dfewll Htmraitg ptag THE GIFT OF ..^.J^A^ft(...VlOJUUS5JUfiR. A2.s.»\a.i ga.JB..[.u. 6896-2 arV1 8895 Corne " ""Orally Library olin.anx 3 1924 031 268 380 Cornell University Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924031268380 lEaaagB on Eannratnnj Itagnoata fax % (Snteral Jlrartttumrc ESSAYS ON LA BORA TOR Y DIAGNOSIS —FOR THE— GENERAL PRACTITIONER BY HENRY R. HARROWER, M. D. Professor of Clinical Diagnosis, Bennett Medical College (Medical Department Loyola University); Editor, "The American Journal of Physiologic Therapeutics", Member, American Medical Association, American Association for Medical Research, Tri-State Medical Society, Etc., Etc. CHICAGO NEW MEDICINE PUBLISHING CO. 1911 -rni — H - \0-\^ — - - Copyright 1911 BY HENRY R. HARROWER.^M. D. ENTIRED AT STATIONERS HALL, LONDON ALL RIGHTS ..RESERVED QJa iffin lit TABLE OF CONTENTS. PAGE Preface 13 Introduction — By W. F. Waugh, A.M., M.D 17 Chapter I. — The Laboratory as a Means of Pro- moting Professional Proficiency 23 (Medical World, November, 1908.) Chapter II. — The Importance of Laboratory Methods 29 (Chicago Clinic, June, 1909.) Chapter III. — Success in the Treatment of Chronic Disease 35 (American Medicine, February, 1910.) Chapter IV. — An Important Element of Success in the Treatment of Chronic Diseases 47 (Medical Standard, October, 1909.) Chapter V. — Mysticism and Medicine 57 (Medical Standard, March, 1910.) Chapter VI. — The Advantages of the Urine Ex- amination 65 (Milwaukee Medical Journal, December, 1909.) Chapter VII. — Prophylactic Laboratory Work. ... 73 (Medical Standard, June, 1910.) Chapter VIII. — Routine Urine Examinations 77 (New York Medical Journal, Feb. 27, 1909.) 10 Table of Contents PAGE Chapter IX. — A New Instrument for the Estima- tion of the Urinary Acidity 83 (New York Medical Journal, Jan. 2, 1909.) Chapter X. — A Study of the Urinary Acidity and Its Relations 89 (Medical Record, June 5, 1909.) Chapter XI. — Acidemia and Autointoxication 109 (American Medicine, January, 1909.) Chapter XII. — Acidemia: Systemic Hypo- Alka- linity 115 (Medical Brief, August, 1910.) Chapter XIII. — The Relations and Clinical Sig- nificance of the Urinary Acidity 127 (Illinois Medical Journal, October, 1910.) Chapter XIV. — The Urinary Ammonia in Routine Work 141 (Medical Council, January, 1911.) Chapter XV. — The Collection of the Urinary Specimen 153 (Medical Standard, September, 1909.) Chapter XVI.— Low Total Solids : Its Treatment 161 (General Practitioner, December, 1910.) Chapter XVII. — What the Urine Report Means.. 169 (Clinical Medicine, August, 1909.) Chapter XVIII. — The Therapeutic Indications of the Urinalysis 187 (Clinical Medicine, October, 1909.) Table of Contents 11 PAGE Chapter XIX. — Laboratory Help in Tuberculosis. . 197 {Clinical Medicine, July, 1909.) Chapter XX. — The Urine in Tuberculosis 205 {Medical Standard, April, 1910.) Chapter XXI. — Conclusive Researches in Meta- bolism 215 {Lancet-Clinic, Nov. 12, 1910.) Chapter XXII. — Indican from the Standpoint of the General Practitioner 225 {American Medicine, December, 1910.) Chapter XXIII. — Indicanuria and Enteroptosis . . . 241 {Physiologic Therapeutics, May, 1910.) Chapter XXIV. — The Value of the Urinalysis in Dermatology 249 {American Journal of Dermatology, May, 1909.) Chapter XXV. — The Life Insurance "Urine Exam- ination" — A Farce 257 {American Medicine, October, 1909.) Chapter XXVI. — Metabolism and Mouth-Disease. 265 {The Journal of the Amer. Med. Ass'n, Oct. 1, 1910.) Chapter XXVII. — The Importance of the Clinical Laboratory in Surgery 273 {American Journal of Surgery, October, 1910.) Chapter XXVIII.— The Twenty-Five-Dollar Office Laboratory 283 {Medical World, March, 1911.) PREFACE. "There is nothing new under the sun," nor is there anything new in this book, but several important facts which seem to have been somewhat overlooked in the past are reiterated here because, as the venerable physi- cian and educator, A. Jacobi, has well said: "Simple truths in practical medicine do not merely bear repetition — they require it." To find laboratory work done by the general prac- titioner, is the exception rather than the rule. To find any physician who is in the habit of making a thorough investigation of the metabolic functions of every patient seeking his aid, is almost impossible. He does not see the need for it and "the patient won't stand for it." And yet every disease either affects, or is affected by, the way in which the vital interchanges take place. I have tried, in the papers which are reprinted here, to accomplish three things : First, to stimulate a greater interest in the actual need for clinical laboratory work by the physician in his own office; second, to simplify certain phases of this work; third, to cause, as best I can, a better understanding of the actual laboratory findings, and to make the therapeutic ends to which they point as clear and plain as possible. The attempt has been, on the whole, to lead rather than to teach. One unfortunate circumstance which has often 14 Essays on Laboratory Diagnosis impressed me is that when an article has once appeared in print, it is read, appreciated, perhaps, and either laid aside or destroyed. Rarely is it at hand for convenient reference. From correspondence with hundreds of physicians in various parts of this country and abroad, I have been impressed that the majority of these articles are of some real help. This is encouraging. Hundreds of requests for reprints had to be denied sim- ply because they were not at hand. Hundreds more re- ceived reprints when I had them to give. But none received more than two or three reprints and many re- quests have finally caused me to venture the publication of this collection. No attempt has been made to make this either a hand-book or a text-book. The papers are republished with little or no changes. I am conscious of many short- comings, the principal among them being frequent rep- etition. I hope these will be overlooked. One corre- spondent explained away this excuse of mine for post- poning publication of the book by saying: "You know the truth can stand a whole lot of repetition." It is to be hoped that this little effort may continue to serve as a stimulus to practice more thorough and, consequently, more successful medicine. Park Ridge, Illinois. INTRODUCTION. By William Francis Waugh, A. M., M. D., Dean and Professor of Therapeutics, Bennett Medical College, Chicago; Medical Department Loyola University; Editor "American Journal of Clinical Medicine," etc. INTRODUCTION. This little book is a praiseworthy attempt to stimu- late a greater interest on the part of the average physi- cian in the importance of utilizing clinical laboratory methods in his daily routine. Too many physicians are prone, even in these days of enlightenment, to consider that the urine examination is indicated only in suspected renal or bladder diseases. The importance of the urinary findings as a guide to the resistant powers of the body is all too frequently overlooked. Two generations ago disease was considered solely in its clinical aspect, and the aberrations from healthy func- tional activity formed the chief concern of the physician. As the study of pathologic anatomy progressed the basis of our conceptions of disease changed. We had been familiar with certain diseases as characterized by well- defined symptom-groups, and against these we had di- rected our therapeutics with considerable success. Dis- ease and its treatment were thus linked by observations extending over many centuries, with constant improve- ment as old superstition was replaced by modern sci- ence, old error eliminated by more precise methods of observation and reasoning. The new knowledge dimmed this picture, and replaced it by one in which the symp- toms of the living patient were obscured by the lesions discovered in the body of the dead. Too often it was 18 Essays on Laboratory Diagnosis forgotten that we were then dealing with the end- results of the pathologic processes, with the ashes of a burned-out fire. No disease presents structural lesions at the start. All begin with disorders of the vital functions which, proceeding unchecked, result in such irritation some- where as to invoke organic disease with destructive alter- ations. Since these are very often beyond the reach of curative treatment, it is up to us to recognize these affections while as yet in the early stages of functional derangement, when a cure may be effected. This brings the physician back from the laboratory to the sick-room ; from the study of completed pathologic processes; from dead anatomy, to that of disordered vital function in the living body. It emphasizes the value of the proposi- tion that our best work is to be done before the patient is taken down with sickness. It urges the supreme value of preventive medicine as applied to the individ- ual. The value of the quantitative examination of the urine as a means of judging the state of the metabolism can only be ignored by him who has not learned the inestimable aid it affords to a correct diagnosis of the state of the physiologic functions. The diagnosis of disordered functions is of far greater therapeutic importance — at least as far as results are concerned — than the corroboration of the presence of some suspected organic disease. In the former, infor- mation is gained which can be used to great advantage; whereas, in the latter a belief is only strengthened and Introduction 19 the possibilities of successful end-results dimmed. The times demand that the physician must earn his pay. He must be useful. He must be able to cope with disease or step aside for the other man. Diagnosis is but a preliminary, and if it does not point the way to effective treatment, it does not meet the needs of the situation. The science of medicine is supplemented by the art. Considerable stress has been laid by Doctor Har- rower upon the urinary acidity as a point of importance in diagnosis, and this is as it should be. The alkalinity of the blood is a factor of intense interest, since upon its variations the whole of the functions of the vital fluid depend. For these reasons I commend this useful little book to those for whom it has been prepared. Chicago, October, 1910. THE LABORATORY AS A MEANS OF PRO- MOTING PROFESSIONAL EFFICIENCY. Reprinted from THE MEDICAL WORLD, Philadelphia, November, 1908. CHAPTER I. THE LABORATORY AS A MEANS OF PRO- MOTING PROFESSIONAL EFFICIENCY. Every live medical man is continually on the look- out for something that will increase his efficiency. The crowded condition of the profession and the continual stream of new men from the many medical schools make it imperative for the progressive practitioner to increase his efficiency. He must get results. The periodical trip to Chicago, New York, or even to Europe for post-graduate study, the purchase of the latest and best medical books, the regular perusal of three or four good, live medical journals, and the attendance at the local medical society are all greatly conducive to better practice; but the continued use of the clinical laboratory will do more, perhaps, than any one thing to make for thorough and accurate work. With the majority of practitioners the sins of omis- sion are usually far greater than the sins of commission ; in other words, the average doctor of today errs more on the side of laxness than from the exhibition of an overplus of effort or enthusiasm in his attempts at care- ful diagnosis. Many a patient goes from one physician to another, at each change leaving his previous medical adviser slightly richer in dollars, but with a marked diminution of reputation. This is most unfortunate, for a reputa- tion cannot be measured in mere currency. It is well known that the American public is gullible 24 Essays on Laboratory Diagnosis in the extreme — is easily duped. The huge sales of the hundreds of patent medicines and the success of the ever-increasing army of advertising quacks both testify to this. Yet it would seem a shame to say that many — so many — of the ethical, apparently sincere and consci- entious medical men are today doing nothing so very far removed from the deeds of the nostrum vendor or the charlatan. In these days of medical enlightenment, the physician still exists whose clinical examination con- sists of nothing more than the few perfunctory ques- tions, inspection of the tongue, and a fleeting touch of the pulse; but who, because of the influence gained by years of practice, still manages to make a more or less decent living. Let us make this a personal matter. Doctor, when Mrs. A. came into your office the other day complaining of that "tired feeling," and told of the headache, the pain in the side and back, the lack of energy, and the many other symptoms that we are constantly called upon to meet, did you ask for a specimen of the urine? Did you get a full 24-hour specimen and examine it carefully, finding out not only the specific gravity and whether albumin or sugar were present, but the acidity, urea, phosphates, indican, and so forth? Would not this, perhaps, have given you a little more light on the prob- lem? And when Mr. B. came to you with his story about his stomach, and how Dr. X. and Dr. Y. and even old Dr. Z. had treated him successively (but not suc- cessfully), did you emphasize the importance of a thor- ough examination, and a test-breakfast? Or did you Promoting Professional Proficiency 25 just tell him that "fried foods are not so easily digested,'' or "rapid eating is hard on the stomach," give him some papayans or your favorite digestive what-not, and send him on his way to the next doctor to whom he might be recommended when your temporary relief ended? "But," you will say, "the people won't permit such examinations. You couldn't get them to pay for lab- oratory service." That may be; but you can, just the same, make it your definite routine practice with every case that comes to you for attention. It is true that your fees for clinical laboratory work may not all be paid, but the proportion will not be so very different from that of your other collections, some of which must, in due time, be marked down under "profit and loss." Or, again, the well-known excuse, "Oh! I haven't time to bother with that kind of work. I'm too busy." Very true; but haven't you time to spend by the bed- side of the dangerously sick one, watching, working, and fighting hard, the crisis being near? You say, "Of course." Well, then, is not the treatment of the chronic and semi-chronic diseases, the lingering, nagging troubles that are all too common, as difficult in the end as the care of an acute case near the crisis? The practice of medicine is no easy matter. It may be very true that your well-stocked library and literature files can give you interesting and valuable information regarding therapeutics, but nothing save your own ef- forts will enable you to make the all-important diag- nosis. If the highly trained hospital expert with access to 26 Essays on Laboratory Diagnosis so many interesting and complicated cases has to rely on laboratory assistance in his diagnostic work, must not such work be needful in your own practice? To- day's medical literature is simply teeming with articles demonstrating absolutely that accurate clinical methods are not only needful, but imperative. Can you afford to be behind the times ? Is not the reputation of being thorough and consci- entious well worth the time the few laboratory examina- tions may entail? Even though you may not be at all sure of a fee, is it not of sufficient value to you to know, and to know that you know? The small clinical laboratory has much in its favor; and I am thoroughly convinced that the money spent on equipment and the much-begrudged time spent at the actual work is the best investment that could be made. Osier has well said: "A room fitted as a small labora- tory, with the necessary chemicals and microscope, will prove a better investment in the long run than a static machine or a new-fangled air-pressure spray apparatus." The laboratory should be the backbone of the prac- tice of the general practitioner. It should occupy a place ranking equally with the other methods of precision in clinical diagnosis. It will bring you in contact with many persons whom you might otherwise never have met, and will enable you to see through cases that have baffled others. It will make for you a reputation for thoroughness and carefulness that cannot be compared in value with the time and money spent. The time spent in laboratory work will pay big dividends. II. THE IMPORTANCE OF LABORATORY METHODS. Reprinted from THE CHICAGO CLINIC, Chicago, June, 1909. CHAPTER II. THE IMPORTANCE OF LABORATORY METHODS. Laboratory work as an adjunct measure in both the diagnosis and treatment of disease is an essential, if success is expected in the practice of medicine. The laboratory alone is not infallible, supplanting the well- tried methods of precision and skill of the trained eye, ear, or finger tip of the diagnostician; but no matter how skilled the man, nor how valuable the methods, without laboratory aid he will certainly fail many times when a few simple facts, easily and quickly obtained in the laboratory, would have served to clear up the whole matter. In this progressive age the physician cannot consci- entiously practice medicine without frequent recourse to the all-important laboratory report. The facts so necessary in the routine work are by no means so diffi- cult to obtain, nor is the time and skill required for this work as serious a drawback as it is supposed by some to be. New methods and modifications of old ones have simplified the work so that it is now possible for the busy physician to carry out in his own office the major- ity of the tests necessary in this work. The examination of the urine cannot be given too much prominence in an article of this kind. It is a procedure that should be carried out in the investigation of every case consulting the physician. An erroneous 30 Essays on Laboratory Diagnosis impression seems to be quite common among the laity and even some physicians that the urine is only exam- ined when diabetes or Bright's disease are suspected. No greater mistake could be made. If this were true, how are the insidious beginnings of the above-mentioned conditions to be detected? Unfortunately, many times, the harm is almost irretrievable before the patient is aware of his danger. It is an indisputable fact that in many hundreds of cases the onset of serious organic trouble might have been detected early, provided every case consulting the physician, no matter for what trouble, had been put through an exhaustive and routine exam- ination which included as a component part the complete analysis of a twenty-four-hour specimen of urine. In his excellent work on diagnosis, Leube says : "I would advise particularly never to omit the examination of the urine in headache; we shall thus avoid subsequent self- reproach." From an editorial in the Southern Medical Journal for April, 1909, I quote: "If the general practitioners would avail themselves of these methods of decision coming from chemical laboratories and microscopical findings, few cases of illness would go undiagnosed, and few sufferers lose the benefits of modern medicine." Again: "He is blind indeed who can have the aid of these modern laboratory methods and will not avail him- self of them, strictly as aids and confirmatory evidences of correct bedside judgment." Space will not be taken here to enter into a discussion of the importance of the other laboratory methods of Importance of Laboratory Methods 31 decision. Every case evidencing gastric disturbance should be given a test meal and a careful examination of it should be made. In this way the exact conditions present in many chronic disturbances of the stomach and intestines could be appreciated and steps taken to arrest them. The unpleasantnesses so common when dissatisfied individuals suffering from chronic stomach troubles go from one physician to another, receiving some digestive tablets or other, and maybe a cathartic, and are, of course, only temporarily relieved, could be entirely avoided, at least in the majority of cases, by recourse to the gastric analysis. It is well known that many conditions which are either malignant or on the border line, so modify the condition of the blood that the examination of the blood smear gives information that will make the whole case clear. Again, the fecal examination is a valuable pro- cedure, which, unfortunately, is rarely made because of the unpleasant features and the inconvenience, but which, nevertheless, gives many valuable therapeutic pointers. The value of the report of the bacteriologist on a suspi- cious discharge, a throat membrane, or from a specimen of suspected tuberculous sputum will not be questioned. Therefore, since the methods mentioned above are all essential in the procedures necessary for making a cor- rect diagnosis, it is of the greatest importance that the laboratory should be far more frequently used by the general practitioner. In closing, I feel that I cannot too strongly impress the fact that the laboratory report is of immense im- 32 Essays on Laboratory Diagnosis portance to the physician, for it gives definite informa- tion which usually calls for just as definite treatment. III. SUCCESS IN THE TREATMENT OF CHRONIC DISEASE. Reprinted from AMERICAN MEDICINE, New York, February, igio. CHAPTER III. SUCCESS IN THE TREATMENT OF CHRONIC DISEASE. The average general practitioner is not, as a rule, especially overjoyed when an individual with some dis- ease of long standing comes his way seeking treatment. Most persons suffering from the class of diseases grouped under the broad term "chronic," have gone the rounds of the physicians in the neighborhood, and perhaps elsewhere, and have received little or no lasting benefit. If the physician expects to make a success in the treatment of these difficult conditions, a number of important maxims must be learned, and learned well. It will be my endeavor here to impress a few of these ideas upon the mind of the reader and in this way enable him to carry out with much greater success the treatment of chronic disease. Since a correct diagnosis is usually more than half the battle, it stands to reason that the time and trouble given to the investigation of a given case are time and trouble well spent. If a physician fails in the treatment of any chronic affection, assuming that that particular case is not absolutely "incurable" (and, fortunately, there are very few conditions met by the progressive medical man that are entirely beyond his skill), the fault is to be found either in his investigation or his therapeutic acu- men. Most frequently errors or shortcomings are in the diagnosis rather than the treatment, for the great and 36 Essays on Laboratory Diagnosis ever-increasing progress in medical science, especially along lines of treatment, is all duly chronicled in the various medical journals, and in this way is just as avail- able for the physician at the remote country cross-roads as for the city physician with his medical society meet- ings and clinics — if they both read. On the other hand, while it is granted that there are many books and ar- ticles of special informative value to the man who is anxious to increase his diagnostic skill, there is, of course, no book or article that will tell just what is the matter with Mr. Brown or Mrs. Jones. Successful work naturally entails close personal in- vestigation, and unless more than the ordinary attention is given to this most important part of medical practice the results, or lack of results, must necessarily be un- pleasant and unsatisfactory, both from the standpoint of the patient and of his physician. I might cite dozens of cases which have come to my notice in which failure was due solely to what might properly be called "scamped," superficial, or snapshot diagnoses. A diagnosis cannot be too thorough. Frequently the investigative procedures which the physician carries out may have led him to make an absolutely correct diag- nosis so far as it goes, but it may not be as complete as it might have been, and as a result, unnoticed condi- tions are allowed to flourish, the existence of which cur- tails very markedly the benefits which his well-directed therapeutic procedures might have otherwise accom- plished. A prominent physician recently said, and rightly: Sucess in Chronic Disease 37 "Shortcomings in diagnosis frequently allow human be- ings to suffer for years who might, were diagnosis made clear, be healthy useful citizens all that time." He spoke of a habit to which some of the profession are unfortu- nately addicted, "of skipping over the real diagnosis altogether, and rushing pell-mell into the treatment, so- called." The diagnosis of chronic disease is not reached as rapidly as that of typical smallpox or diphtheria; nor does the patient expect it at once. I well remember a difficult case in which the diagnosis was not arrived at for three months — but it was finally right, and a condi- tion of many years' standing was first modified and then cured. In the majority of cases we must treat not merely a disease alone. It must be evident, for example, that a patient suffering from tuberculosis should not merely receive treatment with reference to the particular infec- tion with the tubercle bacilli alone. The inevitably low- ered vital resistance, and the associated infection with germs other than the tubercle bacillus, should be looked after just as thoroughly and systematically as the tuber- culin-hygienic treatment is carried out. The digestive apparatus should be watched as closely as the tempera- ture, and very great attention paid to the elimination of waste from the body, as evidenced in the urinary findings. Right here, it might be well to suggest that the old fad of "stuffing" a patient is hardly rational in the light of present-day knowledge, and if the physician takes the trouble to properly look after the elimination 38 Essays on Laboratory Diagnosis of his patient and see just what the "dozen eggs a day" are doing to his patient's metabolism, he would easily recognize that this change is worthy of closer considera- tion, because it is based on good common sense. The estimation of the urinary acidity, the estimation of urea and ammonia, as well as the examination for indican and other abnormal substances in the urine, will all surprise the physician treating cases Of the character under discussion, for by these means he will soon dis- cover that the kidneys are being unduly overburdened, that the intestines are filled with a reeking mass of putre- fying albumin, and that the patient is suffering from a toxemia probably equally bad, if not worse, than the toxemia due to the activities of the tubercle bacillus itself. It will be plain that to accomplish these ends the usual abbreviated methods of physical investigation will not suffice. Recourse should invariably be had to certain laboratory procedures varying to some extent with the history, physical findings, etc. In every case a complete urine examination should be made. If there is rea- son to suspect gastro-mtestinal disturbance, do not be satisfied with answers to a few questions, or even with the most thorough physical examination. Procure and examine the stomach contents after a test-meal given in the proper way. Frequently a fecal examination (chem- ical and bacteriological) will throw so much light on a case, that the unpleasantness of the procedure will be altogether overshadowed by the definite knowledge ob- tained, and the results that this may make possible. The Success in Chronic Disease 39 microscopic examination of pus, sputum or other secre- tions, and not uncommonly a blood examination or a few simple tests of the saliva will be of much valuable as- sistance in the work. In this connection it will not be out of place to remind the reader of the help that a Tuberculin reaction (either that of von Pirquet or Moro) may be. This comparatively new procedure is used alto- gether too little, and has not yet received the attention it deserves. , The blood-pressure instrument or sphygmometer is not used as frequently as it might be. It is compara- tively rare to see an instrument outside of the physician's office in the larger cities or in up-to-date institutions. The blood-pressure is a point of tremendous value, and I am not overstating the truth when I say that it should be estimated as a, routine in the investigation of every chronic case. The new Faught instrument is as simple and compact as one could wish, an ornament, and an essential to every progressive physician's office. ' Another factor which plays a very important part in the successful outcome of the treatment of chronic dis- ease is the co-operation of the patient. It must surely be evident that if the physician is attempting to correct certain disturbances and at the same time certain per- nicious habits or customs of the patient are adhered to in spite of advice to the contrary, the physician is very much handicapped in his treatment, and should not be held responsible for any failure that may possibly result. It might be well here also to refer to the need for regularity in the treatment. This is a very important 40 Essays on Laboratory Diagnosis point. For example:- For the relief of any given con- dition, office treatment may only be required every ten days or so; again, treatment may be necessary two or three times a week; and at times daily attention may be advisable in order to obtain the desired results. It must be plain that if one particular treatment brings a patient to a certain stage, and in a sense prepares him for the next, the omission of a treatment, if a matter of common occurrence, will materially decrease the value of the whole series. It is because of this that the opin- ion is quite prevalent that chronic disease, to be suc- cessfully handled, requires the hospital or sanitarium regimen, since the patient is under full control and can receive such treatment as may be deemed advisable without any break or inconvenience. This is true, but I believe, nevertheless, that any thinking individual, by dint of a few gentle reminders, would have sense enough to see to it that the treatment is as regular as possible, and at- the same time that the advice of the physician is explicitly carried out. A point might well be made here regarding the in- structions given to patients. Many times dietetic and hygienic suggestions are made in the office, and because of these the patient starts out very well. He eschews certain articles of diet as suggested and regulates his living very carefully — for a time. In a few days he forgets one item, then another, until finally he is back to the same old slough in which he was wading before he came to the office for attention. To obviate this, I be- lieve it to be by far the best plan to give definite written Success in Chronic Disease 41 instructions to the patient as to what he should eat and what he should not eat; to give him in black and white the most important general instructions regarding his method of living, and make' your ideas so clear that there may be no mistake regarding them. Of course, a. copy of these instructions will be kept on file with the case history, prescription copies, and other records. The instruction slip may well be shown to some member of the patient's family in order that their co-operation may also be obtained in helping the individual under treat- ment to faithfully "toe the mark." The original initial examination of the patient is not enough. Careful watch must be kept of the changes which may be due to the treatment or to other circum- stances. Personally, I consider it of prime advantage to be able to make frequent urinalyses, for in this way the variations in the metabolism are shown up and the changes resulting from the treatment are made clear. It is often an excellent plan to administer certain reme- dies, using the urinary findings as the guide to dosage. The results obtained are sometimes phenomenal, and no physician once accustomed to these methods will re- vert to the older (but admittedly less arduous) way. As far as* repeated examinations are concerned, the same holds true of the gastric contents, feces, etc. Ofttimes the treatment is having a decidedly beneficial effect, although for a time no great modification of the patient's subjective symptoms is apparent. The progressive favor- able change in the laboratory reports, however, is always a source of encouragement, not only to the physician, 42 Essays on Laboratory Diagnosis but also, when properly explained, to the patient. There is another matter which seems quite difficult to instill into the minds of individuals suffering from chronic disease. I refer to the need for a more ex- tended and systematic oversight of themselves after they may have passed from the close attention or immediate care of their medical adviser. The human body is very like a machine, and if an engineer should mend some broken part, see that it worked properly, and then leave the whole machine to the tender mercies of chance with- out any regular supervision, he would very soon be in serious trouble. Instead, he feels the bearings, oils them carefully, tightens a loose nut here and there, and gen- erally scrutinizes the machine with a special care and watchfulness, in this way anticipating trouble before it comes, and preventing what might frequently cause a serious accident. This same thing is just as true of the human machine, and it becomes the duty of the physi- cian to exercise just as much care and intelligent over- sight as does the engineer. I firmly believe that a peri- odical and regular investigation of any individual wha can be interested in this idea will lead to much more sat- isfactory work in the practice of medicine, and, at the same time, prevent, in their onset, a host of entirely needless chronic diseases. Such systematic care of an individual may often prove a means to very valuable ends, and if this article does nothing more than to im- press upon the reader the great necessity for periodic,, clinical as well as physical examinations, it will be welt worth the time and trouble taken to write it. Success in Chronic Disease 43 In conclusion, I might summarize the following es- sential points : 1. Obtain a thorough diagnosis, no matter how much it costs or how long it may take. 2. Find out all that is the matter with the patient. Do not be satisfied with simply finding some evidence of disease and overlook the rest of the hody and other asso- ciated ' difficulties. 3. Be sure you are right, then go ahead, making use of the most rational methods that you know of, and push- ing all your treatment to effect. 4. Always couple whatever therapeutic method you may be using with the most thorough elimination possi- ble under the circumstances. 5. Obtain the confidence and complete co-operation of the family. 6. Make frequent repeated examinations of the urine and, if needs be, of other specimens. This favors thor- ough work, and gives confidence to the patient. 7. Teach your patient something at each office visit; send him away from your office with an Increased knowl- edge of some matter he was not previously aware of, and thus educate him in the prevention of disease. 8. Make the patient realize that he is liable to get into trouble again, to consult you regularly, and thus prevent the recurrence of disease in its incipiency. IV. AN IMPORTANT ELEMENT OF SUCCESS IN THE TREATMENT OF CHRONIC DISEASES. Reprinted from THE MEDICAL STANDARD, Chicago, October, 1909. CHAPTER IV. AN IMPORTANT ELEMENT OF SUCCESS IN THE TREATMENT OF CHRONIC DISEASES. The treatment of the large class of diseases that goes under the name of "chronic" is probably the most diffi- cult part of the work of the general practitioner, and usually offers more opportunities for failure than any of the other branches in medicine. There are several important reasons for this: First, the difficulty in rec- ognizing absolutely the conditions with which one has to contend. Second, the defective education of the pub- lic, which at present has not reached that point which tells them to visit the doctor early, the majority usually waiting until they show evidence of serious trouble ; and, third, the difficulty in keeping patients under close observation and carefully following the prescribed regi- men. For this reason many sanitariums have sprung up in all parts of the country, where individuals live, eat, receive various forms of treatment by trained as- sistants and are under the direct care of physicians all the time. However, not all those suffering from chronic dis- ease can or will, for many reasons which need not be mentioned here, visit such institutions, and consequently must depend upon the general practitioner for help. Un- fortunately, failures are only too frequent, and usually the reason for this is not far to seek. Perhaps a thor- ough examination of the patient is made by the physi- 48 Essays on Laboratory Diagnosis cian, and perhaps not. Thus, I once met a man afflicted with a serious disturbance of the lung, who assured me that he had consulted a number of supposedly prom- inent physicians, but that I was the first one who had him take off his shirt to examine his chest. Then, again, there may be a most careful discussion of the case, coupled, possibly with a physical examination, after which the patient is sent about his business by the lazy doctor with the prescription for one of his stand-by rem- edies in his pocket. It is admitted that all physicians do not reduce their investigation of the cases coming to them to the degree hinted at above, nevertheless, it is a deplorable fact that the majority take far too little time in the investigation of the conditions present in their patients. Their minds seem to center around the subjective symptoms mani- fested by the patient, and on what facts he may have to bring for the physician's consideration. The findings which are only noted after questioning or at the expense of considerable time are in the majority of cases not brought out. Absolutely nothing adds so much to the success and professional reputation of a physician as thoroughgoing, conscientious diagnostic work. Too much time cannot be spent on the investigation of any given case. Ninety- five per cent of all the failures that I have noticed in my practice among those that have been treated by one or more other physicians have been wholly and solely due to scamped diagnoses. And all the hard feelings, depleted pocket-books and hurt reputations might have An Element of Success 49 been avoided had sufficient time and trouble been taken to make a thorough investigation first thing. I will not take space here to discuss the ins and outs of physical diagnosis, but do wish to call particular at- tention to the necessity, importance and great value of the laboratory report as an efficient aid in solving the riddles which so frequently come to the physician for solution. No one scientific procedure will give so many and so varied therapeutic pointers as the careful and thorough examination of the urine. By an "examination" of the urine I do not mean the simple testing for albumin and sugar, tests which are only the confirmation of definite structural changes in the tissues already established, but rather the extended qualitative, quantitative and micro- scopic examination, which permits of the detection of early functional disturbances, particularly of metabolism, which give warning of the insidious onset of disease in sufficient time so that it may be warded off. I believe that I am not overstating the matter when I say that all cases of chronic disease, without exception, are either due to, or at least associated with, definite disturbances in the metabolic functions of the body. Just what these disturbances are, and the extent to which they have gone, remains for the laboratory man to dis- cover. Just how bad the trouble is will be evidenced by the laboratory report, which then becomes an efficient guidepost to definite, result-bringing medication. One of the most common diseases we meet is tuber- culosis. I will venture the statement that if the labora- SO Essays on Laboratory Diagnosis tory is thought of at all, in the diagnosis of pulmonary- tuberculosis, it is for the examination of the sputum. Recent medical literature contains many references to the determination of the presence of the tubercle ba- cilli in -the blood of those infected with this disease, and it has been declared by some that the bacilli in question are found in practically every case, whether in its incip- iency or far advanced. This must surely be a mistake, although it must be granted that in some cases the blood culture made in the proper way gives definite evidence of the presence of the germ. However, there is another important laboratory ex- amination — the urine analysis. This, it is true, gives no special information as to the presence or absence of the specific germ of tuberculosis, but does give information of tremendous value, since it points out the need for the readjustment of the functions of the body. If the tu- bercle bacilli are attempting to gain an entrance into the body, every untoward influence which might either favor the activities of the invader or hinder the activities of the body in general, but more especially the white blood- cells, will be made known. From such an examination we learn whether the ex- creting functions of the kidneys are normal or not; whether the condition of the intestines is favorable to the highest degree of vital resistance; whether the liver is performing its full duty; whether there is an acid in- toxication of the system which would diminish the oxy- gen-carrying power of the blood, thus lowering its germ- icidal properties; and whether the oxidizing power of An Element of Success 51 the cells, or in other words, metabolism, is up to the nor- mal or not. What is the relation of diminished urea excretion to the possibility of infection by the tubercle bacillus? Perhaps not direct or even close, but undoubtedly a dim- inution of this normal waste product may have an influ- ence which will be favorable to the entry of the germ into the body. Now, what effect, if any, do the conditions associated with an excessive degree of urinary acidity have upon this particular matter? I have been told by some that there is absolutely no relation at all between these two factors, and that I had wheels in my head. This may possibly be true, but still the facts evidenced by many laboratory examinations seem to prove the contrary. As a matter of fact, the examination of the urinary excretion of a large num- ber of patients suffering from tuberculosis in all forms showed an invariable increase in the urinary acidity, with the one general exception that in those in which there was retention of the urine with a resulting alkaline fer- mentation and neutralization of the degree of acidity, whether normal or excessive. This is no acpident or mere coincidence; it is a finding which will be noted in practically every case, and fortunately is one which brings with it a knowledge of a very simple, satisfac- tory and successful therapeutic measure. While the disturbed metabolic conditions causing sys- temic acidemia may not be thoroughly changed, yet the increase in the diminished normal alkalinity of the blood 52 Essays on Laboratory Diagnosis can be immediately accomplished, with a resulting change for the better in its oxygen-carrying capacity. It must not be supposed that because I have made this statement, that the use of sodium bicarbonate or alkalies in general is advocated as a specific for tubercu- losis. Far from it. But I thoroughly believe that the use of this drug, or others giving similar results, will do much to favor the natural resisting power against dis- ease in general and tubercle bacilli in particular; and thus aid the individual in the hard battle which he has to fight. What has been said above is not only true of tuber- culosis ; that is not the only "chronic" disease. There are many diseases, some of which, perhaps, are not spo- ken of by any one definite name, yet which most as- suredly can be treated. Take, for instance, the tendency or susceptibility to "colds." Some individuals have a cold almost every month; others take the annual "cold" as a matter of course, and when the time comes for its appearance, quinine, aspirin, acetanilid and other frequently-used remedies are the only things thought of. No attention whatever is given to the cause of the cold, for this is thought to be too simple a matter to require investiga- tion. Supposing an examination of the urine were to be made in the investigation of an individual otherwise seemingly well, but who has just caught a severe cold. In ninety cases out of a hundred there will be found an excessive degree of urinary acidity. Probably indi- An Element of Success 53 can will be present to a greater or less extent, with both the amount of urine and of total solids materially dimin- ished. Are these findings mere coincidences ? By no means. Indeed, are they not rather evidence of definite disturb- ances which may and should be rationally and success- fully treated. If this is so, is the treatment of a cold complete when soda is administered in the proper dose ? Not at all ; but if there is an excessive degree of acidity, alkalies un- doubtedly are called for; if the physician in addition desires to use an antipyretic, or an analgesic, or a soporific, or any other remedy, he may, of course, do so, certainly. The foundation of all chronic disturbances, from rheumatism to neurasthenia, and from tuberculosis to a common cold, is due to a change in the normal metab- olic functions of the body. Just the exact spot where the difficulty is concentrated, or just when or how the trouble began may never be ascertained. Still, it is a fact that the conditions present in the intestines will be found to cause a great deal more trouble than is at pres- ent attributed to them. Indican in itself may be non- toxic, but its presence in the blood, and consequently in the urine, is an evidence of the presence of other tox- ins generated at the same time and in the same locality, and which undoubtedly are the cause of numerous ail- ments. These pathologic substances, usually acid in re- action, neutralize the normal alkalies in the blood-plasma and generally disturb the whole series of the oxidizing 54 Essays on Laboratory Diagnosis functions of the body-cells in general. Just what these substances are is not yet known, but clinical results show that they may be rendered practically innocuous by neutralization with alkalies. To sum up, the investigation of all chronic disease is not complete unless a thorough urinalysis is made, and chief among the points learned from this work is the degree of acidity, since that throws a direct light on>the metabolic and eliminative functions of the body. V. MYSTICISM AND MEDICINE. Editorial in THE MEDICAL STANDARD, Chicago, March, 1910. CHAPTER V. MYSTICISM AND MEDICINE. There was a time, and not so long ago either, when the doctor depended in no small degree upon the mys- tical element for his aid; the more uncanny his proced- ures, the greater his influence over those who came to him for medical service. Only a comparatively few years ago physicians made mystery a prominent factor in their work. Unfortunately, even today there is still a tendency in this direction and there are many physi- cians who consider their knowledge uncommunicable, and under no consideration will enter into explanations of any kind to their patients. In civilized countries we are fortunately gradually getting farther removed from the methods of witch doctors and the influence of fetishes; although, strange to say, some of the ideas still prevalent regarding dis- ease and its treatment are as crude and absurd as the strange orgies of past years about which we sometimes read and throw up our hands in horror. Mysticism has no place in medicine. Nowadays pro- gressive physicians make it a point to take their patients into their confidence, explaining the circumstances and conditions as clearly as possible, and often giving a definite reason for their actions and requests. This in- spires confidence in their work, and the patients, with rare exceptions, follow with evident interest the prog- 58 Essays on Laboratory Diagnosis ress made in their treatment from day to day. It is unfortunate that many physicians still have the erroneous notion that their knowledge is of such a kind that it cannot well be imparted to the layman. This may to a certain extent be true ; we do not pretend that abstruse medical problems, which may be hazy even to the student of years, can be explained to the full satis- faction of those unlearned in medical science but we do contend that a rough, general idea of the processes of the body that may be involved in the particular case in question, and of the raison d'etre of the treatment, are desirable in the proper handling of the majority of cases. Not that the actual remedy or combination of remedies and their dose need be disclosed, or that a morbid inter- est be aroused in the patient — far from it. There is such a thing as going too far and there is no such idea in our minds; but we feel, nevertheless, that there are good grounds to stimulate a greater interest in the edu- cating factor of the general practitioner's work. The educating physician — the man who is not afraid to take a few minutes of his time to give a reason for his action — is a constant source of valuable and helpful knowledge to his patients, and far from confusing their minds, by giving a reasonable account of his work, he makes for unwavering confidence on the part of the pa- tient and an intelligent interest in carrying out to the letter the needful personal hygienic reforms which are essential in preventing the recurrence of the disease — conditions which may have been the means of bringing doctor and patient together. Mysticism and Medicine 59 The disadvantages of eliminating mysticism from medicine are npt confined to the patient alone. The confidence thus inspired brings with it actual therapeutic results that are sometimes phenomenal, and the reflex benefit to the doctor who thus makes it his routine to take his patients into his confidence, is evidenced in the increasing prof essional reputation that invariably follows work of this kind. With intelligent confidence comes intelligent cooperation — an absolute necessity in the hard struggle so often needed in the treatment of chronic con- ditions. We are continually admonished in moral philosophy to "be open" — "be honest" — ''be above-board," and we firm- ly believe that a little more straightforwardness and a little more frankness in medicine would have its advan- tages. The wise physician of to-day is the one who re- gards himself as the educator of such individuals as may come in contact with bim. In explaining various matters that may come up from time to time, he safe- guards their bodily interests just as the lawyer safe- guards the business interests of his client. His great effort is not merely to remove the symptoms but to pro- tect the patient from his own errors and their unavoid- able results — by education. There is still a large number of medical men who seem to cater solely to the subjective ills of their con- sultants. A man comes irjto the office with constipa- tion — he receives a few pills, Hinkle's, we'll say. No ef- fort is made to determine the kind of constipation, nor to find out what far-reaching effects may already be 60 Essays on Laboratory Diagnosis present. The patient is not looking for this kind of service. He came expecting a pill and got it. Another comes complaining of indigestion, flatulence, eructations, etc. — he, too, gets a supply of tablets and, all too fre- quently, no investigation as to the seat and extent of the trouble is even thought of. He was not expecting more and is satisfied with temporary, symptomatic help. Just as the modern progressive merchant refuses to handle shoddy or to supply it even to those who may demand it, since it would be inimical to the trade to Which he was catering, so the progressive physician re- fuses to do slip-shod work masked with a specious air of mysticism, simply because his patients do not know enough to ask for more than the pill or tablet. There are demands which he should not supply — at least until he is in possession of diagnostic facts upon which to base a sensible rational treatment. There is much room for progress in the education of the public along these lines. They should be taught to appreciate the need for the careful and thorough exami- nation. They should learn the "why" and the need of the clinical laboratory. They should be shown the rea- sonableness of the special care exerted in the treatment of the ills from which they may be suffering. As it is now. the majority will not permit real, thoughtful service without a previous explanation of its need and advan- tages. And simply because this requires work, hard work, too many physicians still clothe themselves with the mystical in medicine, and depend upon chance and a few pills, rather than upon real, dependable facts ob- Mysticism and Medicine 6t tained by careful clinical and laboratory investigation. The physician who acts upon sound principle and re fuses to dispense shoddy in his practice, at least when it is desired, is still a rara avis— rnay his tribe increase f VI. THE ADVANTAGES OF THE URINE EXAMINATION. Reprinted from THE MILWAUKEE MEDICAL JOURNAL, Milwaukee, December, ipop. CHAPTER VI. THE ADVANTAGES OF URINE EXAM- INATION. By dint of persistent work on the part of laboratory investigators, the examination of the urine has at last become generally recognized as an essential part of any thorough medical examination by both medical profes- sion and laity. All first-class insurance companies now require some sort of a urine examination as a part of the usual investigation of the prospective policy holder. The advantages of this procedure may indeed be summed up in a single sentence: "No one diagnostic procedure gives us so many and so varied therapeutic pointers as does a thorough urinary analysis." In the title of this paper, the word "possibilities',' might well have been substituted for the word "advan- tages." The possibilities of the urine examination are by no means as circumscribed as is usually supposed. Even in these days of efficiency in medicine, the ordinary "examination" of the average physician does not imply very much more than the simple tests for albumin and Sugar; and opportunities for making a valuable investi- gation of the condition of any individual are surely missed unless, in addition to the old-time simple quali- tative examination, a thoroughgoing physical, quantita- tive as well as qualitative chemical and microscopic ex- amination is made. Contrary to an impression that is still quite prevalent, 66 Essays on Laboratory Diagnosis the urine analysis does not give information as to the condition of the kidneys alone. True, the presence of certain definite urinary findings is usually considered good evidence of the presence of equally definite disease conditions in the kidney structure itself, but this is only a very small part of the information that can be gained. If this were the only purpose served by the urine analysis, its office would be an exceedingly meager one, for, in the first place, its value would be limited to cor- roboration, simply confirming what has already been ob- served from physical examination, and, in the second place, it would only serve to disclose what is known as terminal disease, i. e., practically hopeless changes in the tissues themselves. Thus the outcome of the common search for albumin and casts in the urine is to demon- strate those diseased conditions of the kidneys which are classed (in honor of a famous physician) under the name of Bright's disease. But by the time these condi- tions are thus shown to be present, the kidney tissues are degenerated to such an extent that the urinary find- ings are of little or no therapeutic value. But, fortunately, since the days of Dr. Bright, the work of hundreds of progressive investigators, both at the bedside and in the laboratory, has proved beyond a shadow of a doubt that the earliest beginnings of kidney disturbance are disclosed in a complete urine examina- tion long before the serious and destructive organic processes have begun. In other words, the functional disturbance is manifested before organic change is pres- ent. And while the course of an established nephritis Advantages of Urine Examinations 67 or Bright's disease is not specially benefited by the urine analysis, if the analysis is made early enough, its insidious onset may be noted and appreciated in time to render valuable preventive treatment. Usually, however, such an examination is not made un- less some special reason arises for making a complete and thorough investigation, and it is only in the excep- tional cases that the opportunity is thus gained to save the unsuspecting individual from the trouble to which he is unwittingly, but nevertheless most surely, becoming a victim. To be of the greatest possible value to the individual the urine examination should be sufficiently complete and exhaustive not only to detect the actual evidences of disease, but to lay bare those seemingly harmless con- ditions which, when consummated, may become serious and all too often hopeless. In addition to this, the fre- quency of the tests is a matter of importance, for, as pre- viously stated, serious trouble is very frequently averted because of the accidental findings of some specific point of importance. To change this preventive measure from a mere accident into a premeditated, systematic search, it is suggested that a regular and thorough examination of the urine be made, from time to time, for such indi- viduals as may appreciate the advantages that such a service would be to them. This affords a Very good in- sight into the ups and downs of their metabolism, or the workings of the intricate parts of the body as a whole. The urinary analysis made periodically, and that, too, without the necessity of the presence of evident ill- 68 Essays on Laboratory Diagnosis health as a reminder of the need of it, enables the man who is "burning the candle at both ends" or living the abnormal sedentary life so very common in large cities, to forestall the conditions that his high-tension life is inevitably causing, before extended damage has been done and chronic disease has seized upon him in the prime of his business or professional life. Probably the most common abnormal findings in the urine of the average individual are those which are due to, or associated with, disordered functions of the aliment- ary tract. From the mouth to the rectum, disturbances which are seemingly trivial mirror their presence un- erringly in the secretion of the kidneys. As an illustra- tion of this, extended experiment has shown a definite relation between pyorrhea alveolaris, a serious and un- fortunately common mouth disease, and the presence of certain abnormal substances in the urine. Again, an eminent French authority has expressed himself as be- lieving that more information of value can be obtained regarding stomach disease by the examination of the urine than by one of the stomach contents themselves, although personally I believe that both examinations in conjunction would offer still more satisfactory service. The diseases of the liver and gall bladder often manifest themselves in their early stages by abnormal findings in the urine, in this way calling attention to the disor- dered condition before it has manifested itself in the usual outward ways. The intestinal canal — that "hot-bed of iniquity" in the human body — shows more deviations from the normal Advantages of Urine Examinations 69 than any other part of the food-canal. Certain poisonous substances manufactured from the putrefying intestinal contents are taken up into the blood, causing innumerable aches and pains, malaise and languor, nervousness and irritability, as well as a host of other very common and equally unpleasant conditions. In the wonderful pro- tective economy of the body it becomes the duty of every part to assist in ridding the blood of any excess of poisonous materials that it may be carrying. The kid- neys have to do a large part of this work, and the pres- ence (and for that matter, the extent of the presence) of these substances in the urine is a sure guide to the seat and extent of the trouble,, and incidentally a danger signal of extreme value. By following its guidance, a halt may be called upon the improper and extended use of the kidneys for carrying off waste products which normally should pass out through the bowels. It must be evident that should such conditions be allowed to continue unchecked, the overburdening of the kidneys with more than their proper share of the work must eventually result in a crippling of their functional ca- pacity. As an index of the nutrition and metabolism of the body the urine stands pre-eminent. If an individual is not receiving sufficient nourishment, this fact will quickly be shown in the urine examination. If the oxi- dizing power of the millions of body cells is deficient or increased, that, too, will be manifested very quickly in the relation between the different substances passed out in solution in the urine. By very extended experiments 70 Essays on Laboratory Diagnosis the various urinary salts, organic and inorganic, have been shown to be very serviceable guides to the condition of the different parts of the body. For example, the phosphatic index and its fluctuations has been shown to have a definite bearing upon the nervous system and its, nutrition, and in this way serves to point out the be- ginning of trouble which might, if allowed to proceed the usual course unchecked, soon go from bad to worse. One might go on ad libitum and enumerate the various urinary findings and their several .importance, but this is not the function of this paper. The main idea of the writer is simply to call attention to the fact that a careful, regular and methodical investigation of the various substances normally eliminated in the urine and their relation to one another, together with a series of tests to prove or disprove the presence of any abnormal substances which might be present, will undoubtedly serve to call attention to the earliest beginnings of chronic disease, and in this way prove one of the most important prophylactic measures that it is possible for an individual to take, no matter whether he may be in seeeming good health or a semi-invalid. Such a service, if made systematically, may in time be classed with the many excellent measures adopted and fostered by the state and municipal governments, which in the present century are beginning to usher in the era of preventive medicine. VII. PROPHYLACTIC LABORATORY WORK. Editorial in THE MEDICAL STANDARD, Chicago, June, 1910. CHAPTER VII. PROPHYLACTIC LABORATORY WORK. The laboratory has been utilized to the full for purely diagnostic purposes; almost too much, one is tempted to think, when one considers how diagnosis has come to be based upon isolated objective conditions which too often represent the last structural changes wrought by disease, rather than upon the functional derangements in which the disease usually has its beginnings. The spirit of the times demands prophylaxis in diagnosis as •well as in treatment, and the physician who would keep pace with that spirit must learn to use his laboratory, not simply for the confirmation of already established -morphological changes in the tissues, as in the demon- stration of glycosuria, albuminuria, and the like, but for the detection of early functional disturbances, especially -of metabolism, which herald the onset of disease, so that it may be successfully headed off. Happily, laboratory men and methods are exhibiting a commendable tendency in this direction. The text ' books, it is true, are still wof ully behind the times, but live men in the laboratory field are pointing out, in timely .articles and monographs, how the test tube and the micro- scope may be given a broader and more helpful range than the mere demonstration of structural breakdowns. The value of urinalysis, in particular, has only just be- gun to be appreciated in its quick, sensitive response to 74 Essays on Laboratory Diagnosis the slightest metabolic derangements. Consider, as an example, the significance of the acid- ity of the urine. To this day the standard text books on clinical diagnosis make absolutely no mention of this important diagnostic feature, the extent of their ref- erence to urinary acidity being usually comprehended in the bald statement that "the urine is normally acid." Yet it has been proved beyond reasonable doubt that the varying degrees of acidity are pregnant with hitherto unsuspected significance concerning the conditions of metabolism, and furnish invaluable data for the interpre- tation and management of clinical cases. • We refer to this simply as an illustration of the truth with which we started out, namely, that the uses of the laboratory are but in their infancy — indeed, the real value of this method of diagnosis has not yet been appreciated or utilized. Of all the means at our command for prophylactic purposes, none offers a more promising field than this very one of the laboratory. VIII. ROUTINE URINE EXAMINATIONS. Reprinted from THE NEW YORK MEDICAL JOURNAL, New York, February 27th, 1909. Copyright, 1909. by A. R. Elliott Pub. Co. ' Reprinted by permission. CHAPTER VIII. ROUTINE URINE EXAMINATIONS. That the examination of the urine is a procedure of considerable diagnostic importance cannot be gainsaid. The physician who makes it a regular practice to per- form a complete urinary examination will have a most decided advantage over his professional brother who is readily satisfied with just the few perfunctory tests per- formed with a test tube, some nitric acid, and Fehling's solution. The majority of the medical profession — the average general practicians — are rapidly reaching a point in their experience where the most careful and complete diag- noses are absolutely essential to their professional suc- cess, and for this reason I believe that the routine exam- ination of the urine will soon be carried out by every progressive practician, no matter where he may be lo- cated, whether in the busy city, with its facilities and competition, or at the country crossroads where the facil- ities are meagre and there is little competition, or none at all. In this particular department of medicine — scientific laboratory work — the time element involved undoubtedly has played a very considerable part in preventing the average man from carrying out these investigations in his own laboratory, but with the progress in technique and the simplification of the methods in vogue, this work 78 Essays on Laboratory Diagnosis is rapidly becoming a much less burdensome matter to the busy man, and the time now required for the com plete qualitative and quantitative urinary examination has been reduced to a minimum. Oi course, the examination for sugar and albumin will always hold a high rank, as the presence of either of these substances in the urine points out definite dis- turbances, but considerable variation is manifested by different laboratory investigators as to the relative im- portance of the various quantitative estimations of the normal urinary ingredients ; at least, if their published arguments are to be accepted. Thus, some men think that the estimation of the urea is by far the most impor- tant individual test, while others place much confidence in the estimation of uric acid. Other writers, again, hold still different notions. As for myself, I consider the accurate estimation of the degreee of urinary acidity of paramount importance, for, so far as my experience goes, a large proportion of disease conditions, both organic and functional, are al- ways associated with disturbance of metabolic processes which so modify the chemical qualities of the blood that, because of these changes, the urinary acidity is markedly increased. Unfortunately this test is rarely carried out by the majority of physicians. A perfunctory test with the prac- tically useless litmus paper is about as far as they go, and it must be admitted that the value of this is almost nil. And, yet, the quantitative estimation of the urinary Routine Urine Examinations 79 acidity is a comparatively simple matter and gives infor- mation that is as definite as it is valuable. The variations offer a very good guide as to the metabolic processes in the individual. The examination of a large number of specimens leads me to believe that high urinary acidity is associ- ated in a majority of cases with low urea output and with other metabolic disturbances, possibly of the uric acid type, but not necessarily so. Again, I have found that high urinary acidity and indicanuria quite frequently are associated, and I begin to believe that this high acidity is due to the same condi- tions causing the presence of indican and the conjugate sulphates. At all events, in patients showing excessively acid urine, bacteriological examination of the faeces in a majority of cases demonstrates a severe infection within the intestines, together with putrefaction of their contents and the inevitably resulting autotoxaemia. Considerable work has been done during the last year or two in the investigation of autointoxication as to its cause and cure, and in this connection Professor Eu- gene S. Talbot, of Chicago, deserves special mention. Dr. Talbot has definitely proved the relation between autointoxication with high urinary acidity and certain mouth diseases — such as gingivitis with pyorrhoea alve- olaris, etc., and his method of treating these conditions, by reducing the acidity of the blood, if I may so call it, using the urinary acidity as the index, is to my mind a decided step along the line of progressive, medicine. It will be found that those remedies that reduce urinary 80 Essays on Laboratory Diagnosis acidity to normal distinctly modify many aches, pains, and inconveniences associated with a high degree of acidity of the body fluids, or, more correctly, a diminu- tion of their normal alkalinity. Fortunately the quantitative examination of the urine as to the amount of acid present has been made an ex- tremely simple matter, requiring as it does only an acid- imcter and a medicine dropper. With these at hand and a very little experience, just as accurate work may be done by any careful person as with the burette in the hands of an expert. I have said nothing here of the all important micro- scopical examination, which should, of course, be made in every case. IX. A NEW INSTRUMENT FOR THE ESTIMATION OF THE URINARY ACIDITY. Reprinted from THE NEW YORK MEDICAL JOURNAL, New York, January 2nd, 1909. Copyright, 1909, by A. R. Elliott Pub. Co. Reprinted by permission. CHAPTER IX. A NEW INSTRUMENT FOR THE ESTIMATION OF THE URINARY ACIDITY. In an attempt to simplify the technique of the various laboratory estimations, which should be much more fre- quently made by every general practician, I have for some time been working with a very simple little in- strument which I found useful in the estimation of the urinary acidity. It is not intended to supplant the very necessary grad- uated buret employed by workers in the larger clinical laboratories, but to provide the wherewithal for the busy man to perform this important test in daily routine. The idea was gained from a very handy little tube invented by Gunzberg for the estimation of the acidity of the gas- tric juice. The acidimeter which I have designed consists of a glass tube so graduated that 10 c.c. is the first measuring point. From this upward the tube is graduated in fifths of a degree to 100°, each degree representing the amount of decinormal sodium hydroxide solution re- quired to neutralize 100 c.c. of urine. The method of using the acidimeter is as follows: The tube is filled with the specimen of urine to be tested, until the lower edge of the meniscus is just on the 10 c.c. mark. Two drops of phenolphthalein indicator solution are added, and then with an ordinary medicine dropper decinormal sodium hydroxide solution is slowly added, 84 Essays on Laboratory Diagnosis lOffV 90*-=- 80°-^ 7D*-|- 60*-§- SO'-f- 40°-f- 5{r-=- 20'-|- ee— - inverting the tube after each addition, until the color of the fluid has been changed from yellow to a light rose pink. The acidity in degrees is now read off on the tube at the level of the fluid. The normal urinary acidity of a mixed twenty-four-hour specimen should be between 30 and 40 degrees. If the urine is alkaline in reaction and it is desired to estimate the degree of alkalinity, decinormal hydrochloric or oxalic acid solution must be used in place of the sodium hydroxjde, the pink color present being just discharged by the acid. The advantages of this instrument are: 1. Facility of handling; it can be carried in the pocket or bag and is not easily broken as is the buret. No stand is required. 2. Accuracy of results, the gradua- tions being just the same as in the standard delivery buret. 3. Price; the first cost is consider- ably less than that of a buret, and, as the acidimeter is far less liable to break- age, the eventual cost is very much less. 4. Simplicity; the general practi- tioner, his office attendant or his wife may be quickly taught its rapid and ac- A New Instrument 85 curate use. I believe that this instrument will simplify the pres- ent laboratory facilities of the medical man, thus in- creasing his diagnostic capabilities and his professional success. X. A STUDY OF THE URINARY ACIDITY AND ITS RELATIONS. Reprinted from THE MEDICAL RECORD, New York, June 5th, 1909. Copyright. 1909, by Wm. Wood & Co. Reprinted by permission. CHAPTER X. A STUDY OF THE URINARY ACIDITY AND ITS RELATIONS. The estimation of the urinary acidity has in the past been considered a more or less useless procedure, the simple test with litmus paper sufficing for all pur- poses. The study of this subject does not seem to have received nearly the attention that it deserves, and it is to be hoped that this paper will serve to empha- size the fact that the quantitative examination of the urine for acidity is a most important procedure and a part of the urine examination which should always be carried out. The mixed 24-hour specimen of urine is normally acid in reaction, this condition being principally due to certain acid salts, in particular diacid sodium phos- phate, NaH 2 P0 4 . The acidity is probably due, in a measure, to other acid salts which are also present, although in considerably smaller amounts. The ex- periments of Voit and others have conclusively proven that uric acid has nothing to do with urinary acidity. The index of urinaryv acidity undoubtedly varies in direct ratio with the metabolic changes going on in the body. The manufacture, as waste products, in the body cells of acid substances — of which sulphuric acid is probably the mpst important — must have a de- cided influence upon this factor. In addition to this, certain products of intestinal putrefaction when ab- 90 Essays on Laboratory Diagnosis sorbed into the blood are eliminated in the urine and thus serve, as will be shown later, to increase its de- gree of acidity. Several factors cause the normal urinary acidity to vary considerably, such as an exclusive meat diet; ex- cessive muscular exercise; highly concentrated urine, due, perhaps, to febrile conditions, after free perspira- tion, or diminished water drinking. Then, too, the internal administration of acids, such as benzoic, phos- phoric or boric acid, and the presence of abnormal fatty acids resulting from pathologic conditions also play their part. Undoubtedly the degree of acidity of individual voidings of urine is quite irregular, and in order that the physician in his diagnostic work may gain an ac- curate idea of the elimination and metabolism of his patients, it is distinctly necessary to make an examina- tion of a part of a mixed 24-hour specimen of urine. This point cannot be too strongly emphasized. The urinary examination is usually not made nearly as fre- quently as it should be, and, unfortunately, when the physician realizes the necessity and importance of this procedure, he rarely bothers to have his patient make a complete 24-hour collection and take a specimen from it. One of the most common factors which has to do with the degree of urinary acidity is the concentration of the urine. That is, if the amount of urine is large, it is normally faintly acid, while, on the other hand, if the amount is below the average, the acidity should A Study of the Urinary Acidity 91 be relatively higher. While this is usually the case, it must not always be depended upon, because it is a very frequent occurrence to find the urine of patients pass- ing considerably above the normal amount, even as high as three or four thousand cubic centimeters per diem, to evidence a considerable increase in the degree of acidity. In fact, an examination of a series of speci- mens of urine from diabetics and patients suffering from those forms of Bright's disease which are asso- ciated with the passage of large quantities of urine leads me to believe that this depraved condition of metabolism is constantly associated with such condi- tions as are evidenced by an excess of acidity due to the increased amount of acid substances eliminated by the body-cells. Dr. A. L. Benedict of Buffalo, N. Y., 1 mentions a factor which 1 think should be much more frequently used and given more publicity. I refer to the term "acid unit." An acid unit practically is determined by the relation of the acidity of a whole 24-hour specimen to the amount, thus: 1 c.c. of urine with an acidity of 1° or 1 c.c. of urine exactly neutralized by 1 c.c. of decinormal sodium hydrate solution is equivalent to 100 acid units. Dr. Benedict believes that the average urine is from one-fourth to one-half the equivalent of the decinormal strength, and that the normal acid elimina- tion in 24 hours should be about 40,000 acid units. This, I believe, is a very good average figure. It means that with one liter of urine the average acidity would be 40°, each degree representing the amount 92 Essays on Laboratory Diagnosis of decinormal sodium hydrate solution required to neu- tralize 100 c.c. of urine. On the other hand, 1,300 c.c. of urine with an acidity of 30° gives us practically the same number of acid units. The same is true of 800 c.c. with an acidity of 50°. It can readily be ap- preciated, however, that this last figure cannot be nor- mal, as the total amount of fluid passed is too low, and consequently the acid-index too high. As has been said before, the accurate estimation of the urinary acidity is a matter of vital- importance, and by making much more frequent use of it the physician will | gain many valuable pointers which will enable him to treat his patients more successfully.. It is unfortunate that so little attention is given to the value of this examinaion. There are many state- ments similar to the following, taken from recent books on the subject: "For the practitioner the mere deter- mination of the presence of an excess of acid or alkali by litmus paper is sufficient." 2 "For clinical purposes the litmus test is sufficient. In view of the many vari- able factors that determine the reaction of the urine — it is usually an altogether futile task to determine the urinary acidity by titration." 3 This is a decided fallacy. The examination of a large number of specimens of urine associated in every case with the clinical findings present in the individual passing these specimens shows conclusively that many unpleasant symptoms and even dangerous conditions are associated with, if not actually caused by, high urinary acidity and those disturbed metabolic conditions causing: it. It is well known that A Study of the Urinary Acidity 93 the urine is usually intensely acid in rheumatic condi- tions as well as in acute fevers, due in all probability to the increased manufacture of acids in the body tissues (a hyperoxidation of the body-cells) and, of course, the usual decreased amount of fluid secreted by the kidneys. That increased urinary acidity is distinctly abnormal seems to me to be proven by the findings which are given below. In a series of over 250 analyses the average urinary acidity was 60°, the lowest being 10 6 and the highest 274°. (These specimens were examined in routine laboratory work.) Many of these individuals were passing urine with an acidity from 300 to 500 per cent, of the normal and with an acid-unit-index of from 100,000 to 200,000 per day (the minimum in this series being 8,030 and the maximum 358,050), very much above the normal amount. The other findings show that in 35 per cent, of these cases casts and traces of albumin were found; and in 83 per cent, of these cases indican was present to a greater or less extent, usually in large amounts. . Eighteen of this series evidenced glycosuria with a sugar content varying from 0.3 to 13 per cent. In these cases the average acidity was 77° , with an aver- age acid-unit elimination of 132,130 — an increase of 330 per cent., and in only one of these was there a positive test for acetone or diacetic acid. From these findings it would" seem to me (1) that there is a distinct association between highly acid urine and autointoxication due to putrefaction of the intes- 94 Essays on Laboratory Diagnosis tinal contents shown by the relation between indicanu- ria and high acidity; (2) that in diabetes an excess of acid (not necessarily diacetic or oxybutyric) is the rule, and in addition (3) that this condition of high acidity is very frequently associated with albumin and casts in the urine. It must be evident that an excessively acid urine must be more or less irritating to the kidney cells and tubules secreting it, and it is not unreasonable to sup- pose that such urine is a distinct factor in the produc- tion of casts in the urine, predisposing to serious and definite kidney lesions. From these findings I am con- strained to believe that a definite diagnosis of Bright's disease should never be absolutely made until the urinary findings aside from albumin and casts are nor- mal. (Since compiling these results my attention has been called to an interesting article, ifrom (which I quote: '"The occurrence of albumin in the urine, alone or associated with casts, is not the absolute indication of a nephritis, once believed, as we know that its pres- ence does not necessarily indicate an inflammatory lesion of the kidney. The subject of faulty metabolism as a cause of albuminuria is one which is attracting more and more attention, and deservedly so; for there seems but little doubt that this is the direction in which we must look for the etiological factors of at least one type of nephritis, the interstitial form.") This brings me to an important point. It is quite possible that, to a greater or less extent, the conditions found in the kidney known as chronic Bright's disease, A Study of the Urinary Acidity 95 or interstitial nephritis, are in a measure due to those conditions which produce indican in the urine and high urinary acidity, and consequently the regulation of these conditions, the elimination of indican from the urine and the reduction of the acidity to normal should be distinctly valuable prophylactic measures. Another point of interest is that in the majority of cases, probably from 60 to 75 per cent., where the urinary acidity is excessive and indican is present, the urea elimination is invariably below the normal. From the findings in my 250 examinations the urea elimina- tion was reduced to an average of 60 per cent, of the normal (taking 30 gm. as the normal daily output) in as many as 81 per cent, of the whole series. Dr. Foxhall, in a very interesting paper in the London Lancet, 5 has said that if the average urea excretion is below 1.4 per cent, for 10 or 15 days it nearly always indicates definite renal damage. And so from this it would seem that conditions under discussion — high urinary acidity and indicanuria, and the low urea- index — are very closely related, and have a definite ef- fect, the one upon the other. Right here I wish to emphasize the fact that the quantitative estimation of the normal substances ex- creted by the body through the urinary channel gives definite information as to the actual metabolic activ- ities of the body, which information should be of great value in the examination of the majority of those in- dividuals consulting the physician; while even the most careful examination of a complete 24-hour collection 96 Essays on Laboratory Diagnpsis for abnormal elements only assists in the diagnosis if certain definite disturbances are present, the frequency of which is not to be compared with the abnormal meta- bolic states which are unfortunately so very common. No one finding in the urine examination is of in- fallible diagnostic proof, as has already been stated regarding casts and albumin. Those laboratory facts- which tell us of the exact status of the body functions are especially valuable when one is dealing with chronic conditions which do not prevent the patient from con- tinuing his usual vocation. This general idea of the extent of the. metabolic functions of the body is un- fortunately very seldom known in the routine work of the average man. The test for albumin and perhaps sugar, in addition to the estimation of the specific gravity, is about all the "urine examination" usually clone, and very rarely is a 24-hour collection demanded.. Rather than forestall possible difficulties he advises a. complete urinalysis only in extremis, and even then not too frequently. In this connection it might be well to quote from an excellent article by Dr. Cruise in the Lancet. In this article he says : "Every cautious physician exam- ines the urine for albumin in all serious cases of -ill health, and not infrequently comforts himself and his- patients when he finds that this substance is absent. I doubt that I am in error in adding, on the other hand,, that very few practitioners attempt the quantitative es- timation of urea in such cases. Nevertheless the im- portance of ureametry is far greater than testing for A Study of the Urinary Acidity 97 albumin alone, because while the latter is often present, and signifies little, and may be absent in very grave cases, the quantity of urea is a matter of serious and often vital consequence." And to this must be added that the estimation of the acidity will very quickly give an idea as to the general metabolic conditions of the patient, for, as has already been shown, this is nearly always associated with diminished urea. Regarding the collection of the specimen of urine several matters of importance require consideration. In order to get correct results it is necessary for a whole 24-hour specimen to be collected, care being taken to instruct the patient as to the proper method of doing this. During the collection the vessel should be kept in a cold place, and preferably five or ten drops of chloroform placed in the vessel to preserve the urine from fermentation. The test is then made as soon as possible after the receipt of the specimen at the labora- tory. Of course, some specimens will be alkaline in re- action, and in a majority of cases this will be found to be due either to retention of the urine, cystitis, or fermentation during the collection and transit of the specimen. The microscopic examination usually con- firms this by showing the presence of either pus cells and various forms of epithelial cells, or crystals of ammonio-magnesium phosphate, or both. If the above methods are carried out, practically no error will be caused from the lack of proper preservation of the 98 Essays on Laboratory Diagnosis specimen. So far nothing has been said regarding the method of estimating the urinary acidity. As yet no one method is scientifically accurate, for since the acidity of the urine is not due to any one acid or acid salt, the selec- tion of a suitable indicator is a matter of considerable importance. Different indicators vary greatly in the degree to which they are affected. Methyl orange, congo-red, etc., are more sensitive to the OH-ions of the alkalies, while phenolphthalein, rosolic acid, etc., are more sensitive to the H-ions of the acids. Litmus in its affinities occupies a place somewhere between these two groups. As has been stated before, the urinary acidity is due chiefly to the salt with the formula NaH 2 P0 4 , which reacts acid to phenolphthalein, the neutral point with this indicator not being reached until enough sodium hydrate solution has been added to convert this salt to that with the formula Na 2 HP0 4 . As a matter of fact, disodium-hydrogen phosphate, owing to dis- association into NaH 2 P0 4 and NaOH, reads faintly alkaline to phenolphthalein. It has been found that this can be diminished by the addition of a saturated solution of NaCl which is neutral in reaction and con- sequently cannot itself affect the reaction. That the addition of salt solution is of value can be proved by titrating to the point where the pink color just appears, and then adding the salt solution, when it will disappear. Salts with the formula Na 2 HP0 4 also exist in the urine, and these react alkaline to methyl orange and A Study of the Urinary Acidity 99 congo-red, while those of the formula NaH 2 P0 4 are neutral to the same indicator. Consequently urine con- taining the above salts and which shows an acid re- action to phenolphthalein, when titrated with methyl orange as an indicator, will display an alkaline reaction, which is not destroyed until enough hydrochloric acid solution has been added to convert the salts of the formula Na 2 HP0 4 into those of the formula NaH 2 P0 4 . Any carbonate present must also be decomposed by the hydrochloric acid before the pinkish tinge indicative of the neutral point is reached. Litmus, which in the presence of the above men- tioned salts gives an amphoteric reaction, is absolutely useless in the titration of urine. A urine which shows a marked degree of acidity when titrated with phenolphthalein as indicator is often strongly alkaline to red litmus paper. Dr. Benedict, in his article, has well said: "The simplest way to deal with litmus is to discontinue it altogether, at least for such purposes as the present. All things considered, the best indicator for determining acidity not due to pure acids is phenol- phthalein, which, on the whole, places the neutral point about where it should be according to our general con- ception of acidity and alkalinity." The most satisfactory method of ascertaining the urinary acid-index is by titrating a definite quantity with an alkali solution of known strength, using phenolphthalein' as an indicator. The technique is as follows : With a pipette or other measuring instrument meas- 100 Essays on Laboratory Diagnosis ure out 10 c.c. of urine and add 2 or 3 drops of the indicator. To this add, drop by drop, from a burette, a decinormal sodium hydrate solution until a faint pink color is just obtained. (To those having no burette the use of the acidimeter is recommended.) The amount of solution required to give this reaction is read off and multiplied by ten, to reduce the figures to terms of 100 c.c. This is the acidity in degrees or per cent. This figure multiplied by the number of cubic centi- meters of urine passed in 24 hours gives the number of acid units passed. There are other methods of estimating the acidity — involving other principles. Some add an excess of potassium oxalate crystals to the urine before titration, believing that this makes the results more accurate, by ruling out error from the presence of ammonium salts. Others have various ways of expressing the acidity j some use terms of phosphoric acid, others terms of oxalic acid, and again others terms of hydrochloric acid. These methods all make considerably more figuring, and they also necessitate the use of an empirical alkali solu- tion which is standardized to equal a certain number of milligrams of phosphoric acid, etc. The above method gives us a very good idea of the acid elimination, and enables one to obtain therapeutic information which is of value. It must be remembered that the usual examinations made in quantitative urine analyses for medical pur- poses are all very crude when viewed from the strictly scientific standpoint. The hypobromite method, which A Study of the Urinary Acidity 101 is probably the best method for the clinical estimation of urea, gives 6 to 8 per cent, error. The estimation of the specific gravity is rarely corrected to tempera- ture, and consequently varies quite a little from the actual specific gravity of the specimen; and the urinary acidity is probably from 5 per cent, to 10 per cent, away from the true figure if an ideal method could be devised for its estimation. But when the results are compared with the average of a large number of simi- larly obtained figures from normal individuals or with the estimations previously made on the same patient, it will be seen that approximate figures are distinctly val- uable because they give comparative information that is just what is needed in the practice of medicine. It is quite possible that it is because of the difficulties associated with the accurate estimation of urinary acid- ity that the matter has remained so much in the back- ground. The physician will not, of course, be as interested in the scientific side of this paper as in the help that it may afford him in obtaining results, and so a few words regarding the principles of treatment which seem to be indicated in those conditions presenting high urinary acidity and the associated conditions may not be amiss. It must be understood that the acidity of the urine varies in direct proportion with the alkalinity of the blood, and that in turn depends upon the general health and vital powers of the body. The normal blood-plasma is alkaline in reaction, due to the fact that it carries in solution certain alkaline salts, especially disodium 102 Essays on Laboratory Diagnosis phosphate, Na 2 HP0 4 , and sodium carbonate. Upon this reaction depends, to a greater or less extent, the ability of the blood to absorb carbonic acid gas, and thus to carry on the good work of elimination by means of the lungs. When the normal alkalinity of the blood is dimin- ished and there is an excess of acid substances in the blood, an acid intoxication results which is called by some acidosis and by others acidemia. Both terms are correct, but since the word acidosis is almost invaria- bly associated with serious organic lesions, such as are present with diabetes mellitus, after chloroform anesthe- sia, and in other serious toxic states, I believe that the term acidemia is more appropriate for the condition which is under discussion at present. It is probable that the blood never becomes acid, as in such cases death would undoubtedly result, since the capacity of the blood for carrying excrementitious substances from the cells to the eliminative organs would be absolutely nil, and thus a general paralysis of elimination would occur. One function of the kidneys is to eliminate from the blood all excess of acid substances, and they are so constructed that they are able, not to filter, but to se- crete from an alkaline blood-plasma an acid urine. Now, if the amount of acid substances formed in the body metabolism is excessive, the kidneys frequently can no longer accomplish the work required of them, when the condition termed acidemia results. These harmful substances are carried around in the blood stream, neu- A Study of the Urinary Acidity 103 tralizing to a greater extent the alkalies of the blood, and thus diminishing its power to carry carbonic acid gas, hence making a bad condition worse. It must be evident, therefore, that a diminished de- gree of the alkalinity of the blood-plasma, evidenced by increased urinary acidity, should be a danger signal of extreme value to the practitioner, as it is positive that an excess of acid products of metabolism in the blood is most harmful, and it should therefore be the duty of physicians treating such cases to attend care- fully to the modification of these particular conditions in addition to changing the causes of the abnormal me- tabolic functions. For some time French investigators have been treat- ing such diseases on the assumption that the reaction of the urine is a definite index to the state of the blood, and with excellent results. Their method of esti- mating the acidity is by Boussingault's titration method, using instead of sodium hydroxide a standard solution of calcium sucrate.( ?) Boussingault does not claim that his method estimates the exact quantity of acid present in the urine, but that it represents the physiological acidity — the acidity which is of interest to the medical man. In those conditions which have as one of their man- ifestations high urinary acidity, it has been conclu- sively demonstrated that the judicious use of alkaline remedies is of distinct value. My friend, Dr. Eugene S. Talbot, of Chicago, has done much original work along this line, and has ac- 104 Essays on Laboratory Diagnosis complished excellent results in the treatment of pyor- rhea alveolaris and other serious mouth conditions by simply cleaning the mouth thoroughly and neutralizing the general systemic hyperacidity with the suitable alka- line remedies, such as sodium bicarbonate, magnesia, etc. Twenty to forty grains of sodium bicarbonate dis- solved in water, with or without other synergistic rem- edies, is administered about one hour before meals and at bedtime. This very soon reduces the excessive acid- ity to normal. That this treatment is of value is evidenced by the resulting influence on the unpleasant conditions which are so commonly associated with the high acid-index. The mental dullness, many aches and pains, irritability and general restlessness, dyspepsia and biliousness, to- gether with the lowered vital resistance evidenced by frequent colds, etc., is modified, the patient begins to mend immediately, and the change is both favorable and marked. The alkalies should be given judiciously, and for not longer than a few days, and a careful watch over the urinary acidity made from day to day. This procedure, associated with the removal of the principal causative factors — intestinal putrefaction, constipation, indigestion, excessive feeding, the sedentary life in gen- eral — soon brings the patient to a more normal con- dition. Right here I can do no better than to quote from a very able article by Dr. Eustace Smith in the British Medical Journal as follows : "Alkalies when absorbed into the circulation increase the alkalinity of the blood, A Study of the Urinary Acidity 105 modify secretion, and, If continued too long, may be- come a fruitful source of anemia and languor. Car- ried out through the kidneys, alkalies reduce or annul the acidity of the urine, and are at first beneficial, but in a moderate dose or in too protracted a course may cause cystitis or even vesical hemorrhage. The effect of alkalies is not alone limited to the local action on the stomach, for when used with judgment they seem to have the power of influencing the whole system for good and setting up a very favorable change, which is not always a merely transitory improvement. We often have occasion to notice the prolonged benefit which fol- lows a course of alkaline waters at one of the many spas both at home and abroad. Acting in this manner, the salts of the alkalies are not so much antacid as altera- tive drugs, which, given in moderate doses for a period of weeks and months, are able, without producing any immediate or striking change, to correct a morbid con- dition of an organ or of the whole system, and set up an improvement which, if not permanent, is slow to pass away. In addition to their value in derangements of digestion, alkalies are of special service in the treat- ment of urinary acidity and the discharge of sand and gravel." Careful investigation will prove that in the majority of chronic diseases, and especially in those diseases which are so very common, such as tuberculosis, rheu- matism, neurasthenia, etc., together with the hundred and one other conditions associated with autointoxica- tion, will usually show a decidedly high degree of acid- / 106 Essays on Laboratory Diagnosis ity, and also a marked increase in the number of acid- units eliminated per diem. When the conditions caus- ing this are modified and the findings in the urine changed, the chances of the patient for recovery are greatly increased, because the body and its cells do not have the extra work of getting rid of. these poisons, and hence can better attend to the work of overcoming the ravages of the tubercle bacillus and of building up the body-structure in general. The study of the urinary acidity and its relation to disease is yet in its infancy, and it is to be hoped that in the future more time and effort may be expended on the investigation of this important subject. My sin- cere wish is that this paper may serve to arouse greater interest in this important matter. In closing, I will say that the time spent in making the quantitative acidity test as a routine will be more than repaid to the general practitioner in the indications for treatment he will receive from this information and the more satisfactory results derived from the better adjusted treatment. XI. ACIDEMIA AND AUTOINTOXICATION. Reprinted from AMERICAN MEDICINE, New York, January 1909 CHAPTER XL ACIDEMIA AND AUTOINTOXICATION. These two most insidious and common diseases or conditions are especially serious because their onset is so often unnoticed and their progress unsuspected until material damage has been done. Usually found together, they are unfortunately becoming more common in this country. To speak more accurately, acidemia is one of the many forms of autotoxemia which finds expression in divers ways. All the various manifestations, however, give positive evidence of faulty digestive processes, in- active metabolism and incomplete elimination; and are caused primarily in many instances by hepatic insuf- ficiency. These diseases are found to a greater or less extent in sedentary men and women. In a series of urinary ex- aminations it is surprising to note how many specimens respond in a marked degree to the test for indican, and almost invariably present a high acidity. The first evidence of acidemia is usually a feeling of dullness or laziness, with an occasional headache. The individual complains probably of "not feeling well." He is, of course, not yet sufficiently inconvenienced to con- sult a physician, and the condition is allowed to gradu- ally become worse. The bowels are always quite irreg- ular in action, at times moving too freely and again 110 Essays on Laboratory Diagnosis being moderately constipated. Later the breath becomes foul, the tongue coated, the stools bad smelling, often having an offensive, putrid odor, and in many patients dark rings form under the eyes. The effects on the temper are often marked, and per- sons previously kind, affable and agreeable become mo- rose and show "streaks" of ill-temper and rudeness. The mind is not as clear as before, and the afflicted individual often finds it hard to recall names or data that were for- merly quite familiar. Occasional pains are felt in vari- ous parts of the body, usually varying quite a good deal in severity and persistence. These may be ascribed to "a touch of rheumatism" or "just a little cold," and are naturally treated in a haphazard manner with little or no lasting results. Things go on from bad to worse until some neuralgia, arthralgia or other acutely painful con- dition causes the sufferer to demand the physician's at- tention. Should he be fortunate enough to secure a thorough physical examination, no serious conditions are brought to light, unless some other disease-process is also present. He receives, as a rule, a more or less brisk cathartic and is reassured by the usual "You'll be all right in a day or two." If, however, the urine should be examined, several important departures from the normal will be noted. The amount is usually diminished, the total acidity is found to be very high and the total solids low. The acid- ity shows an increase above the normal of 35 to 40 or even 100 per cent. The test for indican rarely shows its absence. Acidemia and Autointoxication 111 The cathartic routinely given serves, of course, to eliminate a large amount of stagnant, putrefying ma- terial from the bowels, and, temporarily at least, the patient is made "better." However, if the cause of the trouble is allowed to persist, the previous conditions soon return, and the patient grows steadily worse. The stomach gets out of order, the appetite fails and the mouth conditions often become serious. Teeth decay rapidly, not from lack of care, but from the acid saliva that is invariably present. Neurasthenia, mental irrita- bility, the "blues," insomnia, neuritis, neuralgia, dyspepsia and a large number of other diseases are often encoun- tered, and the patient is apt to become sooner or later a nervous wreck. In this condition he goes from one physician's office to another without permanent benefit. At times he feels a little better, and again he is much worse, until at last he falls an easy victim to some seri ous disease, such as pneumonia, typhoid fever or tuber- culosis. From, the foregoing it is evident that it is advisable in all cases to make a urinary analysis. Leube has well said: "I woud advise particularly never to omit the ex- amination of the urine in headache, even if it is of a purely intermittent character. We shall thus avoid sub- sequent self-reproaches." The laboratory report will give definite grounds for initial rational treatment and the subsequent urinary ex- aminations will show the results of the treatment. The saliva, too, should be tested with blue litmus paper — a very easy procedure of considerable value which should 112 Essays on Laboratory Diagnosis be carried out much more frequently in the routine of office or bedside consultations. The administration of salines, suitable hepatic stimulants and antacid remedies for an extended time, to be governed by the results on the urinary and salivary acidity, will in time regulate matters very satisfactorily. Intestinal antiseptics such as B-naphthol, the sulphocarbolates and other similar substances are of great assistance in reducing bowel putrefaction. The proteid rations should be materially reduced, especially the more easily putrefying meats. In closing, it may be well to add a few words. Most authorities deny that acidemia or autointoxication are diseases per se, and this is doubtless true. They are a serious menace to the average individual in that they lower the general vital resistance, making the patient much more susceptible to all diseases, infectious or not. The danger of these conditions is in direct proportion to their insidious onset. They should always be thought of when patients come complaining of obscure ailments. They are easily detected if the physician gives the proper weight to the laboratory findings and makes it a routine practice either to examine the secretions for himself or have it done for him by some competent laboratory expert. Once found and treated before the conditions have resulted in serious organic changes, the treatment is not only easy, but eminently successful, bringing new laurels to the man who thinks. XII. ACIDEMIA: SYSTEMIC HYPO-ALKALINITY. Reprinted from THE MEDICAL BRIEF, St. Louis, August, 19 io. CHAPTER XII. ACIDEMIA— SYSTEMIC HYPO-ALKALINITY. The whole of the vital economy hinges, as all know full well, upon the condition of the blood. "The blood is the life." For many reasons, of which the above is one, few subjects are of more actual clinical interest to the phy- sician than the study of the disease-resisting faculties of the human body. All diseases, and, indeed all our attempts to cure them, are in a large measure depend- ent upon the proper exercise of the metabolic functions of the countless millions of body cells. The matter, then, of the adequate elimination of waste and the proper neutralization within the organism of the poisonous substances manufactured during the processes normally carried out in the ordinary systemic activities, becomes one of paramount interest to us as physicians, for do we not depend upon the vital capacity of each cell, col- lectively called the "vital resistance," for the effective carrying out of our therapeutic measures? One of the most important factors, which, it is be- lieved, should be more generally taken into considera- tion, is the alkalinity of the blood plasma; for there is unquestionably a very close relation between this fac- tor and the all-important interchange of gases carried on. The proper exercise of the oxygen intake and the carbonic-oxide elimination hangs upon the blood alka> 116 Essays on Laboratory Diagnosis linity, for it is essential that free alkali should be pres- ent in the blood in order that the loose chemical hemo- globin combinations can occur, which are so necessary to the efficient performance of the function of gas-inter- change. If this is true (and physiologists. are unanimous as to the absolute necessity of a certain amount of free alkali in the blood), the immense import of the proper degree of blood alkalinity becomes quickly apparent. It is an unfortunate fact that only a very few physicians are studying this matter with the interest which its prime importance would seem to warrant. The study of the actual degree of blood alkalinity is no easy matter, even for the well trained expert with his costly and intricate apparatus; and because of this, the estimation of the amount of titratable alkali in the blood serum is only rarely made. It so happens, how- ever, that one can gain a very good idea of the de- gree of systemic alkalinity by a study of the acidity of the urine. It is not unreasonable to suppose that the acidity of the urine is in close relationship, if not actu- ally in direct ratio, to the blood acidity, or rather alka- linity. This being the case, the tedious, expensive and altogether impossible test of blood alkalinity in the rou- tine of the general practitioner is rendered unnecessary, and in its place the very simple quantitative estimation of urinary acidity may be made. It is not claimed that the relation between the actual amount of free alkali in the blood and the amount of titratable acid in the urine is absolute and positive; but Acidemia — Systemic Hypo- Alkalinity 117 experiment has shown that the fluctuations of the urin- ary acidity in health and disease have a very important influence over the bodily functions. The study of dia- betic acidosis, as well as of the metabolic changes which are so frequently brought about during and after chlo- roform intoxication, has conclusively shown that there is great danger to be anticipated from the presence of certain acid substances in the blood, of which oxy-bu- tyric acid and its congeners -( diacetic acid and acetone) are the most readily appreciated in the laboratory. The acidosis referred to above is quite another mat- ter from the condition of systemic dealkalinization un- der discussion in this paper. For this reason the term "acidemia" is used in order that the distinction and evi- dent difference may be known. Suffice to say that acid- osis is a condition of systemic hyperacidity in which oxy-butyric acid or its congeners are always present; whilst acidemia is a systemic acidity (or hypo-alkalinity) which is far more frequently encountered and which does not show evidence of the presence of acetone in the blood or urine. This latter condition — acidemia — is not considered to be nearly as dangerous as the more generally known acidosis, for the simple reason that its far-reaching influence has not yet been appreciated to the full. It is, however, a dangerous condition, if for no other reason than that its altogether insidious onset and its treacherous influence are all too often not appreciated until some more or less serious condition calls the attention of the patient to a state of affairs that is far from easily righted. In other words, the 118 Essays on Laboratory Diagnosis one-time simple, functional derangement has by then become a definite organic disease. It is claimed by some that the urinary acidity is of little or no importance because it cannot be accurately estimated. This may, indeed, be true; but one may be pardoned for disbelieving such statements when actual results — obtained hundreds of times — prove the con- trary. Realizing this, I unhesitatingly state that acid- emia or systemic hypo-alkalinity is a frequent, insidious condition, evidently due to some metabolic dyscrasia which is quickly and easily gauged by the estimation of the acidity of the urine; and which, because of its widespread occurrence, associated with almost every form of disease known, ought to be thoroughly under- stood by every physician, and its influence noted in con- nection with the study of every disease, from the com- mon cold to incipient tuberculosis. Experience has taught that this condition of acid- emia is, in the majority of cases, either actually due to or, at least, very closely associated with, intestinal auto- intoxication. One very frequently finds indican to ex- cess in urine showing a high acid-index. This is further exemplified in the fact that the successful, or, for that matter, the unsuccessful attempt at the removal of indi- can by the usual orthodox measures will cause a ma terial reduction in the urinary acidity, even though the diet remain the same and not one grain of alkali be given. Evidently, therefore, intestinal putrefaction is the one prolific cause of acidemia. This idea is not un reasonable when one remembers that indican (potas Acidemia — Systemic Hypo-Alkalinity 119 sium indoxyl-sulphonate) is really an acid salt, and in- dol-acetic acid and the other associated toxins are acid in reaction. Another fact which goes to strengthen this conten- tion is that in cases evidencing urinary hyperacidity and indican, the urea index is usually very low and the amount of ammonia correspondingly high. This change in the relation of the substances eliminated in the urine is doubtless due to the fact that the excess of acid sub- stances in the blood has united with and neutralized the alkaline urea precursors and formed ammonia prod- ucts. It will be remembered that the amount of ammo- nia excreted in diabetes is usually enormous — for the selfsame reason. The body, in its attempt to neutralize the excess of acids formed through the faulty diabetic metabolism, eliminates as much of the acid as possible in combination with the much-needed systemic alkalies, the ammonia content being consequently very high; at times several grams per diem (0.7 gram in 24 hours is the normal). The resulting alkali-hunger makes bad very much worse, and can only be satisfied by the ad- ministration of alkalies. It is well known that the best treatment for diabetic coma is the intravenous injection of an alkaline solution, preferably of sodium bicar- bonate. The influence that acidemia has over the system is naturally very widespread. With the crippled gas-inter- change, the whole of the eliminative activities are disor- ganized. Toxic anemia is very common. Digestive dis- turbances, originally the underlying factor in the pro- 120 Essays on Laboratory Diagnosis duction of this condition, are now rendered more com- plicated and unmanageable. The nervous equilibrium is disturbed, and we are just beginning to enter a realm of research which it is confidently believed will show a close connection between acidemia and many func- tional neuroses. Several severe eye disturbances, in- cluding retinal hemorrhage, recurrent corneal ulcer, etc., have been seen with which the urinary hyperacidity had some close connection. Skin diseases are frequently found in the acidemic. The relation between alveolitis (pyorrhea alveolaris) and systemic hypo-alkalinity is demonstrated beyond a doubt. Many experiments have shown that the emunc- tories, among which the kidneys rank first, are badly crippled by the hypertoxicity of the urine, and it is pleasing to read that our contentions regarding the re- lationship between acidemia and incipient Bright's dis- ease have been positively proven. Roubitschek, in Berliner klinische Wochenschrift, May 2, 1910, relates the results of a series of experiments on rabbits in which he produced constipation by feeding oats and administering opium and tannic acid. In a week albu- men and casts were found in the urine. The albumen increased steadily to 0.50 pro mille. Autopsy after two or three weeks showed the liver and spleen hyperemic and the kidneys enlarged, dark red, normal consistence, and with capsule closely adherent. Punctiform hemor- rhages were present in the capsule and hemorrhages were also found in the glomeruli. Lastly, but most important of all, this condition Acidemia — Systemic Hypo-Alkalinity 121 lowers the vital resistance and lays the unsuspecting individual open to infections and diseases of all kinds. If all the foregoing is true, the presence of an ex- cess of acid substances in the blood or a diminution of its free alkali, whichever term one chooses, should not only be looked for, but its untoward effects modified as quickly as possible. This is usually not a difficult matter to accomplish. Alkalies are cheap, easy of ad- ministration, and, when properly given, are practically harmless. Hence the therapeutics of the alkalies may well be given increasing attention, since their judicious use will produce a marked beneficial effect in these cases of acidemia. The treatment of acidemia does not, of course, con- sist in the mere administration of alkalies until the urine is of normal acidity. This would be purely empiric medicine. On the contrary, if worth-while results are desired in the treatment of this condition, the whole sys- tem must be thoroughly unloaded and a regular house- cleaning instituted. Besides the free use of salines, alone or following a dose of calomel or phenolphthalein, it is often well to look carefully for fecal impaction, especially at the flexures of the colon. If this is pres- ent, one or more high injections of oil may be given. Ordinary "sweet oil" serves the purpose well, but the addition of 1 per cent of icthyol considerably increases the efficiency of this treatment. Four to six ounces arc injected as high as possible into the colon; the patient is instructed to lie with hips raised and the clothes or bed carefully protected. If the oil can be retained all 122 Essays on Laboratory Diagnosis night, so much the better. Tonic measures may or may not be given, depend- ing entirely upon the circumstances present in each case. Physical measures are of immense value. The sinusoidal current to the abdomen, interrupted galvan- ism, and even faradism, are of service. Abdominal manip- ulation and exercise with or without resistance are use- ful. Prolapse of the viscera should always be corrected ; and this will be found to be very frequently necessary. Tonic hydrotherapy (hot and cold applications, douches, etc.) to abdomen, liver and spine are helpful. In fact, anything that will serve to enable the abdominal walls and bowel musculature to regain their normal tonicity and vigor will be of service. The alkalies may well be combined with other syn- ergistic remedies. Several formulas have been in use for some time. One of them, suggested by Doctor E. S. Talbot, now goes under the name Sodoxylin (Ab- bott) and has the following formula: Sodium Bicarbonate ... gr. xx Sodium Sulphocarbolate . . . gr. ijss Sodium Sulphate .... gr. v Colchicine .... gr. 1-500 Xanthoxylin ..... gr. 1-6 Sugar, Aromatics, Etc. . q. s. ad gr. lx Sig. : One teaspoonful two or three times a day be- tween meals and with plenty of water. Another formula might be mentioned: Sodium Bicarbonate gr. xxv Sodium Sulphocarbolate . gr. x Phenolphthalein . . . . gr. ss Sugar q. s. ad . . . gr. lx Acidemia — Systemic Hypo-Alkalinty 123 Sig. : Make in powder or granular form. Take a teaspoonful, followed by a large draught of water (hot or cold) between meals. Still another therapeutic measure which must not be forgotten is the use of living cultures of certain lactic acid bacilli. Massol's bacillus, or the Bacillus bulgari- cus, seems to have a decidedly beneficial action in these cases, and its use cannot be too highly recommended if the cultures are virile and enough of them are given. In closing, it might be well to mention a combina- tion of conditions that may put the physician off his guard and bewilder him in his study of these cases of acidemia. In a number of instances it will be found that the patient is evidently suffering from toxemia with all the usual symptoms, including headache, ma- laise, bad breath, anemia, indicanuria and the hundred and one associated disturbances; but the urine is almost alkaline. One must here exclude the possibility of alka- line fermentation of the urine either in vivo or in vitro. Eliminate the. possibility of cystitis or retention. Keep a little chloroform or other preservative in the specimen from the commencement of its collection in a covered vessel. Then carefully watch the patient and the vari- ations of the acidity from day to day. It will be fre- quently found that there comes a crisis or period in which the physical symptoms are materially worse. The patient is prostrated with fever, chills and general dis- disability, and the acidity is tremendous. In these cases, instead of eliminating as much of the effete matter as possible, the patient is storing up the 124 Essays on Laboratory Diagnosis poisonous products in his system until the body makes a special effort to right matters and the so-called "crisis" comes. In such cases the treatment should evidently be exactly the same. The clean-out treatment, the tonic measures and the alkaline draughts will serve to reduce the rate of manufacture of the toxins and neutralize them in the tissues before they get into the blood and thence through the kidneys to increase the acidity of the urine passed. Such cases have proved a stumbling-block to many beginners in the study of acidemia and its clinical value; but the investigation of a few cases for a week or two will convince one that this condition of retained waste is even worse than when the acidemia is plainly noted by a study of the urinary findings. Acidemia is far too important to be longer over- looked. Probably your next patient has it. Try the test and see. XIII. THE RELATIONS AND CLINICAL SIGNIFI- CANCE OF THE URINARY ACIDITY. (A paper read before the Illinois State Medical Society, Danville, May, 1910.) Reprinted from THE ILLINOIS MEDICAL JOURNAL, Springfield, October, 1910. CHAPTER XIII. THE RELATIONS AND CLINICAL SIGNIFI- CANCE OF THE URINARY ACIDITY. One is tempted to believe, from a study of the liter- ature on this particular subject, that it is of little or no significance. In fact, very little space is devoted in most text-books to the discussion of the importance of the urinary acidity. One learns that the reaction of the urine is normally acid, that at certain times of the day it may be amphoteric or even alkaline, and that an alkaline urine is in all probability an evidence of cystitis or retention. The litmus paper test is referred to, the burette method of estimating this factor is mentioned, and, generally speaking, the whole subject is passed by very superficially. In addition to this, current medical literature has until the last year evidenced a decided paucity of discussion along this line. It is encour- aging to notice that as medicine progresses a greater interest is being manifested in the so-called "minor mat- ters" and the study of the urinary acidity and its rela- tions will soon be considered in its proper light. The information obtained by the careful estimation of the urinary acidity is of very great clinical import. In my estimation it is one of the most important of the urinary findings and a factor which should be known as . a matter of course in the routine examination of every case; for the conditions associated with a de- creased blood alkalinity have been found time and 128 Essays on Laboratory Diagnosis again associated with several other definite findings, and it has been shown by laboratory experiment, as well as by clinical experience, that therapeutics based on this particular finding have given most salutary results. The reason that the condition of high urinary acid- ity and the usual associated clinical and laboratory find- ings have not been more frequently found and described together is that they have been seldom looked for. The determination of the reaction of the urine by the obso- lete litmus method is as far as most physicians care to go in their urinalyses. The degree of acidity is esti- mated in the larger clinical laboratories, but it is the exception rather than the rule to find the averge phy- sician taking the time or trouble to make this simple test. "What good is it, anyway?" they say. "If I can see a specimen of urine and make a test for albumin and sugar, and find out the specific gravity, I'm satis- fied." This is an unfortunate state of affairs, for the acid- index is a factor of considerably more than ordinary importance, has a direct and close relation to metabolism and elimination, and is, therefore, a guide of no mean value to the physician who is endeavoring to care for indefinite and obscure ailments. The estimation of the urinary acidity is not a diffi- cult procedure. It can be very simply and quickly esti- mated in the laboratory with a burette, or anywhere with an acidimeter and no other reagents than deci- normal soda solution and a phenolphthalein indicator solution. Some writers have said that this test is far The Relations of the Urinary Acidty 129 from accurate and for this reason have depreciated it. There is not a doubt of the futility of endeavoring to accurately estimate the total acidity by the above method; but in clinical laboratory work we do not ex- pect a grade of volumetric or gravimetric work which can be compared, say, to the work of the assayer or metallurgist. In medicine we are satisfied with approx- mate figures. To prove this, I merely mention the notoriously inaccurate methods in general use for the estimation of albumin, urea and, for that matter, prac- tically every quantitative urinary test save alone the estimation of nitrogen. The fact that the actual total acidity of the urine is a factor which is practically impossible to obtain with any absolute degree of accuracy does not deter the practical physician from making the test. Let us give here an illustration. A specimen is examined and the acidity is determined to be 40 degrees. The amount passed is one liter. The reaction to litmus is, of course, acid. A second specimen is examined and the acidity found to be 120 degrees with an amount approximating 1,500 c.c. The litmus test is also acid. Is there any material dif- ference between the condition of the alkalinity of the blood in these two cases? Assuredly. In the first case the number of acid units is 40,000 (practically the aver- age normal figure) and in the second, 180,000, or a good deal more than four times the normal. Surely there is an evident difference here. Personally, I have encountered no little skepticism regarding the real clinical importance of the matter un- 130 Essays on Laboratory Diagnosis der discussion here. I presume that this is only nat- ural. Too often we are prone to overlook the more common things simply because we do not realize their significance. The "theory of autointoxication," first taught by Bouchard, has within twenty years become one of the most important and widely recognized fac- tors in the pathogeny of all disease, and yet the eminent internist and investigator, von Noorden, himself, admits that: "At first we German physicians were by no means inclined to accept the theory of autointoxication that was being so enthusiastically proclaimed. Of late years, however, our attitude has become more friendly to the doctrine. This change of front is due to the fact that a number of the toxic products of metabolism have actually been isolated and their mode of origin in the organism, and their pathologic effect determined to the satisfaction of the former critics." If I am not greatly in error, the clinical significance of the urinary acidity will be in the years to come one of the essential diagnostic factors. It will be estimated in every case and, to a certain extent, upon its varia- tions will depend the rational treatment of the majority of diseases. In a paper which I wrote in the spring of 1909, and published in the Medical Record early in June of that year, I gave the results of a series of about 250 urin- alyses which proved, to me at least, that there was a close relationship between excessive urinary acidity and indicanuria. My work since then, as well as that of a number of friends and correspondents, has only served The Relations of the Urinary Acidity 131 to corroborate this finding. Evidently the condition which is known to cause the presence of indican in the urine is also responsible for a marked increase in the acidity. In the above paper I also called attention to the fact that practically 25 per cent of the whole se- ries showing excessive acidity also evidenced casts, usu- ally of the hyaline type, and, at times, traces of albumin. It is pleasing to note that investigators elsewhere are corroborating these findings. Von Hoesslin states that albuminuria and cylindruria are in some cases directly dependent upon the acidity of the urine. In these cases albumin and the formed elements disappear entirely or diminish in degree if the urinary acidity is decreased by the administration of sodium bicarbonate. He be- lieves that it is necessary to determine the relationship of all albuminurias to the existing acid-index. Another very common disturbance in the relations of the urinary findings is that with an excessive acidity there is frequently found a markedly lowered urea- index. The total solids are decreased in some cases as low as one-third of the normal. This shows conclu- sively that urinary hyperacidity is associated directly with the metabolism. The urea-content is diminished because the urea-precursors are neutralized by the ex- cess of abnormal acid substances in the blood and elim- inated as ammonia compounds. As a result, the amount of ammonia in the urine is usually excessive in these cases. Then, again, since the solids are often so de- cidedly diminished, it would seem that the organism is storing up trouble for itself in the form of the effete 132 Essays on Laboratory Diagnosis metabolic products which should normally be elimina- ted. This seems to be proved true by the not infrequent "crises" in which the individual who for weeks and months has been eliminating much less than the normal is suddenly taken seriously ill and the urine shows not only a tremendous acidity (265 degrees was, I believe, the highest figure seen in my laboratory), but the solids are also markedly increased. Naturally, in these cases there are abundant evidences of renal irritation. It may not be out of place here to call attention to the fact that upon the normal alkalinity of the blood de- pend two of its most important functions — oxygen-car- bon-dioxid exchange and phagocytosis. Any condition or combination of conditions which would tend to decrease either of these powers must evidently have an import- ant and widespread influence upon the general disease- resisting capacity of the organism. Acidemia, or di- minished blood -alkalinity, will be found in practically all chronic diseases and, for that matter, in many acute diseases; and it is confidently believed that this factor of urinary hyperacidity is of sufficient importance to be known and its variations carefully watched in all cases. One can quickly corroborate these statements by making an examination of the urinary acidity of a twen- ty-four-hour specimen, of course, in the most frequently encountered condition of lowered resistance, the com- mon cold. The acidity is almost invariably increased; and, what is of more importance, demonstrating even more conclusively that this matter is worthy of consid- eration, the administration of alkalies will do much to The Relations of the Urinary Acidity 133 favor the breaking up of the cold. I could enumerate case after case in which the urin- ary findings and ultimate outcome proved unquestion- ably- that acidemia is a condition worthy of ca'reful consideration. Two or three will suffice here: A col- league, while visiting in Seattle, was invited to see a case of severe throat ulceration which was interesting because of the extent of the disease and its intractability. The little girl had been for several weeks suffering with a membranous condition of the throat and pharyngeal walls which was becoming progressively worse. Heroic doses of diphtheria antitoxin, swabbings with silver ni- trate solution and the best treatment that one of the leading specialists could afford seemed without avail. My friend asked if the urine had been examined. No. Might it not be done at once ? Certainly., A specimen obtained in the office and tested in the acidimeter showed an acidity of nearly 180 degrees. A twenty- four-hour specimen which was begun immediately was tested the next day and the acidity found to be practi- cally the same. The case was treated with a sodium bi- carbonate mixture until the acidity of the urine was normal, and within a few days the membrane and every evidence of the condition had disappeared save a marked hyperemia of the pharynx. Again, a prominent business man in Washington, D. C, was suffering from a nervous condition which had baffled a number of the best physicians there. He acci- dentally came under the notice of a friend of mine and it was suggested that the urine be carefully exam- 134 Essays on Laboratory Diagnosis ined. It was found to be excessively acid, and the com- monly-occurring associated findings mentioned before were also thoroughly in evidence. To make a long story short, the sufferer, who had almost given up hope, was treated as an acidemic, and within a few weeks was another man. This sounds almost like a patent medicine story; but it is not. Still another case which I have watched personally for considerably over a year. A young man was suffer- ing from epileptic seizures. When I was consulted, the urine was, of course, examined. It was found to be excessively acid, much indican was present, and the solids were very low. The acidity was reduced, the indican eliminated, and, to make another long story short, the seizures ceased, to return only when the con- ditions were not as carefully watched as they should have been. The only treatment has been to keep down the acidity and to prevent ithe circumstances which caused it. In about eighteen months there have been only two or three attacks and the urine passed before and after them was excessively acid and toxic. In discussing this subject last summer with Dr. Frederic E. Sondern, of New York, he made a remark which will bear repetition here. In answer to a ques- tion concerning the difference between "acidemia" and "acidosis," he said that B-oxybutyric acid or its con- geners was an essential to true acidosis. This, then, shows that there is a decided difference between the acid-condition of diabetes mellitus and the condition called acidemia now under discussion. The treatment The Relations of the Urinary Acidity 135 may be essentially the same, and, for that matter, a part of the underlying cause the same, but the two condi- tions are essentially different and must not be con- fused. Doctor Sondern also said that it would be some- thing worth while if the "acid-substances" which evi- dently cause this troublesome condition could be iso- lated and named. Possibly this may be accomplished later, but in the meantime we must be satisfied with knowing that they are there and that their presence warrants attention. In all probability these "acid-sub- stances" are closely related to the sulphuric acid prod- ucts of intestinal putrefaction, to indolacetic acid, in- dican and skatol. For clinical purposes, however, it is not always absolutely necessary to know the definite scientific name of the causus mali. The fact that it is there and the means known whereby its effects can be counteracted is more than enough for all practical pur- poses. It might be well here to give the principal factors which cause variations in the reaction of the urine. The acidity is increased by autotoxemia, fever, dimin- ished output of urine, the ingestion of an excess of proteid food and certain more or less obscure metabolic disturbances, among which diabetes melutus stands first. On the other hand, the main factors causing a dimin- ished acidity of the urine are alkalies taken internally, the ingestion of fruit acids, cachexia or a marked dim- inution in the metabolic activities of the body, and diuresis. It is well to remember that diuresis decreases 136 Essays on Laboratory Diagnosis the acidity of the urine and that the decrease is pro- portional in degree to the extent of the diuresis, no matter how the increased flow of urine is brought about. One other important factor must not be overlooked. Any circumstance which causes fermentation of the urine, no matter whether in vivo or in vitro, will reduce its acidity. For this reason, when cystitis or prostatitis is present, due allowance for these conditions must be made. Again, the urine should be examined as soon after the collection as possible, and steps taken to pre- vent the onset of the usual ammoniacal fermentation for obvious reasons. It would seem, from the foregoing, that the follow- ing conclusions might properly be drawn: 1. The study of the urinary acidity and its rela- tions is worthy of much wider attention. 2. Its clinical significance is of importance in all disease conditions, but more especially in the indefinite and obscure chronic diseases. 3. The acid-index is a factor of considerably more importance than has yet been supposed, and has an inti- mate relation with the phenomena .commonly found with intestinal putrefaction and autotoxemia. 4. The urinary acidity is not only of importance in diagnosis, but also serves as a valuable guide during the period of treatment. 5. The frequent finding of evidences of kidney irritation would lead us to believe that the conditions causing urinary hyperacidity are important predisposing factors in the causation of nephritis. The Relations of the Urinary Acidity 137 6. The test for the degree of acidity is simplicity itself and can be easily accomplished either with a bu- rette or an acidimeter. 7. The clinical indications and therapeutic possibili- ties suggested by these findings will more than repay one for the slight trouble required in making the tests. XIV. THE URINARY AMMONIA IN ROUTINE WORK. Reprinted from THE MEDICAL COUNCIL, Philadelphia, January, 1911. CHAPTER XIV. THE URINARY AMMONIA IN ROUTINE WORK. I believe I am not overstating when I say that not one pro mille of the men now doing clinical laboratory work in general practice — certainly not one per cent — are mak- ing the quantitative test for ammonia in the urine as a routine. The reader will quickly be able to decide in his own particular case whether I am right or not. There are two great reasons for this state of affairs: It is not known how easy the test is, and how little time and skill it takes ; and its advantages in general practice are not appreciated nearly as much as their importance really warrants. It will be my endeavor in this paper to call attention to the simplicity and accuracy of the so-called Malfatti- Rongese test, to compare it with the expensive and tedious Folin test now commonly used in the larger lab- oratories and to give good and sufficient reasons why the general practitioner should take any of his valuable time in carrying out the test and making the calculations. To begin with the latter consideration: The urinary ammonia index is an excellent guide to the resisting powers of the organism against certain toxemias, af- fording us very definite evidence of an autointoxication by certain organic acids. The repetition^ of a few facts which the physiological chemists have found out for us will quickly explain why this factor is the important 142 Essays on Laboratory Diagnosis clinical and prognostic guide it is claimed to be here. Ammonia is one of the most important products of proteid metabolism. Urea, the most important of the urinary solids, consists of a combination of nitrogenous metabolites, among which ammonia is prominent; urea being, chemically, ammonium carbamide (CH 4 N 2 0). It has been definitely learned that the substances which go to form urea are combined in the liver. Extensive animal experimentation has shown that the arterial blood of animals contains approximately 0.4 milligrams of am- monia, as compared with a corresponding 1.85 milli- grams in the portal blood. These substances before they reach the liver are termed "urea precursors," and, it must be understood, are alkaline in reaction. When the blood is charged to an abnormal degree with the acid wastes formed during the putrefaction of nitro- genous materials in the intestines, and also in a dis- ordered metabolism, in the wise economy of Nature they are promptly combined with the alkaline urea-precursors, thus rendered neutral and practically harmless, and ex- creted in the form of other ammonia compounds in place of urea. Hence one can readily see The variety of casts found is of much diagnostic im- portance. Thus hyaline casts are very frequently found in hyperacid urines as well as in chronic interstitial nephritis; granular and blood casts are more often as- sociated with acute renal congestion or inflammation, while waxy and fatty casts occur in the amyloid, cirrhotic or contracted kidney and in the more chronic forms of nephritis. The presence of red blood-cells, spermatozoa, para- sites, etc., in the urine do not require to be referred to here, as these give evidence of findings which cannot easily be misconstrued. Of the unorganized elements usually found in the urine, the most important are crystals of the amorphous phosphates, calcium oxalate, urates, uric acid, triple phosphates and calcium carbonate. What the Urine Report Means 183 Urates and Uric Acid. — The presence of an excess of urates and uric-acid crystals in the sediment of the urine is almost invariably associated with highly acid urine, although it has been conclusively shown that uric acid does not have any influence on the degree of acid- ity. The continued finding of these crystals points out a disturbed metabolism which has been called by some the "uric-acid diathesis" and which very often is asso- ciated with rheumatism or other so-called "rheumatic" affections. When these crystals are found in the urine, steps should be taken to prevent their persistence, as calculi very often are formed 'from them, causing much trouble. Oxalates. — Crystals of calcium oxalate are not in- frequently found in the urine, but do not yield any very definite clinical information. I have frequently found them in the urine passed soon after a person has eaten freely of rhubarb. Boston believes them to be common in the urine of persons that are overfed and of seden- tary habits and where there is much mental strain. Some investigators believe a persistent oxaluria may be a precursor of sugar in the urine. Triple Phosphates. — Crystals of ammonio-magne- sium phosphate, the most common form of which are the "coffin-lid crystals," are frequently seen. Their pres- ence is evidence of ammoniacal fermentation of the urine, either in the bladder previous to micturation or after passage, if the urine is allowed to stand a long time unpreserved. 184 Essays on Laboratory Diagnosis There are other and less important crystalline find- ings in the urine, but they will not be referred to here because of lack of space and their comparative un- importance. XVIII. THE THERAPEUTIC INDICATIONS OF THE URINALYSIS. Reprinted from THE AMERICAN JOURNAL OF CLINICAL MEDICINE, Chicago. October, 1909. CHAPTER XVIII. THE THERAPEUTIC INDICATIONS OF THE URINALYSIS. Possibly no one other procedure among the routine diagnostic measures carried out by the general prac- titioner gives quite so many and so varied indications for treatment as the urinary analysis. The urinalysis, properly made and rightly interpreted, can be of the greatest practical everyday usefulness to the practicing physician. No attempt will be made in this paper to touch other than the more important points in the routine examina- tion; nor will space be taken to outline treatment for diabetes mellitus, Bright's disease or cystitis. Aside from these important conditions, in which, of course, the urine examination is thoroughly recognized as es- sential, there are many points of vital importance re- garding metabolism which are, unfortunately, usually overlooked. The complete urine examination should be made in the investigation of every case, and always from a part of a carefully collected 24-hour specimen. The exam- ination should include the quantitative estimation of the normal substances eliminated in the urine, and their re- lation one to the other, as well as the usual quantitative physical tests. The first and probably the most important quanti- tative test is for urea. Since urea is the principal nitro- 188 Essays on Laboratory Diagnosis genous waste-product eliminated in the urine its fluctua- tions must necessarily be of importance. The normal urea elimination for a healthy individual should be about 25 grams in twenty-four hours, or practically 2 per cent. Very frequently the urinalysis shows the urea-content from 25 to 50 per cent, and at times even 75 per cent be- low the average, and this is, to say the least, an import- ant point to the physician. It must be evidept that if the urea is not being eliminated, some of its component elements are being stored up in the. economy, to cause trouble later on; or, and this is more likely, abnormal acids in the blood unite with the urea-precursors, prob- ably in the liver, to form ammonia compounds. It has been stated that if the urea percentage is as low as 1.4 per cent for several days in succession there is gool reason to suspect definite renal damage. The successful treatment of individuals suffering from a diminished elimination of urea is no easy matter. The amount of water taken in must be increased materi- ally. An excessive amount of nitrogenous or proteid food should be eschewed, at least temporarily; and if an acidemic condition is present it must be controlled by the use of suitable remedies. Sometimes in cases showing a persistent low urea- index there is an associated disturbance of the thyroid function which could be carefully looked into with profit. The administration of suitable doses of thyroid extract has, in a number of cases, shown a marked change for the better. Frequently the liver is the principal seat of the The Indications of the Urinalysis 189 trouble, the disturbance being due to the proverbial "sluggish liver." This, however, is not necessarily an indication for the ordinary so-called "hepatic stimulants." Boldine (an alkaloid obtained from peumus boldo), has a very beneficial effect upon these cases of dimin- ished metabolic activity. Given in doses of 1-60 to 1-30 grain, or even more, four or five times a day, boldine seems to have a definite action upon the hepatic func- tions, and, while not increasing the bulk of urine passed, the solids, and in particular the urea, are con- siderably augmented. In addition to this, when possible, a course of physical exercise, either active or passive, should be prescribed. If convenient, the patient may be instructed to walk several miles each day. Breathing exercises, with a view to increasing the lung capacity, are also valuable. These, together with other physical measures, such as hydrotherapy, electrotherapy, etc., ma- terially increase oxidation in the body and assist in no small degree in accomplishing the desired end. Perhaps a few words might be said regarding the conditions associated with low total solids. The normal excretion of urinary solids should be from SO to 60 grams per diem, but there is considerable latitude in these figures, the variation — uually downward — depend- ing principally on the weight of the individual and the amount and kind of food he is taking, a diet low in nitrogenous elements causing an appreciable diminu- tion in the urinary solids. When the solids are de- creased 30 per cent or more, the conditions are serious and it is time to make a careful investigation and follow 190 Essays on Laboratory Diagnosis this with the best treatment possible. While a contin- ued low specific gravity and diminished amount of urine may be entirely functional, very frequently it will be found that this is associated with organic renal disease. Provided this possibility can be eliminated, the treat- ment suggested for the increase of urea will also serve to increase the solids in general. A remedy which is undoubtedly an important factor in raising the amount of solids eliminated is sodium succinate. Five grains taken three or four times a day, alone or with boldine, often will render very effective service. The addition of buttermilk to the diet has also been found to be of value. An excessive degree of urinary acidity is another therapeutic indication which must not be overlooked, since it is an assured fact that many obscure and danger- ous conditions are at least associated with, if not actually due to, dealkalinization of the blood and its etiologic factors. The degree of acidity may be high (the normal varying from 30 to 40 degrees) and yet, owing to, a decreased amount of water passed, there may be a com- paratively normal amount of acid units. (This figure is the relation between the degree of acidity and the twenty-four-hour amount of urine expressed in Cc, and should be about 40,000 in twenty-four hours.) When the degree of acidity alone is increased, the indication for treatment is evident — more water, thus diminishing the concentration of the urine and conse- quently its irritating qualities. Incidentally, it may be The Indications of the Urinalysis 191 stated that no drug will offer better service in conditions of acidemia than plenty of pure water — distilled or car- bonated if so desired. If the acidity is high (the acid- units above 40,000 per diem), it should be reduced as carefully and speedily as possible, and dietetic sugges- tions given which will tend to prevent the further forma- tion of an excess of acids in the body. The diet should be as free from meat as possible, and low in nitrogen. A free use of fruits, both fresh and cooked, as well as vegetables (preferably not dry legumes) and properly- cooked cereals is of value. The "lacto-farinaceous reg- imen" recommended by Combe is excellent. The medicinal treatment of this condition is as nec- essary as it is efficacious. The alkalies (sodium bicar- bonate, potassium or sodium citrate, magnesium carbo- nate, etc.) render excellent service. From 40 to 60 grains of sodium bicarbonate with plenty of water, alone or •combined with suitable eliminants and intestinal anti- septics and given from one to three times a day, as re- mote from meals as possible, may be administered until the acidity has been reduced to normal, the doses then being decreased materially and given less frequently, always keeping the degree of acidity at or slightly lower than normal. Two or three weeks of this treatment will .give eminently satisfactory results in the handling of many chronic conditions that are due to or associated with faulty metabolism and elimination, and which have previously resisted prolonged attempts of treatment by other less definite methods. When alkalies are indi- cated and contipation is present, magnesia may be sub- 192 Essays on Laboratory Diagnosis stituted for sodium bicarbonate with even better results. If, on the contrary, diarrhea is present, lime water in liberal doses (6 to 8 ounces three to six times a day) will be found more satisfactory. Another salt which serves as an excellent urinary antacid and diuretic is potassium citrate. It is compara- tively pleasant to the taste and is not likely to cause gastric irritation ; 20 to 30 grains in water three or four times a day will usually be found sufficient. When the acidity of the urine is steadily lower than normal (a series of several urinalyses is always advis- able) and cystitis or other conditions producing ammoni- acal fermentation and decomposition of the urine are eliminated, the general metabolic activities will usually be found to be considerably below par and the thera- peutic suggestions made previously become of value. These cases very frequently show a marked decrease in the elimination of acid for several days, weeks, or even months, having a periodical "storm" or "crisis," at which time the urinary acidity is tremendous, the gen- eral condition of the patient is serious, and the condi- tions are as completely opposite to the previous findings as could well be imagined. The treatment of these cases is no easy matter, and it is a question whether alkalies should be given or not. At all events, no harm will be done by their judicious use under these circumstances, and, when combined with suitable elimination and stimulation, success will be as- sured. The treatment of those conditions associated with The Indications of the Urinalysis 193 an excessive elimination of ammonia in the urine is prac- tically the same as that of acidemia, since, as has been mentioned before, the high ammonia-index is caused by the neutralization of urea-precursors by the excess of acids present in the body, thus substituting urea with ammonia compounds. The same is true when the so- called "acid bodies of diabetes" — acetone, diacetic acid and oxybutyric acid — are found. The vigorous use of alkalies will give help ; that is, at least temporarily. The indican and the indoxyl group remain to be considered. The detection of indican is a very simple matter, and although its importance per se still seems to be a matter for discussion, its presence, without a ques- tion, is a definite guide to equally definite treatment. Ninety-nine cases out of a hundred evidencing marked indicanuria have associated with them an intestinal dis- turbance of greater or less severity. It is, however, quite possible for serious trouble to be present, and yet no trace of indican be discovered in the urine ; but it is safe to say that whenever indican is found, eliminative and dietary treatment is distinctly indicated, and in direct proportion to the amount of intestinal putrefaction present. In addition to eliminants, of which there are a pro- fusion (calomel in small broken doses still holding its own, saline laxative following it closely, with phenol- phthalein and possibly agar-agar in certain cases), the use of intestinal antiseptics gives valuable assistance. The examination of the urine from an extensive series of cases in which sodium sulphocarbolate (5 to 15 grains, 194 Essays on Laboratory Diagnosis three or four times a day) had been administered, showed a rapid and marked decrease in the fecal putrid ity and the accompanying urinary indican, with a corre- sponding favorable change in the usual unpleasant mani- festations associated with autotoxemia. Another therapeutic method which is now being ex- tensively advocated, and rightly so, is the introduction into the intestine, by the mouth, of cultures of the ba- cillus of Massol — an organism which, in addition to producing an excess of lactic acid, seems to have a defi- nite inhibitory effect upon the putrefactive micro-organ* isms in the bowel. Much is being written on this sub- ject, and it seems evident that this is a therapeutic meas- ure that has come to stay. When the germs are ad- ministered in tablet form, care should be taken to use them very freely — merely one or two tablets every few hours is not enough. On the other hand, if the patient can use milk soured with these tablets, and likes it, this method is an excellent way to secure a large and flour- ishing growth of the "friendly germs" in the bowel. In the treatment of these conditions associated with indicanuria, elimination and intestinal antisepsis are ex- cellent, but they are not enough. The diet should be modified and strict injunctions given to the patient to avoid the hyperproteid diet. The dietary suggestions given previously are of value in these cases; in fact, the so-called "antitoxic diet" is a most excellent adjuvant measure in the treatment of a large number of the chronic diseases. XIX. LABORATORY HELP IN TUBERCULOSIS. Reprinted from THE AMERICAN JOURNAL OF CLINICAL MEDICINE, Chicago, July, 1909. CHAPTER XIX. LABORATORY HELP IN TUBERCULOSIS. Since the discovery of the tubercle bacillus by Koch and the simple methods of staining by Ziehl and Gab- bet's method, the examination of the sputum of sus- pected tuberculous cases has become a routine, and it is rare that a progressive practician attempts to treat a patient without having the laboratory report regard- ing the presence or absence of that bacillus. The stain- ing of the sputum smear has become an absolutely es- sential procedure, and it is not necessary to add that it is both advisable and imperative in the investigation of any patient showing one or more of the cardinal symptoms of pulmonary tuberculosis. In addition to this, however, there are other important phases of the work done in the laboratory which unfortunately usually are neglected by most physicians and which, more par- ticularly, I wish to refer to in this paper. It is well understood that tuberculosis, whether localized in the lungs, a joint, or some other part of the body, is not solely a local disease. Rather, it is always associated with other abnormal conditions of the body, especially of metabolism, and for this reason it is absolutely essential that the general practician should make general and repeated use of the facilities of the scientific laboratory in his routine investigation and treatment of cases of this kind. Thus, the exam- ination of the urine should be made early. Following 198 Essays on Laboratory Diagnosis this a careful examination should be made regularly every third or fourth week. The first urinalysis will point out the general condi- tion of the patient's metabolism, while the succeeding ones will enable one to follow carefully the case, as only in this way can a proper idea of the metabolic activities of the body be gained and appreciated. The physician, by giving his close attention to the findings, will then be in a position to proceed in accordance with the find- ings in the report. The urinary examination should be complete and thorough and not be confined merely to the almost useless tests for albumin and sugar, which, though rarely re- sorted to, seem to be the customary scope of the aver- age "urine examination." The advantage of such lim- ited tests would be noted only in the few cases in which diabetes or Bright's disease were present ; and even then the precipitation of a copper solution does not necessa- rily positively indicate diabetes, nor does the finding of albumin definitely prove the existence of Bright's dis- ease. To be of real service, the examination should at least include quantitative estimations of the normal elements eliminated in the urine, the most important figures of which are the amount, the urea-index, the solids, and the degree of acidity. The examination of a number of specimens of urine from tuberculous individuals shows that the amount of urea eliminated is almost always diminished, and in the majority of cases seriously so. This being true, it is quite easy to understand that in addition to fighting the Laboratory Help in Tuberculosis 199 localized infection, the patient has to contend with the disadvantages of a large amount of effete matter which is not being eliminated from his body in the proper amounts and which consequently either is circulating in the blood-stream or being stored up to produce trouble sooner or later. Dr. Foxhall, in an article recently pub- lished in The Lancet, states that if the average per- centge of urea excreted is below 1.4 per cent for ten or fifteen days it nearly always indicates definite renal dam- age — a condition which cannot be appreciated in time to render any service of value, unless the urine examina- tion has been a routine diagnostic procedure. Another very important finding in the urine exam- ination that has as yet not received the attention it de- serves is the estimation of its acidity. A number of in- vestigations have conclusively shown that an excessive degree of urinary acidity is a very important factor, since it is always associated with certain metabolic dis- turbances which have for their principal manifestation autointoxication, general malaise, indefinite aches and pains, a susceptibility to colds, and a general condition of lowered vitality. This higher urinary acidity probably is due to a condition of alkali-hunger, and evidenced by a marked systemic hyperacidity, or acidemia. We have as yet to learn the exact raison d'etre for this condition, nor do we know positively the exact com- position of the acid substances which may cause this abnormality, but it may be that they are in the same class with the products of proteid putrefaction, such as indican, which is an acid salt — potassium indoxyl-sul- 200 Essays on Laboratory Diagnosis phonate. Indicanuria is frequently found associated, with intestinal putrefaction, but may also be found m cases exhibiting proteid putrefaction, in other parts of the body, as for instance, empyema, large tuberculous lesions, etc. The examination of the urine for acidity should be carried out in the routine of every case. More particu- larly is this imperative in the investigation of those suf- fering from tuberculosis, for in addition to fighting the local infection, the diminished degree of alkalinity of the blood renders that fluid less resistant, diminishes its capacity to carry oxygen, and generally devitalizes the cells that are nourished by it. The employment of the litmus test is most unsatis- factory, and it should, therefore, be entirely discarded; neither is the examination for acidity of a single voiding of urine of much value, as the degree of urinary acidity varies greatly from time to time, depending upon the relation between the time of urination and alimenta- tion, and also whether the specimen is passed in the evening or in the morning. For this reason care should be taken to instruct the patient as to how to obtain a complete twenty-four-hour specimen of urine, and after the total quantity has been carefully noted a portion from the well-mixed fluid may be set aside for an early examination. Provided this is done, the normal degree of acidity should range between 30 and 40 degrees, and the number of acid-units (the relation between the de- gree of acidity and the amount of urine passed) should extent. Laboratory Help in Tuberculosis 204 be about 40,000. This represents about 1,300 Cc, or urine with an acidity of 30 degrees, or 1,000 cubic centi- meters of urine with an acidity of 40 degrees. If the acidity proves to be very high — and this only too often is the case — it should be promptly reduced by the administration of suitable alkaline remedies. On the other hand, if the acidity is markedly diminished, the possibility of cystitis or other conditions usually asso- ciated with fermentation of the urine should be consid- ered; or, if these are not the cause of the low degree of acidity, then the emunctories should be thoroughly stimulated in order that the acid substances which evi- dently are being stored up in the body may be neutralized in the cells or, allowed to be eliminated in the usual way. It has been found that if conditions showing a dimin- ished urinary acidity are allowed to persist for any length of time, it is quite frequently followed by cer- tain "crises" which are not only decidedly inconvenient to the patient, but often dangerous. A good deal more stress should be laid upon the find- ings in the feces than now is the case. One of the fre- quent occurrences associated with pulmonary tubercu- losis is tuberculosis of the intestine, or at least a mark- edly disturbed functional condition of this organ. An ■examination of the stools, in addition to showing the digestive capacity of the intestinal juices, and also the absorption by the villi, gives one a very good idea of the extent of the putrefactive changes which are usually present, as well as whether infection of the bowels by an abnormal bacterial flora is present, and if so, to what •extent. 202 Essays on Laboratory Diagnosis Unfortunately, the fecal analysis is but rarely made, except in large hospitals or institutions. Its routine use would be attended with more success in practice, as un- doubtedly the information gained by such examination would give pointers of distinct value in the treatment of the abnormal local conditions so frequently associated with tuberculosis. One of the most important things that is necessary for the physician to do in the home treatment of tuber- culosis is to give careful attention to the digestive appa- ratus, for the reason that one of the important factors in the treatment of tuberculosis seems to be the neces- sity for hyperalimentation. If the capacity of the stom ach to digest food is diminished or impaired, this mat- ter should be appreciated at the earliest possible moment in order that proper steps may be taken to remedy this condition. Stomach analysis offers a solution to many of these difficulties, and it is distinctly advised in every case of pulmonary tuberculosis associated with digest- ive disturbances, provided, of course, there is not se- vere asthenia and any of the few conditions which neces- sarily contraindicate the employment of the stomach- tube. The examination, of the urine always, and of the feces and gastric contents when necessary, together, of course, with the frequent bacteriologic examination of the sputum, will do much to enable the physician to practice better medicine in general and to obtain better and more satisfactory results in the treatment of this- disease in particular. XX. THE URINE IN TUBERCULOSIS. Reprinted from THE MEDICAL STANDARD, Chicago, April, igio. CHAPTER XX. THE URINE IN TUBERCULOSIS. In the treatment of tuberculosis we have a great and by no means easy problem to handle, and because of this we need every resource that science can afford or that research can secure. Among many procedures there is one — the examination of the urine — which will give us help that may lead to a more successful out- come of our efforts, and for this reason it should, I firmly believe, be given much more credence and atten- tion. It is generally understood that tuberculosis is not simply a condition in which some part of the body has been invaded by the tubercle germ, but rather that it is a general condition of lowered resistance with the addi- tion of a localized focus of infection. It will be found on careful investigation that practically every tubercu- lous individual shows a marked depravity in the meta- bolic activities of their bodies. Since the metabolism plays such an important part in both disease prevention and cure, it would seem that a knowledge .of just how well these processes were be- ing carried on and to what extent deficiencies or dis- turbed relations are present, might be of much assist- ance to the physician that may be directing the fight against this widespread and terrible disease. Physiological chemists, by their studies of the inner 206 Essays on Laboratory Diagnosis workings of the body, have demonstrated that the true urine shows, as does no other analyzable body fluid or secretion, the true state of the metabolic equilibrium. In addition to giving information regarding the func- tion of the kidneys and the conditions present in the whole length of the urinary tract, the constituents of the urine and their relations to one another and to the nor- mal, are as perfect a mirror of the cellular activities of the body as we can hope to find. This being the case, it must be plain that in tubercu- losis, as in all other perverted states, *'. e., in all general disease processes, the examination of the urine is not only a valuable adjunct, but an essential. Unfortunately, there is still a wide variance of opin- ion on this subject, and by no means all are in accord with the above statements ; but the fact, however, re- mains. The more study that is given to this subject, the more definitely will it appeal to the student as be- ing both right and proper. A careful investigation of a number of tuberculous individuals will quickly con- vince the skeptic and encourage the doubting. It is admitted that there are several other clinical laboratory procedures that are now well engrained in the medical constitutions of the progressive physicians. Principal among these are the various tuberculin reac- tions, of which the Moro or von Pirquet tests are probably the best, and the examination of the sputum for tubercle bacilli. The opsonic index may or may not be of value; one thing is certain, no matter whether it can be invariably accurately made or not, that it is a The Urine in Tuberculosis 207 physical impossibility for the general practitioner to make this test, and for this reason it must be ruled out, at least for the present. The urine examination, on the other hand, is easily and accurately made by any man that is willing to de- vote as little as ten or fifteen minutes of his time to this work. The equipment needed is comparatively slight, and with a little experience any physician can make a very creditable and extremely valuable analysis. Just what the varied findings mean is not as fully ap- preciated as might be, and because of this there is still a lack of interest in this subject. However, it is to be hoped that during the next few years a wide and ever- increasing interest will be aroused, and that, as a conse- quence, much more light will be thrown on this and allied subjects. One of the disorders most frequently encountered is a diminution in the normal amount of urinary solids passed in tweny-four hours; of these, of course, urea is the most important. Just why this should be so is still a matter of conjecture, although several very plaus- ible reasons have been advanced. At all events this con- dition is not necessarily a sign of definite kidney change, as has been stated by some. The diminution in the amount of urea excreted may be due to a decrease in the normal blood alkalinity, the urea-precursors being used up and eliminated as am- monia compounds. Again, the generally lowered vital state may serve to prevent the elimination of the nitrog- enous waste already present with a resulting increase 208 Essays on Laboratory Diagnosis in the toxicity of the blood and the body fluids. As a matter of precaution, it must be remembered that since the urea-index is an excellent guide to the proteid me- tabolism, the figures obtained will receive their proper value only when a general idea is gained of the amount of nitrogenous food ingested. For this reason, in the tuberculous state the usually decreased urea-index is in some cases often masked by the tremendous excess of urea resulting from the forced feeding of eggs and milk which is still altogether too commonly used. It might be added that if the urea-index is above 3 per cent, or, say, 30 grams, in twenty-four hours, that the indication is to diminish the proteid ration. The results of a number of urinalyses made in the early tuberculosis state show that when the ordinary diet is taken, the urea is diminished usually from 75 to 200 per cent, averaging, perhaps, one-half the normal. The calcium content of the urine of tuberculous pa- tients is practically always increased. Senator, the fa- mous German clinician, having proved this over thirty years ago. This is an interesting fact, and it is unfor- tunate that the procedure necessary to determine this factor is so tedious and complicated, for were it reason- ably simple we might find in the calcium-index a guide to the proper administration of calcium' wherewith to balance this excessive loss. On the other hand, it has been found that the elim- ination of phosphates is considerably below the normal, and it has been suggested that this may be due to a dis- turbance in the metabolic equilibrium presided over The Urine in Tuberculosis 209 directly by the nervous system; in other words, a nerv ous disorder. Dr. J. Henry Dowd, of Buffalo, has done some interesting and original work along this line, and concludes that the phosphatic index is of ex- treme importance, serving to point out serious meta- bolic faults in their earliest beginnings. The estimation of the urinary acidity in the tuber- culous is a matter that will give the investigator much food for thought. It is believed that a study of this subject alone, with its relation to blood alkalinity and the various associated conditions, will prove of immense value in forwarding the combat now being waged against tuberculosis. It is still supposed by some that this test is of little or no value, but in spite of this it has been found of inestimable service, and I have no hesita- tion whatever in stating that this procedure should be carried out in the routine of every urine examination. It has been conclusively shown that an excessive de- gree of urinary acidity is a very important factor, since it is always associated with certain metabolic errors which have for their principal manifestations autoin- toxication, general malaise, indefinite aches and pains, a susceptibility to colds and various infections, an'! a general condition of lowered vitality. This highei urinary acidity is probably due to a condition of alkali- hunger, and evidenced by a marked systemic hyper- acidity or acidemia. This test will be found to be particularly useful in tuberculosis, as a check on the alkalinity of the blood is of importance, for upon this factor depends the ca- 210 Essays on Laboratory Diagnosis pacity of the phagocytes to carry on their fight, and if there is an excess of acid-substances in the blood, that fluid must of necessity be much less resistant to disease, owing to its diminished capacity to carry oxygen. The inevitably decreased interchange of gases and the con- sequent loss of vitality of every microscopic cell-struct- ure is of prime importance and a matter that should not be overlooked. It must be remembered that there are several ex- traneous factors, such as cystitis or retention of urine, or, for that matter, any circumstance which tends to promote alkaline fermentation, which will materially modify the findings, and for this reason should be reck- oned with, and, if possible, guarded against. Another abnormal finding frequently seen in the urine of the tuberculous is indican. The test for indi- can is an important one and should be made in each urinalysis, preferably quantitatively. Personally, I am willing to commit myself by unqualifiedly saying that indican in more than the merest trace is evidence of a pathologic condition which requires attention. The contention of some that indican itself is non-toxic and that it is usually present in the urine of meat-eaters, does not alter the fact that the conditions associated with indicanuria are decidedly detrimental to those sup- posedly in the best of health, and, of course, doubly so to those burdened with the presence of an active tuber- culous lesion. Indicanuria is not only found associated with intes- tinal putrefaction, but may also be found in cases exhib- The Urine in Tuberculosis 211 iting proteid putrefaction in other parts of the body, as, for instance, empyema, large tuberculous lesions, etc. Another substance closely allied with indican is in- dolacetic acid, and it might be well to make a test for this as a routine. It is a very easy procedure, consist- ing simply of acidulating a few cubic centimeters of urine with an equal volume of hydrochloric acid and adding one or two drops of a 1 per cent solution of potassium nitrite. A slight pink coloration is a positive test. Little needs to be said of the Diazo-reaction of Ehr- lich, as it is a procedure of comparatively slight value. Its disadvantages lie in the fact that it is not con- stantly found in any condition, and it may be found in several widely different diseases. It may be of some corroborative value in the diagnosis of suspected ty- phoid fever, and it is true that it is sometimes found in the acute miliary form of tuberculosis, but still its diagnostic value is decidedly limited. A French investigator has recently suggested that there may be certain definite substances passed in the urine of the tuberculous which prevent alkaline fermen- tation. He keeps specimens for several days or even weeks, testing the acidity from time to time. This is hardly a practical proposition in general practice. How- ever; it is quite possible that future investigators will find some urinary test which will be as definite and ac- curate as the tuberculin reaction, but as yet this is a task for the research man. The presence of albumin, bile, blood, pus and other pathologic elements should warrant the same attention 212 Ess»ys on Laboratory Diagnosis as though found in any other disease. Their signifi- cance is probably of no greater import in tuberculosis, pointing as they do to disturbances which require the same care as under other and different circumstances. In closing, it might be well to add that as a guide to the proper dietetic management of individuals suf- fering with tuberculosis the examination of the urine stands pre-eminent. The comparatively small amount of bother involved is more than balanced by the in- creased measure of success which results from careful and accurate work. The finding of an increased urea- index, an excess of chlorides or urates, indican and it£ congeners or an excessive degree of acidity are all points of importance, and, rightly appreciated, should serve as a stimulus to radical reforms in the diet and general hygiene. XXI. CONCLUSIVE RESEARCHES IN METABOLISM. (A paper read before the American Association for Clinical Research, Boston, September, 1910.) Reprinted from THE LANCET-CLINIC, Cincinnati, November nth, 1910. CHAPTER XXI. CONCLUSIVE RESEARCHES IN META- BOLISM. My interest in clinical research work ends just as soon as it gets beyond the possibilities of the capacity, time and facilities of the general practitioner. One of my great aims is, in my small way, to stimulate a greater interest amongst the rank and file of the profession in the simple laboratory work which is not only the most helpful in the routine of general practice, but absolutely essential to the proper investigation of every case com- ing to the physician for help. I want to impress upon the members of the Amer- ican Association of Clinical Research here assembled, that the several "Conclusive Researches in Metabolism" to which I shall briefly refer in this paper are none of them so tedious or complicated that they cannot be carried out by any physician anywhere. There is a mistaken idea that is unfortunately quite prevalent that the investigation of the chemical cell ex- changes of the body is only called for in the study of certain more or less defined disorders of metabolism. All too often the "research" consists in a few questions, a cursory examination and, once in a while, an "exam- ination of the urine" which really is nothing more than a farce and to all intents and purposes useless and a waste of time. I confess that this is a strong state- ment, but, nevertheless, you all can testify to its truth. 216 Essays on Laboratory Diagnosis Thousands of practicing physicians in this day of progress seem: to have a mistaken idea that research work is only for the research laboratory and entirely out of their reach. There could be no greater fallacy. One cannot too often reiterate, or too thoroughly im- press the fact that upon the much neglected factor of the metabolic cell exchanges carried on in the system hangs the inception and progress of a goodly share of all disease, as well as its prevention and ultimate cure. Upon what is the so-called vital resistance depend- ent if not upon the important changes ever going on in the millions of minute body cells? This being grant- ed, should not the study of the metabolism be made the most important part of the investigation of every individual consulting us, regardless of their several and widely different ailments? By far the largest amount of information regarding the metabolic activities of the body may be learned from the careful urine examination. It is granted that other and more complicated procedures may be attempted, but these lead us beyond the confines of the work of the average physician, and for this very reason will not be mentioned here. I like to repeat as often as possible a more or less axiomatic statement: "There is no one diagnostic procedure which gives us so many and so varied therapeutic pointers as does the urinalysis." I think that you will all agree with me that this is true. The most important urinary findings are not albu- men, sugar, casts, or any of the more common abnor- mal substances for which we have all been so thoroughly Conclusive Researches in Metabolism 217 taught to look. These findings cannot give us nearly as much therapeutic information as several others of which I shall now speak — and this for the simple rea- son that they are usually evidences of definite organic disease conditions which, it is well known, are by no means easily handled. In other words, the abnormal urinary findings — albumen, sugar, casts, etc. — are re- minders that our study of the patient has been made rather late in the day. In my estimation, the most important urinary find- ings are those which cast a light on the inside working? of the human machine ; in other words, the quantitative estimations of the several normal wastes which are eliminated in the urine. Chief amongst these are the urinary acidity and the solids — urea, of course, being the mlost important one. As I have stated elsewhere, the urinary acidity is a factor of prime importance in the study of any disease condition; yet, in spite of this, its value to the clinician has been persistenly overlooked. It is still the excep tion rather than the rule to estimate the degree of acid- ity in every case, and if, perchance, a test is really made, the old-fashioned litmus test is usually all that is at- tempted. No more conclusive evidence as to the proper car- rying out of normal metabolic functions, or not, as the case may be, can be learned than from this simple and easy test alone. Let us for a few mtoments consider what the variations in the urinary acidity really mean. Eliminating the changes in the acidity due to extrane- 218 Essays on Laboratory Diagnosis ous circumstances such as the retention of the urine, fermentation and its modification by drugs, we can read- ily understand that this factor must give us a definite idea of the alkalinity of the blood. As a matter of fact, the test for urinary acidity, because of its convenience and simplicity, supersedes absolutely the estimation of the alkalinity of the blood. I need hardly emphasize the immediate clinical im- portance of this factor in diagnosis, prognosis and treat ment. You will recall that upon the presence of free alkali in the blood-plasma depends one of its most im portant functions, viz., oxygen-exchange. And what does not. depend upon the oxygen-carrying capacity of the blood? Here we have a matter of such far-reach ing interest to every practitioner, no matter what may be his creed or specialty, that too much can hardly be said to stimulate more interest in its study. Not only should the foregoing be taken into con- sideration, but one may with much advantage consider more carefully the influence of hyperacid urine upon the kidneys and urinary tract. It is not difficult to im- agine that the irritating qualities of urine vary directly with its acidity. And this fact is demonstrated daily with unerring accuracy. Two years ago I found that many cases showing an excessively high acidity showed hyaline casts and other evidences of irritation. Now comes a prominent German investigator with the state- ment that all albuminurias should be discounted until the urinary acidity has been made normal in vivo. Much more might be said regarding the influence Conclusive Researches in Metabolism 219 and importance of the urinary acidity; but this will, I hope, be worked out in the daily routine of every mem- ber present, and I can assure you that the work carries with it an intense interest and possibilities for results that cannot for one moment be gainsaid. Another urinary finding which is also of much value, but which, probably because of its imjportance, has been persistently overlooked, is the ammonia-index. Physio- logical chemistry explains to us the "why" of ammonia elimination, and without going into details, we believe that the ammonia-index is closely related to the acidity and serves to show us just how well the human econ- omy is handling the excess of acid substances which get into the blood stream. Why, may I ask, should am- monia estimations be so closely confined to the study of diabetic urines? Are there no other acid bodies in the blood save acetone and diacetic acid? Is not indican an acid body? And diacetic acid? And, for that mat- ter, several other unknown products of intestinal putre- faction ? One would suppose that the importance of the urin- ary solids would be considered more often than is the case. The evident importance of their quantitative esti- mation is appreciated by the majority, but one small factor practically puts a study of the solid-index, or, better still, the solid-indices, out of the question for most physicians. It necessitates the procuring of a full twenty-four-hour specimen, which in the majority of cases seems too difficult to explain, or too much trouble to cause the patient. Rightly speaking, no urinary test 220 Essays on Laboratory Diagnosis should be made save from the full twenty-four-hour amount. Some will not fully agree with me; but when one is studying the metabolism none can deny that my contention is right. A urine examination without a quantitative urea test is not very much good. The variations in the urea- index alone are often sufficient to lead to a definite diag- nosis and effective treatment. The relation of the urea to the acidity and ammonia is very close; for it so hap- pens that the alkaline urea-precursors are, to a certain extent, used up in nature's attempt to maintain the blood alkalinity at normal. So we are justified in expecting that with a high acidity one will more often than not find high ammonia and low urea. The other solids, most important among which are the chlorides and the phosphates, should also be con- sidered. Very frequently the chloride-index will ex- plain the reason for an intractable hyperchlorhydria ; and the reduction of this figure to normal will cure the trouble. It must be remembered that the chloride-index is a very indefinite factor simply because it varies so much with the intake of common salt. The elimination of phosphates evidently has some relation to the nerv- ous system, and Dowd, of Buffalo, has done some ex- cellent work which goes to prove, as he says, that the phosphatic index is the pulse of the nervous system. Hours could be well and profitably spent in discuss- ing many interesting points that are closely related to this subject. The relation of indican to the urinary findings is of itself a subject for much thought. Many Conclusive Researches in Metabolism 221 hundreds of analyses have proved conclusively that indicanuria has an influence in the causation of acide- mia, and with it the diminished oxidation and elimina- tion which is always associated with this important and much neglected condition. In closing, let me express the hope that the con^ tinued reiteration of the fact that the general prac- tician must eventually realize the need for the study of the metabolism as one of the first elements in the suc- cessful treatment of all disease will some day bring with it a revival of note; and if this happens, I am confident that with- this revival will come more effective service, increased professional reputation and better re- muneration for our work. XXII. INDICAN FROM THE STANDPOINT OF THE GENERAL PRACTITIONER. Reprinted from AMERICAN MEDICINE, New York, December, 1910. CHAPTER XXII. INDICAN FROM THE STANDPOINT OF THE GENERAL PRACTITIONER. Of all the urinary tests that have come into more gen- eral use during the past five years, that for indican seems to have taken a firmer hold on the average general prac- titioner than any other, and has received much promi- nent mention in the medical literature. The interest in this particular urinary finding is still growing, and right- ly so, for undoubtedly the presence of indican in the urine is a clinical factor of no mean importance and is deserving of the consideration of every practitioner of medicine. The test is not difficult and takes but a few moments, and for these reasons is strongly urged on those physicians who may not as yet be in the habit of performing this test in their regular routine. It is generally understood that the presence of more than traces of indican in the urine is caused by the putrefaction of proteid foodstuffs in the intestinal canal, and this is undoubtedly the principal cause of this con- dition. It must be remembered, however, that the ab- sorption of the products of proteid decomposition any- where in the body will produce indican in direct ratio to the amount of pus present and the conditions permit- ting its absorption. For this reason the possibility of the presence of such complications as empyema, bronchi- ectasis, and other conditions in which there is an ex- 226 Essays on Laboratory Diagnosis often the case in tuberculosis; but, too unfortunately, patients under treatment are usually taking altogether too much proteid food with the almost inevitable accom- panying indicanuria. The basic cause for the more or less complex combi- nation of circumstances with which indicanuria is prac- tically invariably found, is believed to be due to three important factors: 1. Rapid and excessive, eating of a diet overrich in proteid ; 2. A lack of muscular tone in both the intestinal and abdominal walls; and 3. Disturb- ances in the normal secretory functions of the intestinal glands due, in all probability, to the toxemia caused by the motor insufficiency. Some investigators have called attention to the fre- quency with which indicanuria is associated with hypo- chlorhydria. Simon, of Baltimore, even suggests that the degree of gastric acidity may be judged by the amount of indican present in the urine. This may or may not be; probably other factors have more to do with this. It will be not uncommonly noted that patients suffering with hyperchlorhydria often show large amounts of in- dican. Simon himself reports having found it several times in gastric ulcer, with which condition an excess of acid is practically a constant finding. Unfortunately, when much was being said and written regarding the clinical value of indicanuria, several promi- nent clinicians belittled the importance of the test, said that indican was normally present in the average indi- vidual and threw cold water upon the enthusiasm of many who believed that they were learning to appre* Indican in General Practice 227 ciate something that would b© of real help to them in their work. Such statements are not borne out by the extended clinical experience of the majority; and the writer believes that although indican may be present in decidedly appreciable amounts in so-called "normal" urines, it is far from a normal finding and its presence should be an indication for prompt therapeutic action. It is a rare thing for a dentist to find an absolutely good set of teeth, neither is it common to find perfectly working functions in any individual. The average is decidedly below what we know must be a proper stand- ard; and because of this we cannot surely consider it normal for a person to have dental caries or indigestion. Nor, then, should we be deceived by statements to the effect that indicanuria is so common that it is "normal" and, consequently, a negligible factor. Granted that there is a need for the test for indican, how can one best perform it ? In order that the general practitioner can be converted to the need for any addi- tional work it must be made plain to him that the work is going to be of real value to him and he must be shown the easiest and simplest way. So many tests for indican have been suggested that one is tempted to believe that there is no satisfactory one. Practically all tests de- pend upon the fact that the colorless indican — potassium indoxyl sulphonate — can be oxidized into the blue indigo by various agents in the presence of hydrochloric acid. The first oxidizing agent used by Obermayer was ferric chloride and a solution of two pro mille of this salt in hydrochloric acid is the commonly used reagent that 228 Essays on Laboratory Diagnosis bears his name. Now, however, other oxidizing agents are superseding ferric chloride, simply because the Ober- mayer reagent is often found to contain sufficient free chlorine to vitiate the test; for it is well known that chlorine is one of our best bleaching agents and if al- lowed to decolorize the indigo it would lead to erroneous conclusions. It may be of value and interest to relate here an in- cident told to me by my friend Dr. Clifford Mitchell of Chicago. The doctor in his work ran across a specimen of urine showing an excess of indican and laid the re- mainder of the specimen aside to take to college that afternoon to demonstrate to his students. When the time for the test arrived, the reagents were added and the attention called to the "beautiful blue color" which, strange to say, was entirely lacking. The test was re- peated only to corroborate the previous finding. The bottle was then carefully scrutinized and was undoubted- ly the specimen which in the morning had showed such an abundance of indican. On returning to his office Doctor Mitchell made still another test and a deep blue color resulted. Evidently the trouble was with the re- agents, and investigation showed that the hydrochloric acid used at the college was not chemically pure, al- though supposedly so. It contained quite a large amount of free chlorine. This little incident is related here to emphasize a fact which I have since found out was true. From it one should learn that a variation in reagents may vitiate an indican test and that one of the essentials is to have Indican in General Practice 229 "chlorine free hydrochloric acid." It might be added that if Obermayer's reagent is used it should be made comparatively fresh for the same reason. Amongst the other oxidizing agents which one may use in the indican test are potassium chlorate, chloride of lime, potassium permanganate, ammonium persulphate, osmic acid, sodium perborate and hydrogen peroxide. I have found the last mentioned reagent to be very satisfac- tory and practically always use it in my laboratory. It is very convenient, for not only is it used in general office work, but it happens to be used in at least two other laboratory tests and thus reduces the number of reagents, bottles and space required. My most satisfactory routine is as follows: To five cubic centimeters each of urine and pure hydrochloric acid add two cubic centimeters of chloroform and one or two drops of peroxide of hydrogen. On shaking, the blue color due to the liberated indigo will be seen in the choloroform which settles to the bottom of the tube. Frequently the coloration of the chloroform is very slight, while the supernatant fluid is dark in color. The addi- tion of two or three cubic centimeters of alcohol — 70 per cent is perfectly good enough — and slight shaking will dissolve all of the indigo in the alcohol-chloroform mixture and give a much more satisfactory test. Frequently on shaking the mixture the chloroform settles in the form of an emulsion and the blue color is not as easily detected or measured. To obviate this Ober- mayer suggested that the precipitation of the substances which caused this trouble be accomplished with a solu- 230 Essays on Laboratory Diagnosis tion of lead acetate. After the addition of this reagent and filtration the nitrate is tested as above. Mitchell in a splendid paper entitled "The Difficulty of the Test for Indican in Urine" (New England Med- ical Gazette, October 1910) advises the . following pro- cedure: To ten c. c. of urine add six drops of "clear" twenty per cent solution of lead acetate (not sub-acetate, nor basic acetate), mix well and filter. To the filtrate add equal parts of Baker and Adamson's hydrochloric acid of a specific gravity of 1.19. Mix well, warm the mixture to between 105 and 115 deg. F., then add care- fully, without shaking, one drop of a weak bleaching powder solution, warm again and add a few drops of chloroform, warm again and so on until two c. c. of the chloroform have been added. Then shake vigorous- ly. A clear blue at the bottom shows a successful test, but many bubbles or a whitish emulsion shows that not enough lead acetate was used. Only an intense blue color is to be regarded as clinically significant. It must be evident that it is advisable to record the progress of an indicanuria, and for this reason some sort of a quantitative test is advisable. There are sev- eral quantitative methods, most of which are altogether too tedious for use in general practice. The oxidation of the indican to indigo in a large amount of urine, say 500 c. c, and its abstraction by chloroform, with subse- quent drying and weighing is a test that is quite out of the question. The use of a standardized decolorizing solution is rec- ommended by Boardman Reed and for this purpose a Indican in General Practice 231 solution is used which contains one per cent of free chlorine (3.46 gms. of potassium chlorate in 100 c. c. of distilled water). After the test is made one adds the above solution drop by drop, shaking between each addition. The resulting figure is expressed as the num- ber of drops of the bleaching solution that are required to decolorize the indigo. Two drops is supposed to be sufficient to decolorize the indican normally present. In this case, or for that matter any other, it is essential that definite amounts of urine and all of the reagents are used and for convenience I suggested several years ago the use of a specially graduated test-tube (since called an "Indicanmeter") which materially facilitates this. This is an important point — the same amount must be always used if the tests are to be compared with one another or any standard. For routine use this decolor- ization test, which is usually called Robin's test, is a good one; and to those who are willing to spend five or six minutes in carrying it out, it is warmly recom- mended. The usual method is to roughly gauge the amount of the blue coloration and record it as zero, trace, large trace, excess, etc. In the brief article describing the above tube I referred to the possibility of producing an indican test-scale similar in character to the hemoglobin scales of Tallquist, Niemoeller or Hall. Since then two or three color-print scales have been produced, the best of which is incorporated in Dr. F. A. Faught's excellent little book "Essentials of Laboratory Diagnosis" which the writer here takes the opportunity of recommending 232 Essays on Laboratory Diagnosis very highly. Folin has called attention to the fact that the color of a fifty per cent dilution of Fehling's solution (vol- umetric) is practically the same as that of an indican test where twenty milligrammes were found in 1,000 c. c. of urine. Basing this color as a standard, a series of dilutions may be made which may serve as an indican color scale. Unfortunately, there is a tendency for the copper in the solution to deposit itself on the tubes so that after a few weeks their value is lost. A really sat- isfactory printed indican test-scale showing the approxi- mate amounts of indican in milligrammes per liter has yet to be made, but will doubtless be published before long. Occasionally the choloroform after a test is colored red instead of blue. This is usually due to a preponder- ance of skatol products instead of indol products with a clinical significance practically the same as the blue indican. If the patient has been taking potassium iodide the red color will be due to iodine. It will quickly dis- appear on adding a drop of a saturated solution of so- dium hyposulphite (the ordinary "hypo" of the photog- rapher). Askenstedt of Louisville believes that the red or the blue color prevails in accordance with the tem- perature of the mixture and for this reason always brings his mixtures to a definite temperature before noting end results. Bassler in a recent contribution entitled "Red indican Urine: Its Significance" (Monthly Cyclopedia and Medical Bulletin, October, 1910) states that : "It is interesting to observe that while both indicans are found Indican in General Practice 233 in cases of albuminoid putrefaction in the intestines, urorosein (red indican) is more commonly found where there is putrefaction of vegetable substances, as in the cases of saccharo-butyric chronic intestinal putrefaction. "The blue indican cases usually present themselves clinically showing depression, relaxation, lowered vital- ity and persistent anemia. The red indican cases, on the other hand, are more usually of the irritative, anxious, highly neurotic and hysterical types, with good general body and blood conditions and are not so commonly con- stipated. * * * It is an almost daily observation with me that when the proper diet for an indican case has been maintained for a while (essentially proteid free) and the output of indican has been lowered, the individual will develop into a urorosein case for which the diet would be essentially proteid in make-up." An easy associated test which may be quickly made in conjunction with the indican test is that for indol- acetic acid, another product of intestinal putrefaction «ither identical with urorosein or the so-called "red in- dican" or at least very closely allied to it. So far as my experience goes, both tests may be made on the same specimen without difficulty. BQerter suggests that to five cubic centimeters each of urine and HC1 one drop of a 1 per cent solution of potassium nitrate be added. If urorosein is present a rose pink coloration will ensue, the depth of the color being dependent on the amount of indolacetic acid present. The indican test may then be continued by the addition of the chloroform, hydro- gen peroxide, etc. To save multiplication of reagents 234 Essays on Laboratory Diagnosis the half per cent solution of sodium nitrite (used in Ehrlich's diazo-reaction) may replace the potassium ni- trite solution, two drops being used. Indolacetic acid may often be present in comparatively large amounts when the test for indican is negative. The two substances are evidently formed independently of one another and either or both may be present in any case. As Bassler suggests in his article (quoted above) there may be a variation in the kind of material that is undergoing decomposition and this be the expla- nation. At all events, both substances are indications for very nearly the same routine treatment. The examination of a large number of specimens has convinced me that when one finds a urine containing indican in excess, that in all probability there will be quite a definite sequence of associated findings. With- out making too positive a statement (for every rule has its exceptions) I believe that indicanuria is commonly associated with the following disturbed relations in the urinary findings: 1. An excessive degree of urinary acidity; 2. A high ammonia index; 3. Diminished out- put of urea, and 4. A frequent lowering of the total solids (in addition to the low urea-index). It will not be my intention to go into the details and explain the philosophy of these findings, save to add the suggestion that the circumstances which favor the production of indican, also favor the production of other acid bodies, as yet unknown, which diminish the normal blood alka- linity and cause complications which are by no means thoroughly appreciated. Hence it would seem that if Indican in General Practice 235 the most is to be gained from the urine examination, when indican is present in excess, make special note of the other findings suggested above. The presence of a decided indicanuria is rarely not accompanied by other symptoms. In a few cases the patients are sure that "there is nothing the matter" with them, but more often there is a combination of un- pleasant symptoms, prominent among which are head- ache, migraine, malaise and drowsiness, a noticeable diminution in the capacity for work — both mental and physical, chronic constipation and indigestion, nervous irritability, fleeting pains and, often, insomnia. Anemia is very commonly found in these cases, and it is often surprising with what a bound both the red-count and the hemoglobin will rise when the toxemia is removed and indican disappears. It has been frequently noted that the severe anemias, chlorosis and pernicious anemia, are associated with indicanuria; and considerable help may follow the efforts made to relieve this condition. The treatment of indicanuria per se is no sinecure — it is far more than the simple unloading of the bowels and the removal of the putrefying material therefrom. Indicanuria is a habit, and the system has to be weaned from it. The first thing to do, of course, is to judiciously use the purge. Dietary regulation with a decrease in the proteid intake (especially the animal proteids) and an increase in the time taken to chew the food. Metchni- koff's bacterial therapy has proved itself of some value. Soured milk is much better than tablets of the germs. 236 Essays on Laboratory Diagnosis Colonic irrigations are splendid and should be carried out daily whenever possible in every case. From one to three quarts of water at 80 to 90 degrees should be allowed to slowly enter and leave the colon as high up as possible. This may be continued daily for a week or longer. Another very valuable measure is the high oil injec- tion. From two to six ounces of cotton-seed or olive oil may be injected as high up as possible and retained all night. I have found that the addition of one or two per cent of ichthyol to the oil is an effective addition. This may be repeated once or twice and special atten- tion given toward dislodging any particles of impacted feces at the angles of the colon. The relief of ptosis of the abdominal walls and viscera is another important essential. In a paper entitled "In- dicanuria and Enteroptosis" (Am. Jour. Physiologic Therapeutics, May, 1910) the writer called attention to some special work that had been done along this line. Frequently when this is borne in mind persistent and intractable indicanurias disappear altogether, to stay away as long as the ptosis is relieved. There is a great deal of thorough helpfulness in this indican question and it is believed that further work by the general profession who bear this fact in mind will do much toward simplifying diagnoses in the "compli- cated cases" and making the treatment more direct and efficient. It should be added here in closing that preserved urines do not always give good indican tests. For this Indican in General. Practice 237 purpose formalin at least should never be used. Patients using urotropin or hexamethylenetetramine and iodine compounds should not take them for several days prior to the test. XXIII. INDICANURIA AND ENTEROPTOSIS. Reprinted from THE AMERICAN JOURNAL OF PHYSIOLOGIC THERAPEUTICS, Chicago, May, 1910. Copyright, 1910, by Henry Robert Harrower. CHAPTER XXII J. INDICANURIA AND ENTEROPTOSIS. The work of the clinical laboratory is not infre- quently of great assistance to the physician in empha- sizing the necessity for giving special attention to cer- tain conditions which, without the valuable guidance of the laboratory findings, might otherwise have been entirely overlooked. For this reason it is always ad- visable, when consulted by an individual for the first time, to see to it that a specimen of the urine is prop- erly collected and examined as soon as possible. With the report of this examination at hand one is in a bet- ter position to find out the disease conditions as they really are. One of the most frequent abnormal urinary findings is indican in excess. Considerably more than half of all the hundreds of specimens that have passed through my laboratory have shown the presence of indican in varying quantities, usually, however, in very evident amounts. That this is a mere coincidence cannot for one moment be considered. Many other investigators will corroborate the fact that indican is one of the most commonly found abnormal substances in the urine. Be- cause of this, some have gone so far as to say that indi- can is normally present in the urine of the omniverous human. This is not true. The ideas of those medical men who still consider indican to be of little or no real clinical significance 242 Essays on Laboratory Diagnosis are, to my mind at least, sadly at fault. The fact that indican itself happens to be a non-toxic substance proves nothing. Without a doubt the presence of indican is evidence of the coexistence of other substances man- ufactured simultaneously. The presence of these toxic bodies in the blood is unquestionably harmful. Be that as it may, the careful investigator quickly accustoms himself to look for certain physical findings accompany- ing certain of the urinary findings, which his clinical ex- perience has shown him to be frequently associated with one another. It will not be my object here to discuss these various findings in detail, but rather to call par- ticular attention to a clinical combination which investi- gation has proved to be much more common than has ordinarily been supposed. The examination of a large number of specimens of urine, coupled, in many cases, with a careful examin- ation of the abdomen and its contents, leads me to be- lieve that enteroptosis is very often closely associated with the finding of indican in the urine. It would not be proper to construe this as a hard-and-fast rule, nor would it be either consistent or scientific to say that the majority of those showing an indicanuria are suffering from prolapsed viscera; but from my own experience I am led to believe that this condition, or, rather, com- bination of conditions, is more frequent than is gener- ally believed to be the case. At all events, it will be perfectly safe to suggest that the clinician make a spe- cially careful examination of the abdominal walls and the position of the various abdominal organs when the Indicanuria and Enteroptosis 243 urine report shows that indican is present. In a recent communication Dr. Boardman Reed, of Los Angeles, Cal., emphasizes the frequency of abdom inal prolapse in pulmonary tuberculosis. He believes that the treatment of this disease is not complete with- out the suitable support of the abdominal organs if nec- essary. This is an important point and one worthy of much more extended attention. It has been found that the absence of indican in the urine of the tuberculous is the exception rather than the rule. Whether other investigators will corroborate these statements matters little; the fact remains that these two clinical findings — indicanuria and enteroptosis— 1 have been repeatedly found together. As a matter of course, therefore, the obvious therapeutic indications have been acted upon in the treatment of these patients, with very favorable results. The raison d'etre of this combination is not difficult to explain. Indicanuria is considered by the majority of physiological chemists to be due usually to putre- factive changes in the intestinal contents. The pres- ence of the poisons generated under such circumstances must, of necessity, have an unfavorable effect on the intestinal walls, and especially on the glandular and muscular portions. In consequence the glands do not secrete • their normal fluids and the intestinal muscula- ture loses its tonicity, with the inevitable dilatation, constipation and other accompanying symptoms. This very combination is an important factor in the produc- tion of prolapsed viscera, and, associated with the gen- 244 Essays on Laboratory Diagnosis eral autointoxication which is the usual accompaniment, the abdominal walls become flaccid and permit of the gravitation of the abdominal contents. As a result the intestinal disturbances are rendered worse and in this way a vicious circle is established, which can rarely be remedied by the ordinary eliminative treatment. The removal of indican from the urine is, in most cases, a comparatively easy matter. Stimulation of the emunctories and a judiciously selected dietary in which the proteid content is reduced to the minimum will, in a reasonably short time, cause a diminution in the putre- faction going on in the bowel, and with it, of course, a disappearance of the indican. It will be found, how- ever, that the majority of these patients revert sooner or later to the old state of affairs, and the conditions here under discussion return and become as bad as ever. For this reason I am of the opinion that the usual therapeutic and dietetic measures are not all that might be desired. If one adds to the usual treatment outlined very briefly above the proper support of the abdomen by means of a suitable corset or binder, and emphasizes the importance of several dietetic maxims, such as da- liberate eating, simple food combinations and less meat or other foods high in proteids, it will be found that considerably better and more lasting effects will be ob- tained in the treatment of autointoxication, due to in- testinal putrefaction and its results. It would seem that the best support for women is the front-lacing cor set in which the waist is snug, but not tight. Men may Indicanuria and Enteroptosis 245 use a supporter made on the same principle, but not ex- tending above the waist. One manufacturer here in Chicago is making a specialty of scientifically fitting such cases for the profession. It must not be supposed that because indicanuria and enteroptosis have been so often found together that the removal of the one necessitates the disappear- ance of the other. Excessive intestinal putrefaction may be inhibited and indican promptly disappear from the urine, but the prolapsed abdominal organs remain where they are. On the other hand, a finely fitting ab- dominal support may be used for months and indican still be found in excess. The treatment of this combination of conditions is evidently a matter of judiciously com- bining the various essentials mentioned above. In closing I will make the following conclusions and suggestions : 1. When indican is found to excess in the urine, look for prolapsed abdominal viscera and the usual ac- companying results. 2. When enteroptosis is evidently present, look for indican in the urine. 3. In the treatment of intestinal autointoxication, in addition to the usual dietetic and eliminative treat- ment, support the abdomen. In so doing, the desired results will not only be more quickly achieved, but they will be more permanent. 4. The treatment of chronic intestinal putrefaction is not complete unless special efforts are put forth to strengthen the abdominal walls as well as the intestinal 246 Essays on Laboratory Diagnosis musculature by such physical measures as exercise, mas- sage, electricity (especially the sinusoidal current), hydrotherapy, etc. 5. The statements of certain investigators to the contrary notwithstanding, indicanuria is distinctly a pathologic condition and must always be considered as such, no matter how good the general health may ap- pear on superficial examination to be. [Editor's Note. — A carbon copy of the above paper was sent to Dr. Boardman Reed, with the request that he comlment thereon if he felt so inclined. His answer, received just as we go to press, contains the following interesting statements : "The points in your paper are well taken. One of them, however, I would probably put a little differently. I believe that when indicanuria is present in enteroptotic patients, as it very frequently is, the enteroptosis has usually been the primary cause of the indicanuria, by interfering with excretion through the bowel. Perhaps both may have had a common cause in the very prevalent overloading of the stomach. Still, as is intimated, a vicious circle is ultimately produced in either case, and matters go on from bad to worse. "It will interest you to know that in my experience I have seen a number of bad cases of asthma greatly re- lieved, and some of them radically cured, by strapping up an associated prolapsed stomach and right kidney. In these cases there was a coexisting indicanuria which, of course, had much to do with the causation of the asthma."] XXIV. THE VALUE OF THE URINALYSIS IN DERMATOLOGY. Reprinted from THE AMERICAN JOURNAL OF DERMATOLOGY, St. Louis, May, 1909. CHAPTER XXIV. THE VALUE OF URINALYSIS IN DER- MATOLOGY. It is well known that many dermatoses are caused directly or indirectly by disturbances of the relation be- tween the anabolic and eliminative functions of the body. Frequently certain normal poisonous products are not properly eliminated from the system, while, on the other hand, an excess of abnormal waste is manufac- tured in the body, causing more or less serious trouble. These effete substances, the most of which seem to be acid in reaction, are carried around in the blood-stream, causing many inconveniences to the patient, not least among which are skin affections. Probably no one condition is as prolific in its causa- tion of skin diseases as autointoxication. This disease, if I may so call it, is very common in this country for several reasons. First: The irregular, sedentary life of the majority and the general high pressure under which the most of us live. Second: The excessive amount of food, and in particular proteid, that is usually in- gested. Third : The rapidity with which food is usually eaten. All these factors are conducive to serious dis- turbances which have as their direct result a general toxemia, and indirectly a condition of lowered vital re- sistance which is often, associated with skin manifesta- tions of varying severity. Since the examination of the urine (and by that I 250 Essays on Laboratory Diagnosis mean the complete qualitative and quantitative examina- tion and not simply the mere testing for specific gravity,, sugar or albumin that is so often done) affords such a clear insight into the. actual conditions present in the body, this routine is of great value to the physician in his practice. It opens up new fields for therapeutic ac- tivity, which, without the findings of the urinary exam- ination, would either be unnoticed or not fully appre- ciated. Particularly is this true in the practice of der- matology, because of the very close connection between certain skin diseases and the metabolic activities of the body. It is surprising how many skin affections are asso- ciated with acid intoxication or acidemia. Acne, herpes, eczema, pruritus and many other conditions seem, from results obtained in their treatment, to be entirely due to this condition. This is at least true in some cases, for when the offending cause is removed and the poisonous substances present are properly neutralized and elimi- nated from the body, the offending skin lesions disappear without further attention, in the majority of cases. The examination of the urine is a measure which should be carried out as a routine in every case, not only in dermatology but also in general medicine. The urinary examination offers a number of definite find- ings associated with acidemia and autointoxication, the most important of which are the presence of indican and indol-acetic acid, both of which are products of pro- teid putrefaction in the body, together with an excessive degree of acidity. The Urinalysis in Dermatology 251 A factor of vital importance, which has as yet not received the attention that it merits, is the urinary acid- ity. Unfortunately, the medical profession still believes in the textbook statements that the test for acidity or al- kalinity with litmus paper is sufficient ; but this is not so. In every case the degree of acidity should be accurately estimated and the relation of the degree of acidity to the amount of urine passed in twenty-four hours care- fully ascertained. Dr. A. L. Benedict of Buffalo, N. Y., has shown that the relation between the acidity and total amount is important. This is termed an "acid-unit" and is ob- tained by multiplying the degree of acidity of a speci- men from a mixed 24-hour collection by the amount (in cubic centimeters) passed. The average normal number of acid-units is about 40,000 in 24 hours, corresponding to 1,000 c.c. of urine of 40° acidity or 1,300 of 30 CT . The quantitative estimation of these factors is un- doubtedly of considerable value, as they are very closely related with other abnormal urinary findings. The ex cessive acidity which is so common is due to certain acid substances manufactured during the process of the de- praved metabolic conditions practically always associ- ated with intestinal putrefaction. The most common dermatosis — acne vulgaris — is almost invariably associated with a greater or less de- gree of autointoxication, as probably the most frequent exciting cause is a disturbance of digestion with an accompanying constipation. In these cases an examina- tion of the normlal products of metabolism eliminated 252 Essays on Laboratory Diagnosis in the urine very often makes plain the way for suc- cessful treatment. Conditions previously assumed to be due to some basal neurotic difficulty, as, for example, herpes, will be found in the majority of cases to evidence in a marked degree the findings associated with autointoxi- cation, and particularly to show an excessive degree of acidity. One case of herpes zoster of very long stand- ing which comes to my mind showed the following urinary findings: Amount 1,250 ex., specific gravity 1,014, total solids 40.75 grams, acidity 78 degrees, acid- units 97,500, urea 1.1 per cent., indican much, with traces of indol-acetic acid. Thorough elimination by the use of calomel in broken doses, a saline each morning, with intestinal antiseptics and neutralisation of the acidemic condition, resulted in a remarkable amelioration of the condition. The con tinuation of the local remedy which had been previously prescribed for this lady, together with this modification of the systemic acidity, caused a serious condition of long standing to disappear within a month. This, of course, is only one case, but many other skin diseases have responded remarkably to the systemic treatment of those conditions evidenced by definite urinary findings. The laboratory examination of many hundreds of specimens of urine, passed in every case by individuals -whose condition was far from the normal, shows con- clusively that many unpleasant symptoms (very com- mon ones of which are skin eruptions and irritations) and even dangerous conditions are closely associated The Urinalysis in Dermatology 253 with and possibly directly caused by excessive urinary acidity and those disturbed metabolic relations causing this condition. In a series of 250 cases recently reported by me in the Medical Record the average acidity was 60 degrees, the lowest being ten degrees and the high est 274. The acid-unit index varied from 100,000 to 200,000 per day; the minimum in this series being 8,030 and the maximum 358,050. In 25 per cent of these cases casts and traces of albumin were found, and in 83 per cent indican was present to a greater or less ex- tent, usually in large amounts. Another fact of considerable importance was the findings regarding urea. In these 250 cases the amount of urea eliminated was reduced an average of 50 per cent of the percentage normally eliminated in 81 per cent of the whole series, showing definitely that the condition of high acidity is very frequently if not prac- tically always associated with a lowered urea output and a marked indicanuria. Of course, the most important part in this paper will be the therapeutic indications of these findings. In my estimation, every individual suffering from dermal affections, no matter how insignificant or how severe, should have a complete urine examination. The ortho- dox local and systemic treatment may be very satisfac- tory, but it should always be supplemented with thor- ough elimination, repeated frequently, and a neutraliza- tion of the hyper-acid state of the body, using the urin- ary acidity as the index. This can be easily accom- plished by the cautious use of alkalies, and it will be 254 Essays on Laboratory Diagnosis surprising how many cases in the routine work of the skin specialist will yield to treatment along these lines. From the foregoing it must not be supposed that alkalies are a panacea for all skin diseases, but when the urinary findings show an excessive degree of acidity and this is brought down to normal by the judicious use of alkaline remedies, guided always by the acid in- dex, success will often be attained. XXV. THE LIFE INSURANCE "URINE EXAMINA- TION"— A FARCE. Reprinted from AMERICAN MEDICINE, New York, October, 1909. CHAPTER XXV. THE LIFE INSURANCE "URINE EXAMINA- TION"— A FARCE. From the above heading many readers will undoubt- edly expect to see some decided statements, and their expectations will be gratified. It is admitted that the thought embodied in the title of this brief article is fairly strongly stated, but, at. the same time, it is to my mind absolutely true, and there are many medical jour- nals of repute which are not afraid to publish an ar- raignment, so to speak, of the present methods of urinalysis in general practice, and, in particular in the analysis made in the routine examination for life insur- ance. I believe that I am not overstating matters in the least when I say that the urine examination properly performed and as extensive as circumstances will per mit, is one of the most important single diagnostic pro- cedures that we have. By saying this, I do not imply that other methods of precision are not valuable, but none of them gives as many pointers, either diagnostic or therapeutic, as the one series of tests called the urin- alysis.- All reputable life insurance companies naturally de- mand a thorough examination of the prospective appli- cant for protection, in order that their medical directors and those under them can decide whether a case is worthy to receive a policy or not, so that their risks may be as sure as possible. I have had some slight ex- 258 Essays on Laboratory Diagnosis perience as an examiner for the Metropolitan Life In surance Company, and have seen a number of the ex- tended blanks of several other large companies which the medical examiners are expected to fill out in the rou- tine of the so-called "medical examination." Both the old-line and the fraternal companies require careful med- ical examinations. The urine examination is usually part of the procedure, and it is about this examination that I wish to express a few thoughts. Frequently the examiner is expected to receive a small specimen in his office; no special effort is made to have a part of a mixed twenty-four-hour collection, and some companies prefer a specimen passed right in the office, thus eliminating the possibility of substitution. The specific gravity is usually ascertained with the crude 35-cent urinometer so frequently found in the av- erage physician's office. The urine is liion boiled and perhaps Heller's test for albumin is carried out. Either the Fehling or Haines method is advocated for the de- tection of sugar. Some companies require more than this, but they are few and their requirements are not very much more extensive. Let us dissect such urine examinations and the pos- sible findings as mentioned above. Suppose the specific gravity is above the limit usually mentioned in the in- struction books to company physicians. Is it not entirely probable that the examination for specific gravity of an individual passage of urine passed during the summer months will show a specific gravity of from 1,025 to 1,030? Is it not possible for an individual to have par- The Life Insurance Urine Examination 259 taken quite freely of nitrogenous food, or to have made use of a little more than the usual amount of table salt,, and in this way increase the specific gravity of his speci- men? On the other hand, is a specific gravity of 1,008- 1,010 not of common occurrence when the individual has drunk freely of water, especially when specimens are taken at random? Again, the test for albumin is another source of trouble. A positive reaction does not occur in many cases which evidence renal disturbances, and often traces of albumin may be present when there is no serious disease. I am acquainted with several individuals, and have heard of many others, who have been refused life insurance for the simple reason that there was a trace of albumin in their urine. Is there not such a thing as alimentary albuminuria? Is it not possible for albu- min in the urine to be there temporarily, just the same as an excess of chlorides or a diminution in the phos- phates ? As a matter of fact, in my experience, which ■covers a number of hundreds of examinations, I have found that albumin, and even casts are comparatively frequently found associated with an excessive degree of urinary acidity — a condition which, when properly treated, may be speedily ameliorated with a resultant disappearance of both casts and albumin. It is not to be presumed from the statements above that the presence of albumin in the urine is a matter of minor importance to be neglected or overlooked. A persistent albuminuria is usually evidence of something abnormal, and if the associated functional abnormal!- 260 Essays on Laboratory Diagnosis ties are modified and the albumin still persists, there is probably an organic disturbance. In this case, of course, the insurance risk is bad. The test for sugar is usually crudely carried out by more or less unskilled hands, and very frequently in a big hurry. Fehling's solution is the most common rea- gent, and is by no means infallible. A number of sub- stances are known which reduce this and other copper test-solutions, and since this is a fact, would it not be well to be sure that the reducing substance present is positively sugar? For this reason the phenyl-hydrazine test is suggested, or, as a fair substitute, the fermentation test. And even if sugar — real, unadulterated glucose — is present in small quantity, the one examination is not enough, for it is entirely possible to have a condition of alimentary glycosuria. As I have written before in other articles, a urine examination comprising only the tests mentioned above — specific gravity, albumin and sugar — is a very crude procedure. It might well be much more extensive and give the examiner information of much more extended value. For this reason I would suggest as a matter for thought the advisability of having the urine examination which accompanies applications for insurance for $1,000- or more, made by an expert who knows how to do the work properly, said examination to include in addition to the usual physical measures, the chemical examina- tion for albumin, sugar, bile, blood and indican and a quantitative examination for urea, acidity, ammonia and perhaps chlorides and phosphates. In addition to this, of The Life Insurance Urine Examination 261 course, a careful microscopical examination of the cen- trifuged sediment should also be made.. From such an examination it would be evident wheth- er the individual was in a normal state of metabolic equilibrium ; whether there was a disturbance of the kid- neys or any other part of the urinary tract; whether there was an excessive degree of intestinal putrefaction, or other gastro-intestinal disturbances. In short, it would be a measure of real diagnostic value. What is worth doing at all is worth doing well, and I contend, therefore, that if the examination of the urine has been found necessary and advisable in life insurance practice, that it might as well be done thoroughly. This naturally also applies to the urinalyses accompanying all physical examinations, whether for therapeutic sugges- tions or what-not. Conclusions: 1. The examination of the urine, and especially that made for the benefit of life insurance companies, is altogether too crude and not nearly ex- tensive enough. 2. Because of this, individuals are be- ing refused life insurance who would make excellent risks, and, on the other hand, others are "passed" who are by no means what might be called healthy, and, in fact, are in a serious condition. 3. The examination should be made by such as are skilled in this work, and should be paid for accordingly. Three dollars is not an unreasonable figure. 4. There is room for considerable improvement in the work at present done along those lines, and it is to be hoped that with frequent and per- sistent stimulation progress may be eventually secured. XXVI. METABOLISM AND MOUTH-DISEASE. (A paper read before the Section on Stomatology, American Medical Association, St. Louis, June, 1910.) Reprinted from THE JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Chicago, October 1st, 1910. Copyright, 1910, by American Medical Association. Reprinted by permission. CHAPTER XXVI. METABOLISM AND MOUTH-DISEASE Since there is a very close relationship between the functions of the various organs of. the body, it is not unreasonable to suppose that disorganization in one part will be accompanied or followed by disturbances else- where. From a study of conditions as they are today in both medicine and dentistry, however, it would seem that this important fact is not as fully appreciated as might be expected. It is generally believed that certain more or less in- tractable diseases of the mouth or its contents are, to a greater or less degree, either accompanied by or asso- ciated with changes in the normal metabolic functions of the body. In spite of this, comparatively few physi- cians are stimulated to look carefully into the mouth when evident errors of the metabolism are known to be present ; nor do our dental confreres investigate the meta- bolism of those of their patients who are suffering from the all-too-common and intractable mouth diseases. This is not as it should be, for any local manifestation of disturbed function should serve as a reminder that a thorough investigation is not only necessary, but imper ative. This is just as true of mouth diseases as of skTn eruptions, joint difficulties or gastro-enteric disorders. All too often Nature's glaring sign-posts are ignored. Without a doubt there is a very close relationship" 266 Essays on Laboratory Diagnosis between the condition of the buccal mucosa, the gums and teeth, as well as the tongue, and the blood which nourishes them. From time immemorial the condition of the tongue in disease has been used as an important diagnostic sign, and the study of this is given a promi- nent place in the text-books and current medical litera- ture. For this reason I give it merely passing mention here. It might be well here to quote a few lines from a valuable editorial entitled "Gingivitis in Diabetes" print- ed in a recent issue of The Journal : "The importance of mouth symptoms in the acute infections, such as scar- let fever, diphtheria and measles, is recognized. It is less generally known, however, that in many constitu- tional conditions the mouth secretions and the mucous membranes covering the gums, cheeks, tongue, etc., fur- nish early and positive data for diagnosis. "It becomes a matter of extreme importance, there- fore, that the general practitioner shall examine the mouths of all patients, taking careful note of the mucous membrane of the cheeks, beneath tne tongue, on tne tongue itself, the roof of the mouth, and especially the gums." The work of a number of broad-minded investigators, among whom the esteemed secretary of this Section, Dr. Eugene S. Talbot, sta«ds pre-eminent, has called the attention of both the medical and dental professions to the relationship between pyorrhea alveolaris and certain blood dyscrasias. This subject is of paramount import- ance and one to which much more attention should be Metabolism and Mouth-Disease 267 paid. Here we have a vital factor in the solution of a multitude of difficulties, not merely pyorrhea alone, nor, for that matter, mouth diseases per se, but of a long list of common and uncommon conditions which embrace almost all the diseases known to medicine. It is a fact that as a profession we have not yet fully grasped the meaning of the Biblical statement, "The blood is the life." I do not mean by this that we do not appreciate the fact that life is dependent on the blood and its healthy condition, but the fact that in the majority of cases disease is due to toxic wastes which are present in the blood-stream and which unquestionably markedly lower its disease-resisting powers. These poisons are not all of them sufficiently weil known to have been isolated and named, but their fre- quent presence and easily demonstrable untoward effects are apparent to all that take the trouble to look for them. Principal among these disease-producing toxins are certain acid substances which have been demonstrated to be closely related to indican and other products of intestinal putrefaction. Just what these substances are remains to be proved, but that they are acid in reaction and that their baneful influence is evident in the mouth as well as throughout the whole system is very quickly and easily proved. Our methods of analyzing the blood and estimating its alkalinity are altogether too complicated for general use. In their place the examination of the urine has been found to be at once convenient, quick and easy; and the results obtained from such examination will be 268 Essays on Laboratory Diagnosis found at times to be even startling. Probably the one factor obtained by the careful analysis of the urine which in most cases overtops its fellows is the acid-index, and, strange to say, hardly more than a mention of it and the method of its estimation is to be found even in the most recent text-books. Let us for a moment consider the question of the urine analysis and the relations of some of the findings. The urine is usually acid in reaction and the average normal acidity ranges from 30 to 40 degrees (each de- gree represents the amount of decinormal soda solution required exactly to neutralize 100 c.c. of urine). This acidity, we are told, is due to certain acid salts, principal among which is the acid phosphate of soda. We learn from the text-books that the urinary acidity is very dif- ficult to accurately estimate because of the trouble in securing an indicator which will be more responsive to all the various acid salts, and probably for this reason the study of this most important finding has been largely passed over. Phenolphthalein is the most satisfactory indicator and is used by the majority of investigators. The test is simplicity itself and is fully as accurate as many of the well-known and widely used tests, as, for example, the albumin tests of Esbach or Purdy, or the Doremus urea test. The acidity of the urine should always be de- termined from a portion of a complete twenty-four-hour specimen, and care should be taken to prevent, as far as possible, alkaline decomposition of the urine. Either a burette or my acidimeter may be used. The latter is Metabolism and Mouth-Disease 269 far more convenient for the physician or dentist in his office, while the former' is probably better in routine laboratory work where large numbers of specimens i are being handled. In a paper published last June I called attention to the frequency with which excessively acid urine accom- panied indicanuria and a marked diminution in the amount of urinary solids passed. A series of 250 analy- ses was mentioned in this paper. These findings, aug- mented by much further work along this line both by myself and several interested friends, was reported in a paper read at the annual meeting of the Illinois State Medical Society held last month. From my findings it would seem, to me at least, that we have conclusive evidence that in the study of the urinary acidity we have something of more than ordi- nary importance. The relation of this syndrome of find- ings — acidemia evidenced by a hyperacid urine, intes- tinal toxemia by indicanuria, and decreased metabolic activity by the frequent low urea index and general re- duction in the total solids — to mouth-disease, is quickly found. It is safe to say that a majority of patients suffering from pyorrhea are acidemics, and the most conclusive feature of this work is that therapeutic meas- ures calculated to reduce the acidemia and eliminate the toxemia have a decidedly beneficial effect on the pyor- rhea. Many patients have been examined by me personally. Dr. Talbot has made hundreds of examinations and sev- eral others have by their work proved absolutely that 270 Essays on Laboratory Diagnosis there is decided and close connection between disturbed metabolism and mouth-disease. I might go further and discuss the relations of th* metabolism as evidenced by the urinary findings to dis- eases of the buccal mucosa, the pharynx and the tonsils, but this is a subject far too broad to be touched on as briefly as would be necessary here. It is hoped that a widespread study of the relations between the disturbances of metabolism and mouth af- fections will shortly be inaugurated among the rank and file of the professions, and that the dentists as well as the doctors will come to see the important influence that the hyperacid state plays in disease causation in general and in mouth disorders in particular. XXVII. THE IMPORTANCE OF THE CLINICAL LABORATORY IN SURGERY. Reprinted from THE AMERICAN JOURNAL OF SURGERY, New York, October, 19 jo. CHAPTER XXVII. THE IMPORTANCE OF THE CLINICAL LAB- ORATORY IN SURGERY. Every surgeon realizes that his work does not sim- ply consist in performing operations. There is a great deal more to an operation than the removal of diseased tissues, and if the surgeon's mind is not too firmly fixed on the operative condition, but is trained to include every helpful or hindering factor, ultimate success — not merely surgical success — will be the result of his work. It is generally considered that the facilities of a clin- ical laboratory offer the surgeon much assistance in gaining a general insight into his patient and his inner workings. Laboratory investigations have come to be imperative procedures prior to an operation, and, again, in many cases the laboratory is made an efficient guide to the post-operative treatment. When a physician situated in a large city has a case requiring surgical attention, the hospital is naturally one of his first thoughts. One rarely finds a surgeon oper- ating upon his patient at home unless the case happens to be one of great emergency, or there is marked antip- athy to the hospital. Indeed, today it is customary for both laity and profession to immediately associate the thought "operation" with "hospital." This is, of course, right and proper, and the advantages provided by an up- to-date hospital are essential to the convenient prepara- tion and after-care of the patient. But the advantages 274 Essays on Laboratory Diagnosis of the hospital do not consist simply in a splendidly equipped operation room and the various paraphernalia used in or near it, but also — and this is by no means the least important — in the clinical laboratory, in which the various essential investigative measures can be conven- iently and thoroughly carried out. For this reason the laboratory and its work have be- come a matter of comparatively little concern to the city physician or surgeon, since his telephoned instructions are to "Make a blood examination for X.," "Have Y's urine carefully examined," or whatever the exigencies of the case demand. In many cases there is a standing order for a definite laboratory routine which is carried out in every case. This is as it should be ; but, unfortunately, frequently there is not quite as much interest evinced in laboratory methods among the surgically inclined physicians who happen to be situated in those districts where laboratory facilities are not so convenient as in the city and the work is not so easily done as by simply ordering it over the telephone. While the fact cannot for one moment be contended that the need is just as great whether in the city or in the country, this is not often appreciated, and all too frequently the perfunctory test of a single specimen of urine for albumin and sugar constitutes the sum total of the "laboratory work" done by many provin- cial surgeons. For this reason it would seem that more attention must be given by many physicians to the im- portance and advantages of laboratory help in surgery. Of course, it is easily understood that many surgical The Clinical Laboratory in Surgery 275 conditions are diagnosed by laboratory procedures and in many more the tentative diagnosis is definitely estab- lished after, say, a blood examination or some other lab- oratory investigation. Still, to my mind the laboratory offers the surgeon its very best services in laying bare the other important conditions present in his patient which, if overlooked, might prove a serious menace, or, at least, a hindrance to the successful outcome of either the operation or the anesthesia. The urine examination is one of the most import- ant preoperative diagnostic procedures. The urine of every individual upon whom an operation is expected to be performed should always be carefully examined prior to the operation at least once. Two or three times would be much better, since sometimes certain urinary findings may be unusually marked or entirely absent in one single specimen. The examination for albumin alone is not sufficient, for its presence is not necessarily evi- dence of structural kidney disease, nor, for that matter, need the finding of hyaline casts be considered as se- rious. These tests, of course, are not valuable unless the functional capacity of the kidneys and liver, as well as the metabolism in general, are also known. The phy- sician who neglects to study these points is overlooking possibilities which may be of prime importance to the success of his work. Naturally, if organic renal disease is present the an- esthetist hesitates to administer a general, anesthetic. Is it not just as dangerous to contend with other conditions that are not evidenced by the crude and practically worth- 276 Essays on Laboratory Diagnosis less tests that are commonly used? The importance of the relation between the normal elements of the urine, as well as the presence of abnormal elements, should receive just as careful attention, for from these figures a far better idea of the metabolism may be obtained. It is well known that certain insidious disturbances of metabolism may be present in an individual without any decided symptoms to warn him of this fact. It is quite reasonable to suppose that a tolerance to these con- ditions may be interrupted or entirely lost when he suf- fers from a severe traumatism or the heavy burden of a general anesthetic. For this reason it is believed that the urine should always be quantitatively tested for acid- ity, total solids, urea and indican, in addition to the other tests for abnormal elements such as albumin, glu- cose and the acetone bodies. It might be well also to include in the routine a test for occult blood and bile, for obvious reasons. Attention should be given to the acidity of the urine, for it has been found to be a very reliable guide to the general vital resistance. It is well known by physiolo- gists that upon the proper maintenance of the normal alkalinity of the blood depends the proper carrying out of its normal functions ; in other words, if the alkalinity is reduced, the normal interchange of gases cannot take place, phagocytosis is disturbed, and the resistance of each microscopic cell structure is materially diminished. This would seem to be an important factor in the pre- operative investigation of a patient, since many surgical operations, as gynecological operations, are done after The Clittical Laboratory in Surgery 277 considerable premeditation, and not on the spar of the moment. In these cases, at least, it is reasonable to presume that both patient and physician are anxious to have every circumstance as propitious as possible, and in my opinion a patient coming for an operation with a urine showing the total acidity to be increased two or three hundred per cent is not in the best condition either to stand the anesthetic or to recuperate after an opera- tion. The general conditions that are associated with a marked diminution in the amount of urinary solids, and especially urea, are of paramount importance. It must be remembered that not only is there frequently a rela- tion between low solids and renal disease, but very often it will be found that the liver and thyroid are not func- tionating as they should. When this is the case, and the solids are less than half the normal that should be passed in twenty-four hours, the circumstances are not nearly as favorable to a successful outcome of an operation as though they were practically normal. The condition of the bowel must needs be a prolific cause of diminished resistance and undoubtedly advances have been recently made in the study and appreciation of these conditions and the findings associated with them. Autointoxication must be considered as an absolute con- traindication to all save emergency operations. The presence of indican jn the urine should always receive attention, "^jjhgugh it is granted that indican itself may be an entirely innocuous substance. It is reasonable, however, t^ suppose .that the conditions which excite 278 Essays on Laboratory Diagnosis its manufacture are, to say the least, ; n Saturated (40%) sodium hydrate solution, 1 lb. (urea) ,. . .35 Spiegler's solution, 8 oz. (albumin) 50 Nitric acid C. P., 4 oz. (albumin) 20 Tsuchiya's reagent, 8 oz. (albumin) 85 Hydrochloric acid C. P., 1 lb. (indican).. .35 Acetic acid glacial, 4 oz 25 Meyer's reagent, 4 oz. (blood) 75 Haines' solution, 8 oz. (sugar) 40 Decinormal soda solution, 1,000 cc. (acid- ity, etc.) 1.00 Lugol's solution, 4 oz. (starch) 20 Barium mixture, 8 oz. (sulphates) 30 Magnesium mixture, 8 oz. (phosphates) . . .25 Test papers — red and blue litmus and congo red 30 Ferric chloride 10%, 1 oz. (diacetic acid). .15 Sodium n ( itroprussied, % oz -, (acetone) ... .35 Ammonia water, 8 oz. (blood, acetone, etc.) 25 Phosphomolybdic acid solution, 1 oz., (uric acid) 35 $8.20 This makes a total of about $20.00. The prices will The Twenty-Five -Dollar Laboratory 291 vary 'slightly, although I am confident that the above figures might even be bettered if the purchasing is done at a supply house instead of at the corner drug store. Books must not be forgotten. The best two books, in my estimation, are Faught's "Essentials of Labora- tory Diagnosis" at $2.00 (F. A. Davis Company, Phila- delphia) and Saxe's "Examination of the Urine" at $1.75 (W. B. Saunders Company, Philadelphia). So. you see, one can get a whole lot into a $25.00 office laboratory, and if- any reader of The World wants to ask any questions and has a two-cent stamp to enclose I shall be most happy to offer them my best assistance and co-operation. 921 Schiller Bldg., Chicago.