(compliments of the AUTHOR.] The Microscopical Proof of a Curative Process in Tuber- culosis; or the Reaction to Tuberculin Evidenced by Blood Changes Hitherto Unrecognized. AND My Latest Improved Binaural Stethoscope. BY CHARLES DENISON, A. M„ M. D. DENVER, COLORADO EX-PRESIDENT OF THE AMERICAN CLIMATOLOGICAL ASSOCIATION. EMERITUS PROFESSOR OF DISEASES OF THE CHEST AND OF CLIMATOLOGY MEDICAL DEPARTMENT, UNIVERSITY OF DENVER. AUTHOR OF "THE ROCKY MOUNTAIN HEALTH RESORTS," "THE CLIMATES OF THE UNITED STATES IN COLORS," "EXERCISE AND FOOD FOR PUL- MONARY INVALIDS," ETC. Reprinted from Proceedings of the Twenty-Sixth .Annual Meeting, of. the Colorado State Medical Society. The Microscopical Proof of a Curative Process in Tuberculosis; or the Reaction to Tuberculin Evidenced by Blood Changes Hitherto Unrec- ognized. There is urgent need of a gauge to go with treatments claimed to be curative in consumption, by which their relative merits may be determined. There is no lack of "cures," so- called. "The woods are full of them;" but the limitation of the curative process common to most of them has never been accurately determined. Thus far climate-and the preferable climate is on this eastern Rocky mountain slope-has proved to be first in the list of remedial means, however its curative power is in- creased by other agencies. The latest claim to curative fame-aseptolin-is by no means an exception to this estimate. The treatment has some merit in it. However, the profession will grant much of the credit to the Frenchman, Declat, who many years ago put for- ward the hypodermatic use of phenol, and to Dr. Louis Wald- stein, of New York, who in Berlin made prominent the similar use of pilocarpine, as well as to Dr. Cyrus Edson who, by com- bining them, has lately "boomed" the new remedy-aseptolin -into extended use. Yet the effects have to be acknowledged as considerably limited and not so different in kind as we would wish, from those produced by the Shurly and Gibbs method, with chloride of gold and iodine, the effort to saturate the system with creosote, etc. 2 Tuberculin, and antipthisin (Kleb's), which is considered by some (Trudeau and Baldwin) only a modilication of it, has not yet impressed the medical profession with its great worth as a means of treatment, for reasons the profession are prob- ably responsible for, though as a diagnostic of tuberculosis its position is well recognized by veterinarians. It is, therefore, very gratifying to have the hope revived that there may be found a trustworthy means of comparing and judging these curative methods through the microscopic examination of the blood. Perhaps the members of this society have in mind the resolution I had the honor to propose two years ago, offering a reward or prize of $100 for the best essay presented a year hence upon this subject. To be sure the pecuniary induce- ment offered was too small, and that may have been one of the reasons why the task was not undertaken. Yet the honor, if successful in such a magnificent undertaking, was then, and is still a sufficient inducement to excite the energies of any one able to accomplish the task. The purpose is to diagnose tuber- culosis and differentiate its varieties by the microscopic examina- tion of the blood alone, without the patient being seen. You have heard Dr. A. M. Holmes' paper, and are, 1 trust, prepared to join in encouraging him to succeed in this matter. I hope the pecuniary consideration may be renewed by this society and another year's opportunity be given Dr. Holmes, or any one else who will enter the lists with as original and conscientious work as is evidenced in his paper. The honor is one we would all feel proud to have conferred upon a Colo- rado physician, and it seems that Dr. Holmes is very near the goal. It was to apply his method of staining and blood examina- tion in order to determine the cell changes induced by the re- action to tuberculin, that I asked Dr. Holmes to study with me two of my cases some ten weeks ago. The results are new. and I am gratified to present them to you in so clear a form, con sidering the short time the study has been in progress. Much credit is due Dr. Holmes, for I am unaware that just this method of study and comparison has been carried out by any 3 one else. A short history will enable us to comprehend case one, which was primarily a pulmonary, and afterward a surg- ical tuberculosis affection. Case 1-Male, age 38, first seen July 26, 1895; a banker, married eight years, just arrived from Vermont. His mother, whom the patient much resembled, died of consumption. This patient had la grippe two years previously, followed by cough, and last winter another attack, when he had night sweats. Weight about 150; not decreased, because of good living and care; only slight effect of elevation; cough not severe; expecto- ration whitish, about one ounce in twenty-four hours and con- taining tubercle bacilli, three to five to field, streptococci and diplococci. Some infiltration and dullness at left apex, and very slight impairment of respiratory sound on right side. Diag- nosis-Fibro-tuberculosis, first stage. Treatment-To use the inhaler, because of the bronchitis and mixed infection, and to go into the mountains. September 6-Has been at Idaho Springs and improved somewhat. Spirometrical record has increased from 205 to 225 cubic inches, and manometer record from 95 to 110 M. M. December 19-Commenced tuberculin (Koch's) September 9, with ultimately gradually increasing intervals between the injections. The reactions were light and only occurred after a few of the smaller doses. About 60 mgrs. as a maximum dose was reached. The sputum cleared up (the germs disap- pearing), and finally ceased altogether. April 14, 1896-Up to February 7, the lung condition con- tinued most favorable, but the tuberculosis had not been wholly eliminated from his blood, for a small abcess then came underneath the scalp above the forehead, the pus from which was found to contain tubercle bacilli; also, perhaps follow- ing a strain of right arm and much pain which kept him awake nights, an abcess formed and infiltrated the tissues be- low the right elbow joint. These conditions both improved un- der drainage, the renewal of tuberculin and the administration of hypophosphites with hydriodic acid. The scalp abscess has healed entirely, but the trouble in the arm evidently comes from tuberculous necrosis and will necessitate an operation. 4 April 15, 1896-Dr. J. J. Powers operated on the right elbow and we found, as we expected, necrosis of the ulnar (both front and back sides of it near the end), the joint, per- haps, just escaping. A conservative plan was decided upon-to rather freely expose and scrape the diseased bone, after which the wounds were thoroughly packed with iodoform gauze. June 13-The dressings were continued until the wounds had healed by granulations from the bottom. During the time of and preceding the operation on the elbow for three or four weeks, no tuberculin was given, and it was during this period when the necrosis of the ulner was well under way, that the first blood examination-namely, that of April 11-was made by Dr. Holmes, indicating, as he stated, a serious inflammatory state of the blood and some bone affection-i. e., "an excess of bone marrow or spleen activity." The tuberculin was con- tinued and given about every fourth day, from about the first of May to date, in gradually increasing doses, from 20 to 70 miligrams for a maximum dose, till there was finally no reac- tion to speak of to those larger doses. This was during the time the other four blood examinations were made, the in- crease of the young or new cells, the small lymphocytes, being in exact hormony with a decided improvement in the patient's condition in every way-in weight, appetite, strength, feelings, mobility of the affected joint and ability to exercise. It is hoped the apparent, though perhaps only approximate, immu- nity reached in this case will prove to be of a permanent nature, as has been the case in quite a number of patients treated from one to five years ago. Of course these were se- lected with all the care and precaution possible as suitable for this method, for none others, in my judgment, should ever be given tuberculin except for diagnostic purposes. The progress of the above case, and of the one yet to be described, together with the numerical changes in the proportion of the various cells of the blood, is shown in the accompanying table which Dr. Holmes has kindly prepared for me. To this is appended about the normal proportion of the different cells according to Neudorf er, of Vienna, for the purpose of comparison. 5 Small Lymphocytes. Large Lymphocytes. Neutrophyle Leucocytes. Eosinophile. Myelocytes. REMARKS. About the normal 26 8 65 I O Case I. April ii. Necrosis forming 6 21 72 5 I Average of 500. May 6. 2^ hours after tuber- culin injection . 9 17 72 2 O I i il May 8. 10:30 a. m. , just before an injection .. 20 66 3 O ii ii May 8. 7:30 p. M., 8j^ hours after an injection 18 l6 64 2 O I i a May 19 7 days after an injec- tion 32 13 53 O • 1 ii Case II. Note increase of small lymphocytes. April 13. 5 p. m., before treat- ment 7 19 72 I I April 14. 5 hours after injec- tion, 4:30 P. M 16 IO 73 s I April 15. 30 hours after injec- tion, 5:30 P. M 16 l6 66 I I May 16. 7 hours after injec- tion, 5 P. M 21 7 72 O O Extreme retrograde metamorphosis. June i». Third day after injec- tion, IO A. M 9 13 77 O I Evidence of pus for- mation and retro- grade metamor- phosis external. Case III. About June 8, before test with tuberculin ; 8 21 70 I O Evidencing tubercu- losis. June 17, next dav after second reaction to tuberculin 17 13 70 1 O Increase of small lymphocytes and tissue metamor- phosis. RECORD OF BLOOD EXAMINATIONS. 6 Case 2-Miss , age 22, first examined by me Febru- ary 17, 1896. Both the patient's sisters are possibly tubercu- lous, mother frail, and mother's two brothers and one sister died of consumption. Previous to coming to Colorado from Maine, which was about seven years ago, she had neuralgia, some cough and fever, was weak and sick, and had yellow ex- pectoration at age of sixteen. Greatly improved, and cata- menia became regular in Colorado. She ceased expectorating after one month. When eighteen years old, glands in both axillae swelled; these disappeared in three years. But before that, namely two years ago, the hard lumps came on the right side of the neck, and one year ago on the left side. There must be as many as twenty on the right side, reaching from the ear to the middle third of the clavicle and nearly as far down on the left side. Those on the right are the largest, causing marked deformity, and two of them are commencing to sup- purate. There is little or no expectoration, some slight daily temperature rise, spirometrical record 130 cubic inches, and manometer record 60 M. M.; weight before coming. 105. now 123 pounds; expansion, 29 1-2 and 31 inches, a little greater deficiency on the right than on the left side. Remnants of en- larged glands noted in both axillae, some depression in right infra clavicular space. Physical examination revealed no rales or breaking down of lung tissue, but broncho vesicular breath-sounds, some dullness and exaggerated voice at both apices, front and rear, with prolonged expiration in right infra- clavicular space. The diagnosis was strumous phthisis, so- called, which was proved immediately afterward to be tuber- culous by the tuberculin test. The local reaction was positive, known by the high-pitched broncho-vesicular exaggeration in the left interscapular space. This was noted after the 6 mgr. tuberculin dose, and afterward it was quite general over the lungs. The glands in the neck also began to get harder, and there was temperature reaction which seemed to become ex- cessive, showing extreme susceptibility. The test was stopped to prepare for the enucleation of the glands, and thus get rid of so much tuberculous tissue. This operation was per- formed by Dr. J. J. Powers, assisted by Drs. O'Connor. Peder- sen and myself, April 29, and some seventeen to twenty glands 7 were nicely enucleated. It was before and after this opera- tion that the blood examinations shown in the table were made, in connection with very small and infrequent doses of tuberculin. The value of these examinations made by Dr. Holmes was manifest, showing the coincidence of an abnormal susceptibil- ity 'and the excessive tissue metamorphosis which was going on. Notwithstanding other signs of improvement in this patient's condition, this discovery contra-indicated the pushing of such treatment with so much tuberculous tissue to be gotten rid of, and the moderate use of antiphthisin (Klebs) was sub- stituted, with mild inunctions of the oleate of mercury and the internal administration of syrup of hypophosphites and of hydriodic acid. This is preparatory to the extirpation in the near future of the rest of the glands, on the left side. This ob- stinate diseased condition is of the more interest because of its persistence and the profound infection of the system, as well as because it shows that the glandular enlargements we have always thought to be scrofulous, are profoundly tuberculous, though, as in this case, no bacilli are found in the glands re- moved. Note-September 8, 1896. These two cases have each continued to recover since these reports were made. Both show increase in weight, etc. In the second case, the glands on left side of the neck and in right axilla have shrunken so much that the patient requests a postponement of any further opera- tion, believing she will recover without it. This verifies a statement I have previously made, based upon our inability to find the bacilli tuberculosis in tissues evi- dently tuberculous, as in adenoid growths in the region of the third tonsil in patients afterward dying of tuberculosis- namely, that there is a pre-tuberculous state, of which some evidence besides the bacillus of tubercle must be found. Whether that evidence is to be found, as for a long time I have hoped it would be, in the proper microscopic examination of the blood, or as I believe it does exist in the tuberculin test, there is no doubt in my own mind that the two methods will go hand in hand and verify or check each other, just as surely as do the control tests of the assayers in our sampling works. 8 A beautiful illustration of the value of both these tests is now given us in another of my cases whose blood has just lately been examined by Dr. Holmes. (See Case HI.) I refer to the case he describes in which I could find no bacilli in the sputum, and had diagnosed bronchitis and hydro-nephrosis and possibly latent tuberculosis. But Dr. Holmes was sure from the morphological appearance of the blood that the case jvas tuberculous, he knowing nothing of the kidney complication. I have since tested this patient with tuberculin and obtained a distinct reaction, proving Dr. Holmes' diagnosis to be correct. The morphological state of the blood indicates an enlarged spleen and tuberculous kidney. At the same time a diagnosis of tuberculous adenoma of the kidney, complicating hydro- or pylo-nephrosis, and perhaps calculus, seems to be warranted by the gross appearance of this tumor. It reaches from the spine around to within three inches of the navel and from be- low the sixth rib in front to within two inches of the crest of the ileum, with oval borders. This conclusion is supported by the history of hemorrhages and the discharge of pus in the urine, and the fact that he has lived as a miner in high alti- tudes for thirty years, excepting short sojourns in the East, during one of which, at the world's fair in Chicago, his prin- cipal attack occurred. Note. September 8. This case has also improved under the tuberculin injection; general condition better and tumor lessened in size. What will be done with this tumor other than to con- tinue the present favorable course of tuberculin is not yet de- termined. The patient is, however, present, and suggestions will be gladly received. The tumor seems to have commenced to decrease in size since the beginning of the tuberculin test. I have given this patient an injection this forenoon that you might now the better detect the reaction sound, which will be found in the left infrascapular space. As to tuberculin: I was much impressed by Dr. Hance's statement in his late paper on the treatment of pulmonary tuberculosis (Medical Record. May 2, 1896). which verifies my own experience, and which I will quote in closing: "The writer recalls at least four patients who could not continue the use of tuberculin, but subsequently arrested their 9 disease process under proper climatic treatment. After the continuous use of tuberculin, or its modifications, extending over a period of nearly five years, he is of the opinion that patients who are "relatively cured" by the use of tuberculin and climatic treatment have stronger resisting powers against subsequent infection than those who have secured the same results by climatic treatment alone. In other words, their cure (if one may use such a term) is much more firm and lasting than in other cases.' Dr. Denison moved that the Committee of Award formed last year to confer a prize of $100 upon the author of the best essay on "Diagnosis of Tuberculosis by Microscopical Examin- ation of the Blood" be enlarged and that Drs. Chas. Powers and E. R. Axtell be added for another year. Motion seconded by Dr. Grant and carried. The Committee of Award is composed of Drs. C. Denison, Chairman; S. E. Solly, H. A. Lemen, C. A. Powers and E. R. Axtell, and communications will be gladly received by the Chairman at 823 Fourteenth street, Denver, Colorado. 10 My Latest Improved Binaural Stethoscope. The results of experimenting with the stethoscope and the study of the laws of acoustics have led to some changes in the instrument called after my name. At the same time the com- petition among dealers has led to harmful cheapening of my original design, as made by Tiemann & Company, so that in some instances I cannot recognize my own child in the produc- tion I am supposed to father. I, therefore, determined to accentuate the points proved essential, make needed corrections, and have the new moulds controlled so as to keep the instrument up to a desirable stand- ard of excellence. With a few minor changes in the next lot to be made this desirable end will be reached. The large calibre of the main tube, gradually decreasing as in deaf persons' speaking tubes down to the size appropriate for the ear ending, has been proved to be an essential feature in the correct stethoscope. As with light, so with sound, the angle of incidence and reflection are equal, and the gathered sounds are not only transmitted in the substance of which the instrument is constructed, but in the gradually concentrated column of air which the tubes contain. The even division of this transmitted sound, so that the delivery is alike to both ears, has been proved by experience to be preferable to any other method. The substances of which the parts are con- structed are most important considerations, which seem to be wholly unrecognized in the long, small, soft rubber tubes which are the chief features of some cheap and handy affairs. If steel wire is imbedded in the soft rubber of the flexible tubes, and the size of these conveyors kept moderately large, with smooth surfaces inside, the best effects are produced, as in the instrument here illustrated. This is shown by a test which 11 is a good one for all stethoscopes, for it is really the clearness, distinctness, and naturalness of the transmission which should establish a given instrument as superior, rather than any con- sideration of mere convenience of form for carrying, or of size as to looks. Here is the test: Place a watch on the table and cover it with the palm of the hand, while with the other you press the THE DENVER SURGICAL INST. CO. bell of the stethoscope firmly on the dorsal surface. If the two bells, of instruments being compared, cannot equally be im- bedded in the flesh so as to equally exclude outside air, then put the back of the hand on the watch and press the bells in the palm. The best effects under such conditions determine the best instrument for cardiac and lung examinations, especially the former. The conditions are very similar to those existing 12 in the test named as to the transmission of the sound through bone and flesh combined, with this difference, that in the test given, the table-top underneath the watch gives a drum-like reverberation and exaggeration of the watch-ticks, which ful- fills the requirements of a definite as well as a delicate test. Thus a weak ticking watch will have the movements of its ma- chinery detected by one stethoscope of which no sound at all is audible by another. And here the fact is made evident that a proportion of listeners-and I suspect no small proportion, either-are just enough defective in hearing to have to depend almost wholly on the sound transmitting substance of which their instruments are made. To such the large sized tubes, with the imbedded steel wire coiled in the soft rubber, are great helps, while the long, soft tubes, which allow of sound transmission only through the air columns within, are of no use whatever. Make every allowance possible for those few whose hear- ing may be acute enough to hear passably well with the latter, there yet remains a majority to whom the former gives clearer and more satisfactorily transmitted sounds. This sound trans- mission is intensified by pretty firm pressure of the ear tips into the external auditory canals, and this desired pressure is af- forded in the adjustable control attached to the purposely made stiff spring between the two arms. Everyone can thus limit the amount of pressure he can stand by his own comfort. The direction of the auditory canals with reference to the side of the head is more constant than the size, and this latter varia- tion has seemed to make it necessary to divide the ear-tips into three regular sizes, and enable physicians to have a choice. These I have made interchangeable on the uniform screw ends of the tubes. The medium sized pair of ear ends will fit the majority, w'hile of the remainder, more will choose the smallest than the largest size. This, my latest invention, is found to be of great advan- tage. The direction of the ear ends may be varied if required by heating in hot water and binding the tubes down; but as- suming that the arms of the stethoscope are usually held close to or under the sides of the jaw, the direction of the ear-tips 13 should then be inwards and slightly forward and upward. This is the regular curve to which these arms are moulded. The method of joining the tubes, and of inserting the bells in the main tube, is definitely settled as best by the insertion of slightly conical ends into the openings. The bell endings are four in number, and each variety has its distinct purpose. The end of the main tube is rounded out and made slightly flaring at its extreme edge to form the smallest bell suitable for examining children's chests and for differentiating heart lesions, etc. The ordinary sized bell is also made flaring at its border so as to give a good impinging surface against the chest wall, as thus sound transmission is aided; and the soft rubber bell is made thin and of size to project over the edge of the medium sized bell the fourth of an inch or less, thus closing all uneven places on the chest wall in examining much emaciated per- sons. StethoscOpic percussion, for which I have devised this large bell-diameter three inches-is what I make a particular point of in outlining cavities and detecting softening, and I very much wish the profession practiced it more universally than they do. It is a nice evidence of those serious states of lung tissue, often so definite and assuring in its import, that I may be excused, I hope, for describing it more minutely in this connection. The object is to get a concussion of air in an open space in the lung, or a succussion when such a caviaty is partly bathed or filled with fluid, so that the impression is conveyed along the bronchial tract and out of the patient's open mouth. Then it is caught in the large bell and conveyed to the listener's ears. Of course this must be during expiration, because then the chest wall is more relaxed and impressible, and the sounds are helped along by the outward-bound current of air. The physi- cian sits or stands in front of the patient, while the assistant or the patient himself holds the large bell in position about an inch in front of his open mouth. Then, during long, full ex- pirations, the examiner makes forcible or light percussion as indications require, to find deep or superficial- evidence of exca- vation. There is a "cracked metal" and hollow sound over dry 14 hollow spaces, and a changed succussion sound over moist cav- ities, which is usually quite definite, and which can be outlined on the surface of the chest-with an easy marking pencil-in a way which is very definite and gratifying. In fact, there is no diagnosis that I know of equal to it in determining the lim- its and size of an excavation out of sight, even as when it lies underneath a shoulder blade. In corroborative evidence of the indications furnished by other signs, and certainty of con- clusions, as to the limits of lung destruction reached, there is no sign more important than this one rightly interpreted. In the estimation of advanced tuberculosis in the lungs it is very important. I speak with the more emphasis on this point, be- cause I know I have met with many cases of softening already begun, and in others even of excavation established, which had not been previously detected, solely, I think, because this stethoscopic percussion had not been tried. The stethoscope here presented and illustrated has given me much satisfaction, as certain defects or changes, incident to age, make me more dependent upon such an instrument. I hope you will agree with me that even if it is not exactly per- fect, it is nearly so.