificial gaseous waters, and counsels the use of a varied and restorative diet. Moreover, be guided by the curious analyses of Esbach, who has examined the various articles of food and condiments to ascertain how much oxalic acid they contain. You will not be surprised to learn that tea, 2. FARINACEOUS SUBSTANCES. White bread.,................................... 0.312 Potatoes......................................... O.o46 Bread of good quality............................0.047 Barley flour...................................... 0.039 Wheat bran.................................... 0.848 3. VEGETABLES. Sorrel .......................................... 3.630 Spinach........... ........................... 3.270 Garden rhubarb.................................. 2.466 White cabbage....... ......................0.003 Beets........................................... 0.3^0 Green beans................................... 0.212 Tomatoes.......................... ............ 0.053 Celery.......................................01025 4. FRUITS. Dried figs........................................ 0.370 Currants....................................... o. 137 Prunes............................................ o. 120 Raspberries....................................0.062 Oranges.......................................0.030 Citrons........................................... 0.030 Cherries......................................... 0.025 Strawberries.................................... 0.012* ♦Esbach on Oxaluria, (Bull de Th<5rap, 1883, t. CIV, p. 385.) 7 BB — 82 — cocoa, chocolate, pepper, contain per kilogramme more oxalic acid than sorrel, namely from three to four grammes. But remember this important fact, that milk never determines the presence of oxalic acid in the urine, hence a milk diet is excellent for pa- tients afflicted with oxaluria. Such are the principal indications pertaining to the hygienic treatment of ox- alic gravel. You ought also to endeavor to dissolve these cal- culi of oxalic acid, or to expel them, and here you will understand the importance of an exact knowledge of the kind of lithiasis you have to treat. In uric gravel the alkalies have the first place; in oxaluria their role is nil, and these medicaments are useless. In fact, as Roberts shows, oxalic acid and the oxalates are not attacked by alkalies, which can only act when there exist, as sometimes happens, mixed calculi, i. e. con- taining oxalate of lime and urates. There remain the diuretics, and we have here medicines which are of considerable use in oxaluria, such as diuretic infusions and mineral waters. Gold- ing Bird speaks favorably of vegetable infusions, such as compound infusion of gentian, balm tea acidulated with a few drops of aqua regia, etc. The mineral acids (nitric, nitro-hydrochloric acid, sulphuric acid, acid-phosphate of soda) have been advised by eminent authorities in oxalic gravel; perhaps this mode of treatment is more theoretical than practical. I pass now to the treatment of alkaline lithiasis. _ 83 - There are two kinds of alkaline lithiasis, the cal- careous and the ammoniacal. The calcareous lithiasis is chiefly characterized by the presence of the phos- phates of lime in the urine, and writers have even spoken of a phosphatic diabetes, i. e., an exaggerated production of these phosphates in the urine. You must remember, however, that these phosphatic salts when in excess in the urine are not deposited under the form of calculi, but are held in solution because of the temperature of the urine. When, after being voided, the urine cools, they are precipitated in the form of a whitish, lactescent deposit. If these phosphates ever constitute calculi, this is a very rare occurrence. The case is different with the ammoniacal salts, which not seldom cause urinary concretions. The ammoniaco- magnesian phosphates oftener constitute vesical than renal calculi. This lithiasis is due to fermentation of the urea, and its transformation into ammonium car- bonate. Therapeutically, then, the first indication will be to oppose this fermentation, in whatever way it may have originated. Ammoniacal fermentation of urine is due to one of three causes: retention of the urine, inflammation of the kidneys, ureters, and bladder, or to trophic dis- orders; but, as Pasteur has shown, all these causes come together under one head—the production of a special torula, which, acting as a true ferment, deter- mines the transformation of urea into ammonium car- bonate. — 84 - We are still ignorant as to the real causes of the production of this ferment, but we know that when the urine contains pus, mucus, or blood, or remains long in the bladder, this fermentation takes place. Moreover, repeated catheterizations, whether by getting up an inflammation, or by conveying germs, produce the same effect. Nevertheless, this question of urinary fermenta- tion in the bladder is very obscure, and for proof of this, I need only allude to the influence which trophic disturbances exercise upon this ammoniacal transfor- mation. Take, for instance, two patients, both affected with paraplegia. Both have retention of urine, both have been sounded the same number of times, with the same instruments, and, nevertheless, one of them shall have ammoniacal transformation of the urine, while the other shall remain for months without any alteration of the urine taking place. The cause of this difference lies in the fact that in the first paralytic the disease is due to a profound lesion of the cord, while in the second, the paraplegic symptoms are the ex- pression of a functional disorder of the nervous system, of the nature of hysteria, for instance. Whatever may be the cause, the therapeutic indi- cation in these cases is very simple, namely, to modify as far as possible the urine, so as to prevent the am- moniacal transformation. We accomplish this in two ways: by means of certain essences and resins which, when introduced into the system as medicines, pass - 85 - out by the urine and favorably modify its properties, and by certain antiseptic substances. We fulfill the first indication by the employment of plants containing essences, like buchu, boldo, and santal. Buchu leaves are furnished by three species of barosma or diosma, growing at the Cape of Good Hope. These leaves contain (i), a volatile oil which when exposed to the cold fur- nishes a camphor very soluble in carbon-bisulphide; (2), a resin and a bitter extractive. The infusion is made by steeping one ounce of the leaves in a pint and a half of water down to a pint; dose, a wineglassful. The tincture is given in teaspoonful doses; the fluid extract in the dose of 10 to 30 drops. There are three kinds of sandal wood in the market, the white, yellow and red. The white and red have little medicinal virtue. By distilling the yellow sandal wood (santalum citrin- um), a volatile oil is obtained, the essence of sandal, which is administered in capsules in the dose of from 10 to 30 drops.* The turpentines and resins have the same action, and I must especially call your attention to a remedy which has gained a world-wide reputation in the treat- ment of ammoniacal gravel, namely Harlem oil, which is obtained by the distillation of juniper. Juniper (juniperus communis), as you know, is an evergreen shrub which is a native of Europe, and grows in many parts of the United States. The fruit and tops are officinal. This shrub owes its medicinal virtues chiefly to a volatile oil which it contains. The dose of this oil is 2 to 5 drops. The officinal preparations are the *For remarks on Boldo, see " Modern Treatment of Diseases of the Liver," of present series, page 131. — 86 — infusion and the oil. The peasantry in the south of France prepare from the wood of the trunk and branches a sort of tar which they call oil of cade; mixed with the essential oil of juniper, it constitutes Harlem oil. In these cases of lithiasis I often prescribe a pill made by rubbing together Venice turpentine with the soft extract of cinchona. This pill weighs just two grains, and is composed of equal parts of the two in- gredients. The dose is three pills after breakfast and dinner. Within the past two years a new remedy has been introduced, which comes from Chili, and is called pichi (fabiania imbricata). This plant is said to have a special elective action in catarrhs of the urinary passages. In the United States a fluid extract is in use, which is a good preparation, and may be given in frequent doses of half a drachm. There are certain substances of an antiseptic nature which may be used internally, such as the ben- zoate of soda, salicylic acid, and resorcin. The latter has been made a special study by me in this hospital, and my pupil Hippocrates Callias has made these clinical experiments the subject of his inaugural thesis.* *Resorcin (C6H4 OH5), a body similar to phenic acid, was discovered in 1880 by Hasiwetz and Barth. It was first obtained from certain resins such as asafcetida, galban- um, and ammoniacum. It has since been made in the - 87 - Lastly, in certain cases, you can act directly on the bladder by injecting liquids destined to prevent fer- mation—solutions of chloral, carbolic acid, and especi- ally boracic acid. In making these injections, you can employ a double or single catheter, and the ordinary pear- shaped rubber-ball injector. These injections should be tepid, and when there exists paresis of the bladder, it has been advised to give them warm—1040 F. to 1120 F.—with the intention by the heat of stimulating the contractions of the vesical mucous membrane. These little measures, which belong rather to surgery laboratory by synthesis. Resorcin is found in commerce under three forms: 1. Large garnet colored crystals, of strong phenic odor; this is the impure product of commerce. 2. Prismatic needles of rose color and almost odor- less. 3. Chemically pure (obtained by Monnet's process) in very fine, sparkling-white needles); this is medicinal resorcin Omitting the physical properties, and considering resor- cin therapeutically, we find it to be antifermentative, and antiseptic, caustic in concentrated solution, and haemostatic; it coagulates albumen. It has also antithermic properties. Taken internally in the dose of from 1 to 2 grammes, it is rapidly eliminated by the urine, in part unchanged, and in part under a form yet unknown. This urine becomes of a deep brown color on exposure to the air. Treated by per- ehloride of iron (when resorcin is present in sufficient quantity), you obtain with an abundant white precipitate, a deep violet coloration similar to that obtained with salicylic acid. Resorcin — 88 — than to medicine, are of considerable importance, for vesical catarrh and its consequences are extremely frequent in male patients when they have attained an advanced age. But here the dominant indication will be to pre- vent the sojourn of the urine in the bladder. You ought then to insist on the patient urinating as often as possible, and if the bladder is too inactive, or the prostate too voluminous to enable the vesical muscle to empty the viscus completely, you should urge the necessity of the use night and morning of the soft rubber catheter, whereby all the urine shall be drawn off and not allowed to remain long enough in the is toxic in large doses like phenic acid; in the dose of 30 centi- grammes per kilogramme of the weight of the body, it produces convulsions, which may be compared to electric shocks suc- ceeding each other at short intervals. In the dose of one gramme per kilogramme, it is rapidly fatal, the animal dying in 30 seconds with convulsions. Resorcin has been given internally in fever with anti- thermic intent, and recently Peradon has brought together a certain number of cases occuring in the service of Dr. Desnos. These observations tend to prove that if resorcin has no cura- tive action in rheumatism, it notably brings down the tempera- ture in typhus and typhoid fevers. The dose as an antithermic is 30 to 45 grains, this quantity to be administered in divided doses during the twenty-four hours. (Callias, On the Employ- ment of Resorcin in Therapeutics, These de Paris, 1881,— Dujardin-Beaumetz and Callias, On Resorcin, and its Employ- ment in Therapeutics, 1881, Peradon, On the Employment of Resorcin in Therapeutics, These de Paris. 1882, etc, etc. - 89 - bladder to become decomposed and deposit strata of ammoniaco-magnesian phosphates. If there are means which are useful in the treat- ment of ammoniacal lithiasis, there are also means that are dangerous. The prolonged use or abuse of alkalies, by augmenting the alkalinity of the urine, is sure to do harm. Hence you see the necessity of what I insisted upon at the beginning of this lecture, namely, the determination of the nature of the lithiasis which you have to treat, and while you have seen that alkalies are heroic and curative in uric lithiasis, they can to nothing but harm in the treatment of ammonia- cal lithiasis. Such are the principal therapeutic indications in lithiasis; it now remains to study the accidents which it may determine, and this brings me to the subject of the complications of lithiasis. CHAPTER IV. TREATMENT OF THE COMPLICATIONS OF LITHIASIS. Summary.—The Complications of Lithiasis—Nephritic Colic— Symptoms of Nephritic Colic—Pathogeny—Therapeutic Indications in Nephritic Colic—Hydrothermal Treatment —Renal Hemorrhages—Diagnosis of Hematuria—Treat- ment of Hematuria—Inflammations of the Ureters and Renal Pelvis—Pyelitis—Treatment of Pyelitis—Renal Calculi—Hydronephrosis—Calculous Anuria. In the preceding lecture I have considered urin- ary lithiasis and its treatment; to-day I call your at- tention to the remedies which are employed against the complications which arise from the presence of the gravelly deposits. Three orders of accidents may occur; first, the acute painful phenomena determined by the passage of the gravel down the ureters when these foreign bodies travel from the pelvis of the kidney to the bladder. You know that there has been given to this symptomatic aggregate the name of nephritic colic. Again, these calculi, by irritating either the pelvis of the kidney or the ureter, or even by sojourning in the bladder, may determine inflammation or hemorrhage. Finally, in certain cases when the calculus has obliterated the ureter, it causes a distention of the pelvis which soon involves the kidney itself and trans- _ 91 — forms it into a cystic pouch; this is hydronephrosis. Moreover, you easily understand that if by any un- favorable coincidence the other ureter should be obli- terated, anuria and uraemic complications will arise, being the consequence of the sudden arrest of the renal functions. Let us study these complications successively. Nephritic colic, much the most frequent complication, presents a very characteristic array of symptoms, which you will find described in your text books on Practice of Medicine. You will there see signal- ized that peculiar sharp pain, so intense at times that it causes the patients to make loud outcries and ask for death to put an end to their sufferings. This pain extends from the affected kidney to the in- guinal region, and even to the testicles. It is a mo- bile pain, changing its place as the calculus travels downward, and suddenly ceasing when the foreign body, having cleared the vesical orifice of the ureter, falls into the bladder. As in hepatic colic, vomiting supervenes, with cold sweats, lipothymia, and some- times even mortal syncope. In the midst of this gen- eral disorder and this incessant agitation the pulse remains calm, and is even sometimes slower than natural. Nephritic colic does not always have a sudden onset; sometimes there are sensations of tingling and numbness in the region of the kidneys, lasting (it may be) for weeks before the onset of the nephritic colic. — 92 — In other cases, it is a malaise and a painful sensation at the epigastrium which precedes the painful symptoms; then appears the characteristic pain. This pain is piercing and is always on the affected side; it is increased by pressure and ex- tends over the abdomen and down to the labium majus in women and to the testicle in men; there is also a numbness extending down the thigh. The patients always experience rectal and vesical tenes- mus, they have a strong desire for defecation, and make fre- quent attempts at micturition; the urine is red, thick, and flows drop by drop; it often contains mucus and blood. Vomiting rarely is wanting, the skin is covered with a cold perspiration, the pulse becomes small, thready, finally the expression of the face changes and takes on the aspect charac- teristic of intestinal and hepatic colic (facies abdominalis). The colic may last three or four hours, sometimes even forty-eight hours, with more or less violent paroxysms, then all these symptoms suddenly cease. The patient experiences a sensation of relief, and of prostration. The urine at this stage sometimes becomes abundant. As for the offending body, the stone, it may remain in the bladder for several days, and even be the nucleus of a vesical calculus, but more frequently it passes out with the urine, and gives more or less pain in the canal of the urethra. Such is the usual course of nephritic colic, the symptoms of which are sometimes confounded with those of hepatic colic, which are distinguished by the appearance of jaundice in the one case, and then, by the seat of the pain, which differs in both cases. As for the aggregate of symptoms, it is the same in both kinds of colic, and this you will readily understand if you recall to mind the origin of the attacks of pain. — 93 — When I was speaking to you of hepatic colic, I dwelt at length upon the structure of the bile ducts, in order to show you that the painful, phenomena re- sult from a muscular spasm caused by irritation of the mucous membrane, and that this spasm produces re- flexly all the other symptoms noted in such cases. Here the pathogeny is the same; the ureters, like the bile-ducts, are lined by a highly sensitive mucous membrane, and have, moreover, an undoubted fibro- muscular tunic. When a foreign body traverses these ducts, it may determine there painful spasm, and vari- ous reflex symptoms due thereto. It is an important fact to note, that it is not by its size that a calculus determines these accidents, but by its asperities. You may have a calculus of uric acid relatively voluminous, but round, smooth, and resem- bling shot, which may traverse the ureter without pro- ducing any symptoms whatever, while, on the other hand, another stone, like the oxalate of lime calculus, much smaller in size, but rough, and with sharp pro- jections, may cause a most painful and distressing colic. All depends, as you see, on the irritation which the foreign body may set up in its passage through the ureter. The identity between the pathogeny of hepatic colic and that of nephritic colic, entails an identity in in the treatment, and I need here only refer you to what I have already stated at some length in reference to the treatment of hepatic colic: to diminish the — 94 — painful spasm, to hasten the march of the calculus, are the two indications to fulfil.* As for the first indication, you will meet it by having recourse to the three great medicines men- tioned in connection with hepatic colic; opium, chloral and chloroform. Do not forget that, as in hepatic colic, the most natural channel for the introduction of medicines is closed to us by the occurrence of vomiting, and that there remain only the skin, the rectum, and the pulmonary mucous membrane; here we witness the triumph of hypodermic injections of morphine, which have driven from the field the other preparations of opium, such as were proposed by Chomel, as well as the datura stramonium, counselled by Zaar, and the extract of belladonna, vaunted by Dubla. Chomel prescribed every hour, or every half hour, a half grain of opium in solid or liquid form. The opium has also been given in lavements composed of two tablespoonsfuls of flax-seed tea, a teaspoonful of sweet almond oil, and a couple grains of extract of opium. Zaar gave his stramonium with castor oil, while Dubla advised to rub well into the loins and abdomen, three times a day, an ointment composed of fifteen grains of extract of bella- donna, with half an ounce of lard. The hypodermic injections are to be administered in the same dose as in hepatic colic. The combina- *See Modern Treatment of Diseases of the Liver (Li- brary Series, 1888), Chapter III, p. 68. — 95 — tion of atropine (r^- grain) with morphine (% grain) is a good one; there are tablet triturates for sale in the United States which are convenient for this pur- pose. But it will not do to push the atropine too far; if your hypodermic has to be repeated, the morphine had better be used alone. Ten to.fifteen drops of Magendie's solution (morphine sulph., gr. xvi, cherry- laural water r j) may be used subcutaneously, and repeated as required. You may as I have told you, utilize absorption by the rectum, and employ suppositories of opium and belladonna, and lavements of chloral, although this method is often rendered difficult or impracticable by the incessant efforts at defecation which accompany nephritic colic. Lastly, there remains the pulmonary method, employed for the first time in 1849 by Valleix, who chloroformed a patient suffering from a horrible nephritic colic, This is, I am bound to say, an excel- lent method, and just as in hepatic colic, you should have recourse to it when the pain becomes insupport- able, but it is unnecessary to obtain surgical anaes- thesia, but simply obstetrical anaesthesia. This em- ployment of chloroform by inhalations is much supe- rior to other methods of using this anaesthetic which have been proposed in such cases, whether by mouth or by external applications.* *Aubrun has suggested the following method, viz., the application over the renal region and other painful points of the abdomen, of a compress saturated with chloroform, this compress to be covered with a watch glass. — 96 — I have given you the most efficacious, and I may say the only efficacious means to diminish the inten- sity of the painful spasm in nephritic colic. Other therapeutic agents have been proposed, which are ad- dressed rather to the second indication which we have to fulfil, /. e., to hasten the passage of the calculus. Some have suggested mechanical means, and have thought that various inclined positions might help the progress of the foreign body. Roberts held his pa- tients up by the heels; others give patients snuff to make them sneeze or endeavor to provoke fits of coughing. These manoeuvers should be all abandoned, and I may say the same of certain reflex phenomena which some have sought to bring about in the ureters, by applying blisters and "sinapisms to different parts of the body, or even by the use of hydrotherapy. I believe that these therapeutic means are inapplicable to nephritic colic. Finally, turpentine and coffee have been advised; Richter has advocated the former and Schapmann the latter remedy. But these means are directed more toward the urinary lithiasis than to the nephritic colic. The only means of hastening the progress of the calculus is by the use of diuretics, which by producing an abundant flow of urine, force onward the calculus and hasten its passage; here, as you know, we witness the triumph of certain mineral waters of uncertain mineralization, such as VitteM and ContrexeVille. And — 97 — just as we have seen persons affected with hepatic colic have recourse to the therapeutic action of the waters of Vichy and Carlsbad, so also almost all pa- tients suffering from renal gravel may use to advant- age the diuretic waters of Contrex^ville, Vittel, Evian, etc. Often, even, the action of these waters repro- duces attacks of colic, and we have here a point of re- semblance with the effects of alkaline waters on biliary calculi. Such, in brief, is the treatment of nephritic colic. Renal hemorrhages are often, as I have said, the consequence of the presence of urinary calculi, whether seated in the pelvis, whether passing down the ureter, or whether sojourning in the bladder. You readily understand that by their presence, or their rough points, they may wound the mucous membrane and lacerate blood vessels which shall thus give rise to a more or less abundant haematuria. But before treating these haematurias, it is well to verify the presence of blood in the urine. For this there are two processes; the one which is the most cer- tain consists in the microscop cal examination of the urine, which reveals the presence in greater or less number of blood globules; the other is a chemical process advocated by Almen, which is based on the blue color assumed by tincture of guaiacum in pre- sence of bloody urine. In a test tube you pour a little tincture of guaiacum mixed with an equal quantity of turpentine, then you add some urine, 8 BB — 98 — agitating it with the mixture. If the urine contains blood there will be produced a more or less intense blue color; if there be no blood, the precipitate is white or greenish. When once the diagnosis is established, it remains to ascertain the source of the blood. In the case of females, the mistake may be committed of confound- ing menstrual blood, accidently commingled with the urine at the monthly period, with blood coming from some part of the urinary tract. This mistake may be easily avoided. Then you should ascertain at what moment of micturition blood appears in the urine. If at the beginning of micturition, the urine which flows subsequently being colorless, it is probably from the urethra that the blood comes. If the blood appears at the end of micturition, it is more likely, in fact al- most certain, that it proceeds from the bladder, hav- ing accumulated at the base of that viscus. Lastly, are the blood and urine intimately mixed ? The pre- sumption is that the hemorrhage has taken place at the source of the urinary excretion, and that the seat is in the kidney, though it may be in the ureter. After having determined the presence of blood in the urine and the seat of the hemorrhage, there re- mains a third diagnostic point to settle, namely, the cause of the hemorrhage. You know, in fact, that calculi are not the only sources of bloody urine, and that this affection may be an essential and sporadic disease, like the haematuria of the Antilles, whether such disease be linked to fevers of hemorrhagic form — 99 — (hemorrhagic small-pox, hemorrhagic scarlet fever), or whether dependent on a local disease, as inflamma- tion or cancer of the kidney. The treatment of haematuria, like that of hemor- rhage in general, comprehends two great indications: i, the treatment of the cause; 2, the treatment of the symptom. We have seen how variable the cause is, and I cannot without exceeding the limits of this lec- ture take up each of these causes separately and specify the treatment proper for it.* I shall then take up here only the treatment of symptoms, and in particular those of calculous haema- turia. After having prescribed rest in bed and a re- cumbent posture, as well as demulcent and acidulated drinks, means which alone may bring about a cessa- tion of the bloody discharges when these are slight, * Spring divides the hematurias as follows: 1. Essential hematuria, in which he places the haema- turia endemic in Mauritius, and that which is witnessed in Egypt, Brazil, and at the Cape of Good Hope, Cape Natal and in the East Indies. This haematuria, called the haematuria of warm countries, is of a parasitic nature. Indeed, Bilharz, in 1851, found in the haematuria of Egypt a special distoma; in 1866 Otto Wucherer, of Bahia, found the ova of an unknown nematoid; in 1870 Cobbold, in a case of haematuria at Port Natal, met with the ova of Bilharz's nematoid; in 1872, Lewis, of Calcutta, discov- ered the presence of the embryos of the filaria of Wucherer; in 1874 Prospero Souzino found this same filaria in the Egyptian haematuria. However, despite all these researches, some au- -- IOO -- you may add, if the hemorrhage persists, astringents such as rhatany, tannin and especially ergot and pre- parations derived from ergot, as ergotine and ergotin- ine. The two latter medicaments may be advantage- ously used in subcutaneous injections; it is one of the most efficacious means of combating visceral hemor- rhages.! You may also use to advantage the oil of sandal wood, or the oil of erigeron Canadense, giving from 10 to 20 drops of either of these essential oils in thorities, and Gues in particular, deny the parasitic nature of this haematuria of warm countries. We should also place among the essential haematurias that form which Wickham Legg has described under the name of paroxysmal hematuria. 2. The organopathic hamaturias. According to Spring, such are those which result from alterations in the kidney, and here belong traumatic and calculous haematuria. 3. Dyshemic hematuria, which has been ohserved in certain diseases, such as scarlatina, variola, scorbutus, haemo- philia. 4. Toxic hematuria, haematuria due to the introduction of certain medicinal or toxic substances into the economy. To this group belongs the haematuria caused by the sulphate of quinine, and which has recently been described by Dr. Kara- mitsas, of Athens. Vulpian has also seen haematuria caused by intra-venous injections of chloral. 5. Supplementary hematuria, which is seen after the suppression of an habitual flux. fSee Diseases cf the Heart (Library Series, 1887,) p. 127- 128 (Chapter on Passive Congestions of the Viscera). — IOI -- capsules. Such is the treatment of calculous haema- turia. Like renal hemorrhage, renal inflammation, or in- flammation of some portion of the mucous membrane of the urinary passages, is often the consequence of the irritation of calculi. There is rto more frequent cause of pyelitis, which passes rapidly to suppuration; this is a disease which is often rebellious to all our therapeutic agencies. This suppurative pyelitis may subsequently extend through the ureter to the bladder. On the other hand, there is often a propagation up- wards of inflammatory affections of the urethra, the neck of the bladder, the prostate gland, to the ureter and thence to the kidney, and not only does this in- flammation attack the mucous membrane of the pelvis of the kidney, but it soon attains the renal parenchyma itself, and this is one of the most grave complications of phlegmasia of the urinary passages. These inflammations manifest themselves by the following symptoms: First, pain in the region of the kidney, especially on the affected side; this pain is in- creased by pressure, or by movements, and in particu- lar those connected with walking and the jolts of a carriage. To these local troubles, are joined certain general symptoms characterized-by fever of remittent or intermittent form, symptoms which are always present if suppuration is abundant. In the urine you will meet with the products of this inflammation, *'. e., more or less pus and blood; the pus, which is often so inti- -- 102 -- mately mixed with the urine that the urine is clear on being voided, is deposited at the bottom of the vessel when the urine is allowed to stand a few hours, ap- pearing in the form of a creamy precipitate, which under the microscope is seen to consist of pus corpus- cles, and if agitated in a test tube with liquor potassae, forms a dense gelatinous or mucous mass which ad- heres firmly to the sides of the test tube. On decant- ing some urine from the deposited pus, the presence of albumen can be detected by heat and nitric acid. In cases of this kind, the part of the physician consists in modifying the urine as speedily as possible, as well as the inflamed mucosa; and here we witness the triumph of certain balsams and antiseptics. You may employ in turn turpentine, tar, benzoate of soda, etc. One of the best preparations is a combination of oil of turpentine and the soft extract of cinchona, as in the following formula: IJ Venice turpentine, Soft ext. cinchona, aa gr. ij. M. For one pill. From three to six of these pills may be taken after breakfast and dinner. You should above all insist on a milk diet, which gives excellent results in these cases, not only as a diuretic, but as a modifier of the digestive functions.* *See Diseases of the Stomach and Intestines, (Win, Wood & Co.) page 121, 138. — J°3 — I shall not say much about the surgical inter- ference proposed in these cases. Moved by the duration of these calculous nephrites, and the little success attending the medical treatment, certain surgeons have proposed for these states two sorts of operations; the one consists in ablation of the dis- eased kidney; this is the nephrectomy which Prof. Leon Le Fort was the first to perforrh in France; the other has for its end to open the pelvis, and by removing the stone, to rid the organism of the cause of the morbid accidents; this is the nephrotomy which Rayer advised as early as 1846. Others have gone so far as to propose direct crushing of the stone in the kidney, and this is what our colleague Le Dentu did very suc- cessfully in one case. I can only indicate to you these operations, but as the successful cases are becoming more and more numerous, we must to-day regard this surgical inter- rerence as useful in a certain number of cases.* The * Medical literature has been enriched recently by a great number of observations of nephrectomy, both in France and in foreign lands. To the recent facts given by Le Dentu, who has practiced nephrectomy several times, and that of Pean, who, in a case of cancer, completely extirpated the kidney, we should add the observations of Rosenbach in Germany, and of Thornton, Thornburn, Palmer, in England, and of Vecchi and Wright in America. Rosenbach compiled sixty cases of extirpation of the kid- ney of which twenty eight were followed by death. Here is a resume of these different operations: — 104 — part of the surgeon has not consisted solely in pene- tratign the kidney to crush and extract calculi which have accumulated in the pelvis, but it has had for its end to remove this organ, whether in consequence of cancerous degeneration, or prolonged suppuration, or of simple ectopia; in the latter case, by a radical operation the patient is rid of the persistent pains which always accompany displacement of the kidney. But if surgical interference (at least till further ad- vances have been made) is to be counselled only as an extreme and desperate measure when it is a matter of ablation or incision of the kidney for calculous nephritis, you should have recourse to it, on the con- trary, when it is a case of propagation of the inflam- Twenty-nine times the operation was performed through the abdominal wall, and sixteen of these operations were fatal; thirty-six times it was performed by means of a lumbar incision and twelve were fatal. Seventeen times the operation was done for suppuration of the kidney or pelvis, with or without calculi, and seven of the cases died. Thirty times for tumors, and nine died. Nine times for hydronephrosis or cysts, and three died. Nine times for floating kidney, and two died. Five times for calculi and painful non-suppurating kidney, and two died. Five times for fistula of the ureter, and two died. Five times for adhesions with tumors, and two died. Twice for recent traumatism, and two got well. Once for tuberculosis, and one died. — i os — mation to the renal capsule, *. e., when you have to do with peri-nephritic abscess. These abscesses arise spontaneously, or they may be the consequence of renal sand. They manifest themselves by a train of symptoms that are character- istic, and in particular by the appearance of a fluctua- ting tumor in the region of .the kidney, and the usual constitutional disturbances which accompany exten- sive suppurations. Here surgical interference is nec- essary, and the free incision of these suppurating tumors to enable antiseptic washings to be performed, is the only curative treatment, and if I do not dwell longer on this point, it is because these operations belong rather to surgery than to medicine. Finally, there is another kind of tumor which may accompany urinary calculus, namely, hydro- nephrosis, that is to say, the cystic transformation of the kidney under the influence of the arrest of the urinary excretion. In this case, the urine first dis- tends the ureters, then the pelvis, then this distention affects the renal elements themselves, and there results a more or less voluminous pouch in which are found scarcely any traces of the renal parenchyma. These pouches may attain a great size and pre- sent all the symptoms of large abdominal cysts, par- ticularly those of the ovary. Confusion is sometimes almost inevitable, and the diagnosis can only be made when these cysts are punctured. It is quite possible then to find by analysis certain elements of the urine, particularly urea and urates. — 106 — For my part, I was witness of a case of this kind when I was clinical chief under Behier; it was a case of a woman who. was believed to be affected with an ovarian cyst; the tumor was tapped, and the aspect and odor of the liquid leading us to examine it care- fully, we then recognized the urinary origin of this sac. This-woman, moreover, made a good recoveiy. Finally, in certain very rare cases anuria has been observed, and in consequence thereof, uraemia, from obliteration of both ureters by calculi; recently my colleague and friend Tenesson has reported two cases of the kind. Here the medical treatment should consist in the use of diuretics on the one hand, and purgatives on the other, and it is necessary to vigor- ously combat both the anuria and the uraemic symp- toms which are produced by the obliteration of the ureters. Such are the accidents which may complicate lithiasis; I shall pass now to the study of the treat- ment of inflammations of the renal parenchyma, *. - • ^ Page. Diet in Bright's Disease....................... Itf- in Oxalic Gravel...................... go Digitalis in Bright's Disease............................ 153 as a Diuretic....... r-.. . ......................... 45 Diuretics.. .............. „ in Bright's Disease............................ I33 in Renal Lithiasis............................. 74 in Nephritic Colic............................ 06 in Oxaluria........................... g2 Doremas', Test of for Urea............................ 2? Dujardin-Beaumetz, his Classification of Diuretics....... 43 Elaterium in Bright's Disease.......................... 30 Elimination of Medicines by the Kidneys.............. 21 Ergot in Renal Hemorrhage. . ........................ IOo Ereigeron, Oil of in Renal Hemorrhage.................. 100 Esbach on Oxalic Acid as an Ingredient of Certain Foods, 80 Exercise in Treatment of Uric Lithiasis...............76, 78 Fennel as a Diuretic................................... 47 Flint, Dr. A......................................... 27 Fibrosis of Kidney.................................... TI8 Fonssagrives, his Classification of Diuretics............. 39 Fuchsine in Bright's Disease........................... 147 Furbringer on Oxalic Gravel........................... 7g Galen on Renal Lithiasis............................... 55 Galleic Acid in Bright's Disease......................... 140 Gautier On Elimination of Alkaloids by Kidneys....... 5 Gondret's Pomade.................................... 131 Graham, Studies of on Dialysis............-............. 42 Green, His Test for Urea.............................. 29 Gregg, His Metaphosphoric Test for Albumen........... 122 Gubler............................................... 22 His Classification of Diuretics................... 39 — 166 — Page. Haematuria, Divisions of............................... 99 Hamon, His Classification of Foods for Nephritis........ 154 Harlem Oil........................................... 86 Hemorrhages, Renal.................................. 97 Causes of......................... 98 Treatment of...................... 99 Hippocrates on Renal Lithiasis....................... 54 Humoral Theory of Bright's Disease.................... 126 Hydronephrosis................................... 91, 105 Hygiene in Bright's Disease.......................... 152 Hygienic Treatment of Uric Lithiasis................... 76 Hypobromate Test for Urea.......................... 16 Hypochlorite Test for Urea............................ 16 Infectious Nephritis................................... 160 Iodide of Potassium, Its Elimination by the Urine....... 35 Iris (Orris Root) as a Diuretic.......................... 47 Jaborandi in Bright's Disease.......................... 136 Jalap in Bright's Disease........................ ...... 139 Juniper as a Diuretic................................... 46 Kuss, His theory of Urination.......................... 4 Laure, His Classification of Diuretics................... 40 Leucomaines, Elimination of by the Kidney............. 47 Liebermeister on Sudation in Bright's Disease........... 158 Liquor Potassae in Uric Gravel......................... 68 Lithia salts in Uric Grayel........................... 69-70 Lithiasis, Alkaline..................................... 83 Urinary..................................... 53 Complications of............................ go Ludwig, His Theory of Urination...................... 4 Milk Diet in Bright's Disease........................... 143 Pyelitis.................................. I02 — 167 — Page. Millon's Test for Urea................................. r6 Mineral Waters as Diuretics......................... 45) 48 in Renal Lithiasis...................... 74 Morphine in Nephritic Colic.......................... g4 Murexide......................................... s6 Nephritis, Epithelial................................. u6 Parenchymatous....................... n6, 124 Interstitial..............................H6, 122 Infectious................................... 48 Nephrectomy......................................... I03 Nephrotomy.......................................... I03 Nitric Acid in Bright's Disease........................ 140 Nitrates as Diuretics................................... 4g Nitrogenous Foods, Their Influence on the Excretion of Urea.............................................. 13 Onions in Bright's Disease............................. 144 Oxalic Gravel...................................... 57, 78 Oxygen in Bright's Disease............................ 141 Oxygenated Water.................................... 51 Pareira Brava........................................ 48 Parietaria as a Diuretic............................... 46 Parsley............................................. 48 Perchloride of Iron in Bright's Disease....... ......... 140 Phosphates............................................ 19 in Urine................................... 34 Ammoniaco-Magnesian..................... 60 Pichi................................................ 86 Pilocarpine in Bright's Disease......................... 136 Potain on the bruit de galop............................. 119 Potassium Salts in Uric Gravel......................... 70 Ferrocyanide, its Elimination by the Urine ... 35 Ptomaines, Elimination of by the Kidneys............... ^7 — 168 — Page. Purgatives in Bright's Disease......................... 136 Pyelitis............................................... 101 Suppurative............................... 101, 102 Treatment of.................................. 102 Pyrola............................................... 48 Quinine, Elimination of by the Urine................... 35 Ralfe on Oxalic Gravel................................ 79 Revulsives in Bright's Disease........................ 130 Resins as Diuretics.................................... 50 Resorcin.............................................. 86 Roberts, Experiments of to Ascertain the Solvent action of Alkalies on Urinary Calculi........................ 67 Salicylic Acid, its Elimination by the Urine.............. 35 Sambucus as a Diuretic................................ 46 Sandal Oil in Haematuria.............................. 46 Sandalwood......................................... 85 Scoparius............................................. 47 See, his Classification of Diuretics...................... 39 Semmola............................................. 126 his Conclusions as to the Pathogeny of Bright's Disease................................. 127 his Antibrightic Liquid...................... 127 Senator on the Dietary of Bright's Disease.............. 156 Sinapisms in Bright's Disease.......................... 130 Soda Salts in Uric Gravel ............................. ji Spiraea Ulmaria....................................... 48 Squills as a Diuretic.................................. 47 in Bright's Disease ... ......................... I34 Steatosis of the Kidney................................ XI7 Stigmata of Maize...................................48-75 Sudation in Bright's Disease........................... Xc-j Tannin in Bright's Disease............................. I40 — 169 — Page. Tensor Diuretics...................................... 43 Toxicity of Medicines in Renal Diseases................ 37 Triticum Repens............>......................... 47 Trousseau on Alkaline Cachexia........................ 72 Tube Casts........................................... 113 Turpentines as Diuretics............................... 85 Uraemia............................................6, 138 Uric Gravel........................................55, 56 Causes of...............................61, 62 Urination, Theories of................................. 39 Urine.....................8, 9, 10, 11, 12,^13, 14, 15, 16, etc. Urobilin.............................................. 11 Urea................................................. n Urochlormetric Table.................................. 34 Uva Ursi............................................. 134 As a Diuretic................................ 46 Valerian as an Anuretic................................ 5* Voit, His Chemical Explanation of the Uric Diathesis--- 64. Water as a Diuretic................................... 45 Wettisch. His Theory of Urination..................... 4 Wood, His Classification of Diuretics................... 38 Xanthine.............,................................ 61 Yvon, Table of Urinary Composition................... 8 Ziemssen On the Diaphoretic Treatment of Bright's Dis- ease................................................ x58 « .& The Pepsin Question. facts we* £Cpsln do y°u Prescribe, and why? If you will examine the future JV^nt, you can have only one opinion as to pepsin in Dentin ,!Zll rs fully Presenting the claims we make for our scale investigaTe it * Sample of h> wiH be mailed to physicians who wish to strength T*!* °nly say here that in appearance, solubility, digestive nXn.iST-A P?rmanence, it is far superior, and admittedly so, to any pepsin hitherto introduced. ' VnAlardul search through the prescription file of a prominent New York pharmacist reveals the surprising fact that fully 75 per cent of «t£^nS °eg .ecti° specjfy when Prescribing pepsin, but simply order pure pepsin. Now they might as consistently order "solution of cocaine, without designating any particular strength. Pure Pepsin," as it is known commercially, is not a definite prin- ciple; neither has the Pharmacopoeia as yet established a standard of strength, and, consequently, every producer is a law unto himself It is obvious that digestive activity is the sole criterion of therapeutic value in preparations of the proteolytic ferment, and a physician is conse- quently enabled to predict with reasonable certainty the comparative effect that may be expected from the various pepsins found in the market. The following tabulated statement of the comparative quantities of the various pepsins that should be prescribed in order to accomplish the same purpose may, therefore, enable them to so write their prescriptions that the best shall be obtained at the lowest price. These figures are based upon each manufacturer's claim, without regard to the discrepancies which are known to exist; but when the fact be considered that our Pepsinum Purum in Lamellis, with a digestive power of one to 2000 is marketed at a price comparing favorably with that established for many of the inferior varieties, the economy of its employ- ment becomes patent. If it is desired to administer sufficient of the fer- ment to dissolve 1000 grs. of albumen, obviously, -J gr. of the aforemen- tioned pepsin will be sufficient. To derive the same therapeutic effect from one for which the manufacturer claims a power of 1200, ^ gr. will be necessary. A power of 1000, 1 gr.; a power of 900, 1^ gr.; a power of 700, if gr.; a power of 500, 2 grs.; a power 150, 6^ grs., while a power of 50 (which is the standard adopted by our Pharma- copoeia), 20 grs. will be necessary. PARKE, DAVIS & CO., Manufacturing Chemists, NEW YORK: Offices, 60 Maiden Lane. DETROIT. MICHIGAN Warehouse and Shipping Depot, 21 Liberty St. *' m^nj^K. Crude Drug Warehouse, 218 Pearl St. PHYSICIANS' LEISURE LIBRARY PRICE i PAPER, 25 CTS. PER COPY, $2.50 PER SET j CLOTH, 50 CTS. PER COPY, $5.00 PER SET. SERIES I. Inhalers. Inhalations and Innalants. By Beverley Robinson, M. D. The Use of Electricity in the Removal of Superfluous Hair and the Treatment of Various Facial Blemishes. By Geo. Henry Fox, M. D. New Medications. By Dujardin-Beaumetz, M. D. The Modern Treatment of Ear Diseases. By Samuel Sexton, M. D. Spinal Irritation. By William A. Hammond, M. D. The Modern Treatment of Eczema. By Henry G. Piffard, M. D. Antiseptic Midwifery. ., _ By Henry J. Garngues, M. D. On the Determination of the Necessity fof Wearing Glasses. „, _ By D7B. St. John Roosa, M. D. The Physiological,Pathological and Ther- apeutic Effects of Compressed Aira By Andrew H. Smith, M. D. GranularLidsandContagiousOPhthalmiti By W. F. Mittendorf, M. D. Practical Bacteriology. By Thomas E. Satterthwaite, M. D. Pregnancy, Parturition and the Puerperal State and their Complications. By Paul F. Munde\ M. D. SERIES II. The Diagnosis and Treatment of Haemor- rhoids. By Chas. B. Kelsey. M. D. Diseasesof the Heart. Vol.1. By Dujardin-Beaumetz, M. D. Diseasesof the Heart. Vol.11. By Dujardin-Beaumetz, M. D. The Modern Treatment of Diarrhoea and Dysentery. 'By A.'B. Palmer, M. D. Intestinal Diseasesof Children. By A. Jacobi, M. D. The Modern Treatment of Headaches. By Allan McLane Hamilton, M. D. The Modern Treatment of Pleurisy »nd Pneumonia. By G. M. Garland, M. D. How to Use the Laryngoscope. By an Eminent Laryngologist. Diseasesof the Male Urethra. By Kessenden N. Otis, M. D. The Disorders of Menstruation. By Edward W. Jenks, M. D. The Infectious Diseases. InSroU. By Karl Liebermeister. SERIES III. Abdominal Surgery. By Hal C. Wyman, M. D. Diseasesof the Liver. By Dujardin-Beaumetz, M.D. Hysteria and Epilepsy. By J. Leonard Corning, M. D. Diseases of the Kidney. By Dujardin-Beaumetz, M. D. The Theory and Practice of the Ophthal- moscope. By J. Herbert Claiborne, Jr., M. D. Modern Treatment of Bright's Disease. By Alfred L. Loomis, M. D. Clinical Lectures on Certain Diseases of Nervous System. By Prof, J. M. Charcot, M. D. The Radical Cure of Hernia. By Henry O. Marcy, A. M., M. D., L. L. D. The Treatment of Diseases of the Blad- der, Prostate and Urethra. By H. O. Walker, M. D. Dyspepsia. T3y Frank Woodbury, M. D. The Treatment of the Morphia Habit. By Krlenmeyer. The Etiologly, Diagnosis and Therapy of Tuberculosis By Prof. H. von Ziemssen. GEORGE S. DAVIS, PubUsher, O. IEo2C 470. 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