New Medications. PART I. By Prof. Dujardin-Be&umetz. REASONS FOR PRESCRIBING Fairchild’s Pepsin. It is the most active, gives the greatest value for the price asked. One grain will digest more albumen than will a grain of any other pepsin made. We do not care by whose test, what the proportions of albumen, water, and acid, only let the conditions be the same for all. It is positively guaranteed to be permanent. It will not get soft or sticky, or deteriorate in value, because it is not a peptone. It is free from all the well-known characteristics of peptone. It is not made by a patented or pirated process. If you prescribe pepsin in scale or powder, and it becomes sticky, you may be sure that it is not Fairchild’s. Investigate the matter, place the blame where it belongs. There are pepsins “made to sell” under the title of scales—products which are inferior and dissimilar to Fairchild’s pepsin in scales. They are peptones made by a patented process, and sold under cover of a title first and properly used only by Fairchilds to describe their original true pepsin in the form of scales. The druggist is told, “They are just as good as Fairchild’s. If Fairchild’s is not specified, put in mine.” But claims and pretensions, however colossal, cannot make peptones permanent. There is no soluble or peptone pepsin equal in activity to Fairchild’s, none which will keep in all weathers and all conditions as Fairchild’s will. FAIRCHILD BROS. & FOSTER, !LT e-w "2" oris. New Medications, PROFESSOR DUJARDIN-BEAU METZ, Member of the Academy of Medicine and of the Council of Hygiene and Salubrity of the Seine; Physician to the Cochin Hospital; Editor-in-Chief of the Bulletin Giniral de Thira- • peutique, Paris, France. TRANSLATED BY E. P. HURD, M. D., Member of the Massachusetts Medical Society; Member of the Climato- logical Society; Member of the Society de Medicine Practigue, (Paris. France). One of the Physicians to the A nna Jacques Hospital, Newburyport, Mass. SECOUD EZDITIOnsr. Revised and Corrected, with Additions and Illustrations. 1890. GEORGE S. DAVIS, DETROIT, MICH. Copyrighted by GEORGE S. DAVIS. 1890. TABLE OF CONTENTS. CHAPTER. PAGE. I. The Great Discoveries in Therapeutics of the past Fifty Years i II. On New Cardiac Medicaments iS III. New Methods of Treating Stomach Diseases 43 Appendix to Chapter III 61 IV. New Gastro-Intestinal Medications 74 V. Antiseptic Intestinal Medication 90 VI. Antiseptic Medication in General 104 VII. New Pulmonary Medications. .* 120 TRANSLATOR’S PREFACE. Dujardin-Beaumetz is now so well known in this country that any production of his will be welcomed by progressive American physicians. Editor of a leading therapeutic journal (the Bulletin Gen- eral de Thtlrapeutique), physician-in- chief to the great Hospital Cochin, where multitudes of patients are constantly under his general supervision,and where a spacious amphitheatre has been erected for his use in clinical teaching, also a fine labora- tory for clinical and physiological investigation, the author of this work by his pen and by his oral instruction is the centre of a wide influence, inspiring a host of ardent workers to alacrity, diligence and thoroughness in promoting the cause of scientific and practical medicine. Of his numerous publications, the following have been translated by myself: x. Clinical Therapeutics. G. S. Davis, Detroit. 1885. This book is the third volume of the Lecons de Clinique ThJra- peutique. 2. Diseases of the Stomach and Intestines. Wm. Wood & Co., New York 1886. (This volume belongs to the Medi- cal Library Series for 1886.) 3. Diseases of the Heart. Two volumes. G. S. Davis, Detroit. 1887. 4. Diseases of the Liver. G. S. Davis, Detroit. 1888. 5. Diseases of the Kidney. G. S. Davis, Detroit. 1888. Besides the above, which have appeared in book form, those who have files of the Therapeutic Gazette will find running through the numbers of the past four years, lectures whose en- semble constitutes the volumes which have been recently pub- lished in France under the titles: “ Le Hygiene Alimentaire',” “ L’ Hygiene Prophylactique,” “ L’ Hygiene Therapeutique.” The term, New Medications, which has been chosen as the title of this book,is suggestive of the necessary implication that there are old medications, some very old, and which have been in vogue ever since the human race first emerged from a state of utter barbarism and learned to treat the sick by rational methods, rather than to leave them to the mischievous meddling of the wizard, the sorcerer, or the savage medicine man. It cannot be asserted that the fathers of medicine were fools, or that the old medications which were the result of sound experience and observation, and have in past years been the basis of rational practice, are to be superseded by any new methods, except so far as the new better fulfil the indications, are more completely adapted to respond to enlightened views as to pathogeny, or furnish a more complete equipment to the physician. That some of the modern methods do meet these conditions and thus assert their right to pre-eminence, no care- ful reader can deny. The pathology of past ages furnished to the practitioner of medicine the same momentous problems for solution, and the same urgent indications; on the one hand, owing to the tardy progress of science, the data were lacking for a complete knowledge of the morbid conditions, and chem- istry and pharmacology on the other hand, had not yet given to the profession their powerful auxiliary resources. Hence there was room for the therapeutic advances which the nine- teenth century has realized. To illustrate my meaning: Bromide of potassium is a com- paratively new medicine, and no one will dispute that a great advance has been made in the treatment of the convulsive neuroses, and especially epilepsy, since this remedy was introduced into therapeutics, fulfilling, as it does, certain indications better than any of the old remedies. But this is X XI not all; this therapeutic gain is concomitant with a much more precise knowledge of these convulsive disorders than our predecessors possessed, as will be seen by comparing with our present treatises any standard medical work published a hun- dred years ago. But it is unquestionably true that some of the “old medi- cations ” were bad, and the enlightened physician of to-day has discarded them for modes of treatment more rational and scientific. Among these bud medications we may class blood- letting (which has almost passed into oblivion), and the anti- phlogistic use of calomel. Many of the medicaments on which physicians most rely are “old as the hills,” and will probably hold their place in the Materia Medica as long as sickness continues on this planet. As a pure analgesic it is probable that opium will never be surpassed or superseded. Iodide of potassium and mercury will probably remain the best specifics with which to combat the accidents of syphilis. Quinine (which is simply a handy form of an old remedy, cinchona bark) will still be the anti- malarial specific par excellence. Rhubarb, ipecac, senna, squills, and even castor oil, will still continue to meet certain indica- tions, and will not be crowded out of the Pharmacopoeia. But there will be a gradual weeding of the Materia Medica; many really useless medicines will be dropped, and less medicine will be given in the future; alimentation, hydrotherapy, etc., are to have a predominance—in fact the hygienic treatment of disease is destined to come to the front. Of the “new medications,” some are of prime utility. Sparteine and convallaria may be abandoned, but cocaine and acetanilid are permanent acquisitions to therapeutics. We may doubt the remedial value of grindelia robusta, but medical anti- sepsis has come to stay. Stomach washing (lavage) so ex- actly meets, therapeutically, certain pathological conditions that it must continue to hold a place in the treatment of stom- XII achal diseases. Certain of the new antipyretics mentioned in these pages will doubtless prove to be of great utility in the future. But progress in medicine is destined to be largely in the direction of what our author calls etiological therapeutics, i. e., in more definite and thorough knowledge of the causes of dis- ease, and the means requisite for their avoidance and elimina- tion. The “coming man” will assiduously labor to avert the predisposing and exciting causes, and here the earnest co- operation of the hygienist and microbiologist will often render unnecessary the interference of the pharmacist. In this work I have followed the author’s second revised edition. The chapter on Lavage and Gavage of the Stomach is reprinted from the volume on Diseases of the Stomach and Intestines, which appeared in 1886. It remains to add that this book comprises the Cochin Hospital lectures for the years 1884-85. Translator. Nkwburyport, Mass. PREFACE TO THE SECOND EDITION. Four years have elapsed since the first edition appeared. The work has been carefully revised and numerous additions made, so that the principal recent acquisitions of therapeutics might be included. The appendices to the chapters in the first edition, with the exception of the appendix to Chapter III, have been omitted from this edition, and what has been added to the text has been taken from rece it publications of the author. E. P. HURD, M. D. Nkwburyport, Mass., October ist, 1890. NEW MEDICATIONS. CHAPTER I. THE GREAT DISCOVERIES IN THERAPEUTICS OF THE PAST FIFTY YEARS. Gentlemen: I intend to continue in this hospital the instruction in therapeutics to which my medical life is devoted. Begun in the Hospital St. Antoine, this clinical teaching has already given to the world the volumes on “Clinical Therapeutics,” and I desire to add to and otherwise complete a work which has not I hope, been altogether without useful results. The commencement of my course of therapeutic instruction at St. Antoine was attended with trying diffiulties by reason of the material conditions in which I was placed. To-day my task is rendered easy and pleasant by the generosity and liberality of the Directors in placing at my disposal all the con- veniences necessary to facilitate and illustrate my course. Therefore I take this occasion publicly to thank the general manager and his secretary, M. Brelet, as well as the architect of this hospital, M. i l 2 Gallois, for the rapidity and dexterity which they have displayed in the execution of the different works which have transformed these ancient military barracks into a model modern hospital. For, by a happy concur- rence of circumstances, we find here, united under one roof, the amphitheatre, the laboratory, and the patients, so that we are enabled to carry on the work of teach- ing along with our experimental researches and clini- cal studies. In the present course we shall not leave the do- main of practice, and it is always the application to the sick person which is ultimately to decide whether the medicament supposed to be indicated is of any value. The laboratory will be of use to us almost exclusively in enabling us to ascertain the physiologi- cal, and especially the toxic, effects of the medicine under consideration, for I have little faith in experi- mental therapeutics. Being unable to produce in animals the greater part of the diseases which affect the human species, it is impossible for us to study in them the therapeutic action of the principal medicinal substances. Ordinarily we observe in subjects under experimentation not the therapeutic action but the toxic effects of the medicament, and it is not experi- mental therapeutics which we realize, but experi- mental toxicology. Are we then to abandon such researches? By no means, gentlemen, for a real interest attends them; they show us the more or less toxic influence of the 3 substance which we are testing, they guide us respect- ing the doses to employ, they often enable us, lastly, to give a physiological explanation of the effects ob- served. Hence you will see every day what great advantages you can derive from experimental re- searches of this kind. These tasks of the laboratory will also include the means most fitted for isolating the active princi- ples of medicinal substances. Finally, it is by the help of these laboratory experiments that we can ex- amine attentively the modes of elimination of medi- cines, and thus complete the study of what has been described under the name of pharmacodynamic action of medicinal preparations. Therefore, I would say to all those who prize the study of the treatment of diseases, to all those who are attracted by these researches of experimental phy- siology and therapeutics, to all who wish to glean in this immense field of materia medica, to all who desire to increase the number of our really useful therapeutic agents: Come to us; the doors of our wards are open to you; the laboratory, with all the means of investi- gation of modern science, is at your disposal; and you will find in me, in Dr. Bardet, chief of the laboratory, in my internes, Legendre and Sapelier, a readiness to give you the advice and the help which you require. But in order to be good therapeutists, you must be good clinicians. Hence our teaching will not be exclusive, and to the lessons in Clinical Therapeutics 4 which I shall have the honor to give you, will be joined lectures in Semeiology which Drs. Legendre and Sapelier will deliver every Friday, and the Lec- tures in Medical Physics and Chemistry by my labor- atory chief, Dr. Bardet; and I trust that you will derive profit from this multiple and complex course of instruction. I shall devote this first lecture to the great thera- peutic discoveries of the past fifty years. You must be tired of hearing it said that medicine has made no progress, that the treatment of diseases is just where the fathers of medicine left it. Others are free to admit that certain departments of the healing art have made advances, and point with complacency to recent valuable gains in surgery, obstetrics, and path- ological anatomy, but as for therapeutics, it has not kept up with the progress made in other divisions of scientific medicine. You will hear these statements made not only by persons outside of the medical pro- fession, but even by physicians in good standing; made, too, with such magisterial authority as to bring upon therapeutics undeserved opprobrium and con- tempt, and that branch of our science which ought to be the supreme end of medicine becomes a subject of little interest and is assigned to a secondary place. Against this scorn and contempt I utter my pro- test to-day in showing you that therapeutics has made progress, and it is enough for me in this connection to sum up the great gains which it has achieved in the 5 last fifty years, to convince you that therapeutics has not been as far in arrear as has been supposed. “ To relieve pain is a divine work,” says Hippo- crates, and you will not be surprised to learn that it has been in the warfare with physical suffering that therapeutics has put forth its greatest efforts—efforts which have been attended with signal success, for the physician is now enabled to triumph over pain in its complete suppression. In this connection, then, I ought to speak of three grand modern discoveries; anaesthesia, the application of chloral, and the use of hypodermic injections. AN/ESTHESIA. The first in importance of all these discoveries is that of anaesthesia. I know of none more admir- able or more useful, as by the sole fact of this dis- covery therapeutics has, in my judgment, surpassed all the other medical sciences. What would become of surgery if anaesthesia did not exist? How could we perform those remarkable operations on the ab- domen without the chloroform sleep? Hence Figuier was right in placing induced anaesthesia among the wonders of science, and in the same rank with the modern uses of electricity, steam power, etc. It was on the ist of September, 1846, that there took place in Boston, between Dr. Jackson and Wm. Morton, a dentist, an interview which was destined to 6 decide the fate of anaesthesia. The latter had been seeking to obtain of Jackson some means which would enable him to extract without pain a tooth from a nervous patient. For four years Jackson had been experimenting with ether, and had noted its anaes- thetic effect. He had been led to these investigations by the researches, early in this century, of Sir Humph- rey Davy on protoxide of nitrogen, and believing the occasion favorable, he proposed to Morton to admin- ister to his patient inhalations of ether. Morton was absolutely ignorant of what ether was, and Jackson provided him with a bottle of it. That very evening, in his own house, Morton inhaled some of the ether, and noticed that for seven minutes he completely lost sensibility of the skin. The next day he boldly attempted that famous first experiment with a patient whose name science has preserved—Eben Frost, Esq. He caused him to in- hale some ether, and during the anaesthesia which ensued, he extracted a tooth without pain. One month afterwards, October 14, 1846, Dr. Warren, of Boston, at the Massachusetts General Hospital, performed ablation of a voluminous tumor of the neck on a patient anaesthetized by Morton; the patient experienced no pain. Surgical anaesthesia was discovered. But Morton, forgetful of his obligations to Jackson, did not invite him to be present at this test operation. Two months after, December 22, 1849, Jobert de 7 Lamballe made the first application of etherization in France, at the Hospital St. Louis. The year following, and only a few months after (in February, 1847), Sedillot proposed to substitute hydrochloric ether for sulphuric. A month later, viz., March 8th, Flourens, in a communication to the Academy of Sciences, studied comparatively the an- aesthesia produced by sulphuric ether and that de- termined by hydrochloric ether, and proposed to employ a body which Soubeiran had discovered in 1830, and which resembled in many respects hydro- chloric ether; this was chloroform. In the month of November of the same year, Simpson, of Edinburgh, applied the anaesthetic effects of chloroform to the human subject, and thereafter this new anaesthetic became the rival of ether in the production of surgical anaesthesia. [Though chloroform is more speedy in its action, and produces more complete relaxation of the mus- cular system than ether, and though the after-effects are unquestionably somewhat pleasanter, yet ether is everywhere recognized as the safer anaesthetic, and on account of the many sudden deaths which have followed the administration of chloroform, the use of this anaesthetic in some parts of the world is (at least by popular and medical sentiment) condemned.] It is a curious fact, moreover, that while the whole world was celebrating the benefits of surgical anaes- thesia, he who was the first to think of applying 8 Davy’s discovery respecting laughing gas to surgical practice—I refer to Horace Wells—committed sui- cide, and by a strange freak of fate, he employed to accomplish his purpose etherization, which his trium- phant opponents had just introduced into medical practice. In this discovery empiricism had a place which was more apparent than real, and when we follow step by step the connection of events, we see that it was by a strictly logical process that the discovery of an- aesthesia was brought about. Davy, guided by his re- searches on the action of gaseous substances on the economy, employs first nitrous oxide; Horace Wells aims to apply this gas to surgery, and fails in his first experiment; Jackson suggests vapor of ether and Morton carries out the suggestion and obtains anaes- thesia thereby. Sedillot endeavors to substitute hydrochloric ether for sulphuric, and Flourens pro- poses chloroform which has so many affinities with hydrochloric ether. Finally Simpson establishes the bases of chloroformization. Hence, then, gentlemen, it was by a comparative study of the substances belonging to the same chemi- cal series that this grand discovery was made. But this comparative study did not stop with chloroform, and the other members of the group of ethyls and methyls were next taken up, and a great number of substances have been found, which, without displacing chloroform which still stands at the head of anses- 9 thetics, none the less have rendered important services in the department of surgical anaesthesia. It was this same comparative study which led Liebreich to the knowledge of that powerful hypnotic, chloral hydrate. Liebreich, in 1869, wishing to examine (as he himself says) the effects of certain substances which undergo decomposition in the organism, studied com- paratively trichloracetic acid, its salts and chloral, aud showed the hypnotic properties of this latter body, which Liebig many years before (in 1831) had obtained by directing a current of dry chlorine upon absolute alcohol, and which Dumas studied anew in 1834. You all know, gentlemen, the immense advantage which we daily derive from chloral, the annual con- sumption of which amounts to thousands of kilo- grammes. It was the same comparative study which led Cer- vello to counsel the usage of paraldehyd, for when you examine the atomic formula of chloral you see that it may be regarded as an aldehyd, the trichlor- ated aldehyd; hence the thought suggested itself of employing this paraldehyd, which is simply consti- tuted by the union of three molecules ot aldehyd. One of my pupils, Dr. Coudray, has lately embodied in his thesis the results which he has observed in our hospital service from the employ of this new hypnotic.* CHLORAL. *Coudray, On Paraldehyde, These de Paris, 1884. 10 But the discovery of surgical anaesthesia, and the introduction of chloral and its derivatives into medi- cal therapeutics, were not yet sufficient to allay all pains, and in particular neuralgic pains. The finding of a method which has, so to speak, revolutionized medical practice in henceforth furnishing a positive and rapid means for the introduction and absorption of medicaments, ought to complete these first discov- eries: I allude to the practice of hypodermic injec- tions. HYPODERMIC INJECTIONS. It is to a Frenchman that we are indebted for the first idea, or at least the first practical tentatives of the hypodermic method. On the 27th of December, 1838, Dr. Lafargue, of St. Emilion, presented to the Academy of Medicine a memoir having for its title: “ On the Therapeutic Effects of Certain Medicaments introduced Under the Skin.” Nine years after, in 1847, Lafargue returned to this method, and noted with regret that despite the advantages which he had derived from it, the practice of inoculation of medica- ments, as he called it, had been received with the most complete indifference, and that nobody had put it into use.* In order to practice these medicinal inoculations, Lafargue proposed the following means: * Lafargue, On the Therapeutic Advantages of the Inoc- ulation of Morphine and Other Energetic Medicaments j(Bull. Gen. de Ther., 1847, xxxvii). 11 A long needle is taken containing a deep grove running its whole length, which is filled with muriate of morphia reduced to a paste; thus armed, this needle is plunged into the tissues and allowed to re- main there till the morphine is dissolved. It is sufficient to read this passage of Lafargue to see how little was needed to transform the method of inoculation of medicaments into that of hypoder- mic injections, and this is what was done thirty years ago by a Scotch physician by the name of Wood. Guided by the labors of Lafargue, guided also by the tentatives made by Ferguson and Pravaz in the radical cure of varices by coagulating injections, Wood proposed the use of the now em- ployed for the introduction under the skin of medi- cinal substances, and in 1859 my regretted master* Behier, made known all the advantages which accrue to the hypodermic method. You know to-day the uses as well as the abuses of subcutaneous injections, and what advantages we derive from them There is no pain so stubborn as to resist this medication, and we can affirm that by its means we always give relief to our patients. An Irish physician by the name of Rynd has disputed with Wood the priority of the discovery of the hypodermic injection, claiming that in 1841, that is to say, almost ten years before Wood published his memoir, he was in the habit of treating sciatica by hypodermic injections. But, when you read atten- tively Rynd’s article, you perceive that he was not the 12 inventor of the subcutaneous method from the point of view of the introduction of calmative medicaments such as morphine, but rather from that of injections for local effect, which our colleague, Dr. Luton, of Rheims, was the first to practice in 1869, and to which in 1875 he devoted his able treatise on subcutaneous injections for local effect. In fact, Rynd employed to cure sciatica a mixture of morphine and of creosote. I cannot here, gentlemen, point out all the advant- ages of the hypodermic method. Applied first to the introduction of calmative medicaments, this method was soon generalized, and you know to-day that it is the only sure means of introducing medicinal sub- stances, and if we are now seeking with so much care to find the active principles of medicines, it is in order to put in practice this mode of introduction. To all these new means of cure has been added the discovery of a substance which by its action on the bulbus and the entire cerebro-spinal axis was des- tined to render immense service in the treatment of nervous affections, and enable us to cure epilepsy in half the cases; I refer to bromide of potassium. In 1826, Balard discovered bromine; two years afterward (in 1828), a Fellow of the Faculty of Mont- pellier, Pourchet, applied bromine, or rather its com- bination with potassa which he called hydro-bromuret of potash, to the treatment of scrofula and goitre, thus substituting, by an effort of reasoning easy to understand, bromine for iodine, its congener, the first 13 application of which to therapeutics was made several years before (in 1820) by Coindet, of Geneva, who was, thus, the creator of the iodide medication. It is this same idea that inspired the attempts made long afterward, from 1840 to 1850, by Puche and Ricord, in the Hospital du Midi, to substitute bromide of potassium for the iodide in the treatment of syphilitic affections, which tentatives served as a basis for the theses of Rames of Aurillac, and of Huet, of Montargis, theses approved in 1850. The year following, in 1851, Locock, taking a hint from a fact communicated in 1840 by a German physician, Otto Graff, relative to the anaphrodisiac properties of bromide of potassium, applied for the first time this medicament to the treatment of certain neuroses, in which he thought that the genital sense played an important part. The marvellous results which he obtained in epilepsy, results soon verified in France, laid the foundation of the bromide medica- tion, which now occupies so large a place in the therapeutics of nervous affections, that we ask our- selves how we could get along without this precious medicament. You see then, gentlemen, that the art of healing, or more strictly speaking, the art of relieving pain, has in a short space of time profited by five important discoveries. In 1846 occurred the discovery of ether- ization; in 1847, the application of chloroform to medicine; in 1851, the application of the bromide 14 medication to the treatment of neuroses; in 1853, the introduction of the hypodermic method into thera- peutics; in 1869, the discovery of the hypnotic action of chloral. While progress was being made in this direction, new horizons were opened to therapeusis by the discovery of a series of bodies which the industry of the chemist has succeeding in extracting from the residue of the fabrication of coal gas. I allude to the phenols and oxyphenols. Here, too, it was not pure empiricism which led to these discoveries, but they were the result of two grand factors; on the one hand the new views which Pasteur had put forth respecting the nature of fer- mentations, and on the other the incessant progress of chemistry. The new ideas on fermentation show us its analogy with putrefaction, and especially the predominant role of micro-organisms in these phe- nomena, and finally the capital importance of anti- septic substances in preventing the development of these proto-organisms. All these discoveries threw a new light on the pathogeny of accidents complicating wounds, and it is easy to understand the zeal with which surgeons pressed into this new therapeutic path, and with an enthusiasm the greater from the fact that chemistry had just discovered, as a result of the distillation of coal and the analytic decomposition of tar, a new series of bodies to which was given the name of aromatic series. 15 I took part in the first trials with these products, and the observations which, while in the service of Velpeau, whose interne I then was, in 1859,1 collated concerning the power of coal tar, recommended by Cocne and Demeaux, helped to make the report which my illustrious master some time after presented to the Academy of Medicine. The action of the coal tar was not at all doubtful, but the question was often asked if these effects were not due to some principle in the tar rather than to the tar itself, and this led to the employment of phenic or carbolic acid, which Runge in 1834 had extracted from tar, and to which, as being a by-product of the fabrication of illuminat- ing gas, he had given the name of phenol from the Greek 0aivoo, “ I illumine.” Lemaire in 1861 was the first to show the useful applications which might be made of phenol, and from this time we have seen medicine and surgery employ all the bodies which are derivable from these phenols and from their combina- tions, and successively salicylic acid, kairin, resorcin, etc., have been brought before the profession. But the internal application of these phenols and oxy- phenols showed us that these antifermentative medi- caments all possess a very important property, that of lowering the temperature, thus assimilating the febrile process to a process of fermentation, and thereupon a new group of antithermic medicaments was consti- tuted. This class of antithermic medicaments, to which 16 I shall shortly devote a whole chapter, has in our day assumed a capital importance. Since the introduction of the thermometer into clinical practice, and since the custom was established of daily noting the cyclical march of diseases by the careful observation of the thermometer, a considerable importance has been attached to the temperature in diseases, an importance which has perhaps even been exaggerated, and there is a tendency always to en- deavor to bring back to the normal the inordinate temperature of fever patients. You will see that we can attain this end by the employment of medica- ments the discovery of which is quite recent, and with which we can lower at will the febrile hyperthermia. Among these medicaments, there is one which, by its special action in rheumatism has a rank without a peer; I allude to salicylic acid. It is to Strieker, in 1876, that we are indebted for the first exhibition of salicylic acid in rheumatism; the application in this case was, I am aware, absolutely empirical. From time immemorial, the infusion of willow bark had been employed in the treatment of rheumatism; the dis- covery made by Leroux in 1827 of salicin had been applied only to the treatment of intermittent fevers, and when Strieker proposed to treat rheumatism with salicylic acid, it was a notion absolutely empirical which guided him. Moreover, we are still ignorant of how this medicament acts, while recognizing its marvelous efficacy, since in the immense majority of 17 cases, it causes disappearance of the atrocious pains and fever provoked by acute articular rheumatism. Such, gentlemen are the precious acquisitions of therapeutics the last fifty years. To all such as may deny that therapeutics has made progress, it will be sufficient to point to the facts I have just indicated, and it will be made plain to any unprejudiced person that therapeutics, like the other branches of medicine, has not failed to make great gains. Let us indulge the belief, however, that this is but the beginning. The discoveries of our illustrious countryman whom the entire scientific world has lately so signally honored at Edinburgh and at Copenhagen, are but a foretaste of future gains, and when I look at the rapid progress that is being made in researches of this kind, and when I think of the revolutions which the art of medicine is destined to undergo as a result of the more complete knowledge of the micro-organ- isms, and of inoculations of attenuated virus, I am ready, in my turn, to exclaim: “ Happy are our young men, for great things are in store for them.” CHAPTER II. ON NEW CARDIAC MEDICAMENTS. Gentlemen: I shall devote this lecture to a consideration of the new cardiac medicaments, and by that word new I mean medicines which have been introduced into therapeutics the past five years. Three new medicaments have been recently brought into repute in the treatment of heart diseases, and it is to these chiefly that I shall call your atten- tion : convallaria, caffeine, and trinitrin; the two first being applicable to mitral affections and acting as tonics to the heart; the third, on the other hand, being chiefly of use in diseases of the aortic orifice and aorta. This distinction between mitral and aortic diseases, from the standpoint of therapeutics, is one which I endeavored to establish in my work on Diseases of the Heart, and seems to-day to be generally admitted.* You know that from the point of view of treat- ment I have maintained that it was necessary to make a marked difference between mitral and aortic affec- tions. In the first we must endeavor to augment the force of the heart to make it equahtoits tasks, and we attempt this by means of the group of medicines known as tonics of the heart. In order better to mark * Diseases of the Heart, Part I. Published by Geo. S. Davis, Detroit, Mich. 19 the time when the cardiac tonics are of the most ser- vice, clinicians have divided into several periods the cycle which the heart affection traverses, from the simple lesion of the orifice to the cachexia, and Fernet and Huchard have characterized these periods by a peculiar name. In the first period, to which they give the name ensystolic, there is lesion of the orifice with- out alteration of the myocardium; hygienic means are alone of utility in this period. In the second period, which they call hyper systolic, cardiac hypertrophy comes in to compensate the troubles due to the lesion of orifice, and here, too, hygienic treatment suffices. In the third period, called hyposystolic, the equilibrium is broken, the compensation is insufficient, the tonics of the heart are necessary. In the last period, called asystolic, the heart is affected with fatty degeneration, there is, as Gubler says, cardioplegia, and the most energetic of our cardiac tonics, caffeine perhaps ex- cepted, become impotent to combat this state.* In diseases of the aortic orifice, therapeutics must be directed differently, and we are now concerned with combating the two symptoms which result from lesions of this orifice, namely, the cerebral anaemia and the irritation of the nerve plexuses which surround the aorta, and it is here that the medicaments which * Fernet, on Digitalis in Diseases of the Heart (Bull, et Mem. de la Soc. de Therapeutique, 1882). Huchard, on Caf- feine in Affections of the Heart (Bull, de Ther., ciii, p. 145). 20 stimulate the cerebral circulation, and those which diminish nervous sensibility, find their application. It must be understood that this distinction in treatment is only applicable to one phase of diseases of the heart, and that in the case of affections of the aortic orifice—insufficiency, for example—there ar- arrives a moment when, in consequence of dilatation of the heart, there is mitral insufficiency; then all the troubles which characterize this latter disease appear, and tonic treatment is imperatively needed, together with those remedies that favor the cerebral circulation and relieve distress. As for the tonics of the heart, digitalis deserves the first place; next in importance (strange to say) comes bromide of potassium, as I have shown in my Diseases of the Heart; next in order we should now add convallaria and caffeine. CONVALLARIA MAJALIS. Convallaria majalis (muguet; lily of the valley) is a plant with rhizoma, which grows in abundance in our woods, and which presents at this very moment its racemes of odorous white flowers. The first anal- yses of this plant were made in 1858, by Wals, who found there two glucosides, convallamarin and con- vallarin. In 1865, Marmet studied the physiological action of these two glucosides, and, according to him, convallarin is purgative, and convallamarin toxic. In 1883 Ernest Hardy, then M. Tanret, each inde- 21 pendently, perfected the mode of extraction of these two substances. In China, the inhabitants make use, as a succulent vegetable, of the young shoots of a species of conval- laria, Polygonatum Japonicum, which has with them much the same place as asparagus has with us. In Russia, the natives employ as a diuretic, another species of convallaria, the Convallaria polygonatum, so well known in our woods under the name of Solo- mon’s Seal; such use of this plant, probably, first led the Russian physicians to make trial of the lily of the valley in heart affections. I say first, for it is probable that the Russian physicians did not know that in the middle of the 18th century (1745), Car- theuser, the celebrated physician of Frankfort on the Oder, in his rudiments of Materia Medica, mentions among the numerous properties which he ascribes to the lily of the valley, that of calming cardiac palpita- tions, and of toning up the weak heart, and that Fer- rein, in 1770, mentions, also, the diuretic properties of convallaria. In his recent thesis on convallaria, Nog- ues has clearly proved the priority which is due to Cartheuser.* Ernest Labbee has, however, shown still more recently that Matthiolus, in 1580, in his communications of Dioscorides, refers to the lily of the valley as being very beneficial in palpitations; “ it fortifies the heart,” he says.f * Cartheuser, Matures Medicales. Ed. 1745, Perrien, Matures Medicales, 1771. Nogues, These de Paris, 1883. f Ernest Labbee, Du Convallaria Maialis (Gaz. Hebd. June 13, 1884), 22 However this may be, all these facts had been forgotten when appeared the first researches, made under the inspiration of Botkin and his pupils, Bogo- javolenski and Troitzi. Bogojavolenski pointed out, in 1880, the results obtained by the employment of convallaria. Also Isai- eff, Kalmikof, in 1881, Troitzi, in 1882, D’Ary, in 1881. And finally Germain See, in 1882, repeated these ex- periments, which he completed by new researches, and made known the advantages which we may derive from, the employment of this medicament. The researches of the Russian physicians, those of Germain See and of Bochefontaine, and those still more recent of Coze and Simons, have shown that in animals, and especially in cold-blooded animals, the divers preparations of convallaria, have a real tonic action on the heart. The sphygmographic tracings which these last two experimentors have furnished, show that not only convallaria diminishes the number of pulsations, but that it does this while augmenting the amplitude of the contractions. It is to this period of slowing and augmentation of amplitude that these experimentors have given the appropriate name of the therapeutically useful period of convallaria, and when you compare this useful period with that which be- longs to digitalis in like doses, it is found that the superiority is to be assigned to convallaria. From the standpoint of its action in man, this medicine is proven to be one of the most powerful diuretics known, and Prof. S6e ranks it before digi- talis. It is applicable, then, especially to mitral dis- eases with dropsy; at the same time, it is well to make this reserve, that when there is albuminuria, the diuretic action is considerably lessened. Convallaria calms also the palpitations and dis- orders of the heart which are purely functional in character, and if I add that the preparations of this medicament have no toxic action in man, I shall have pointed out their principal advantages. Since the labors of the Russian physicians, and especially since the communication of Prof. See, there have been a multitude of trials made with convallaria, and we know to-day, thanks to this experimentation, the true value of this medicament. In Germany convallaria has had but little success, especially if we ai*e to judge by the article published by Stiller, who, in twenty-one cases of affections of the heart where convallaria was employed, saw no positive results, except in two cases.* In America convallaria seems to have had better results, as you will see by referring to the communi- cations made by my excellent friend, Dr. Hurd, of Newburyport, and Drs. Beverly Robinson, Taylor, Polk, Smith,f and others, all of whom have had suc- cess with this medicament. 23 *Stiller, Versuche iiber Convallaria Maialis bei Herzkrank- heiten (Wien. Med. Woch., No. 44, 1882). fTherapeutic Gazette, 1883, p. 283, also pp. 365, 126 etc. See also Medical Record, vol. 23, p. 413). In France, if we can base our opinion on treatises published since the communication of Prof. S6e, and discussions before the Society of Therapeutics, it is plain that if the profession is agreed in admitting the diuretic effect of convallaria, the action of this medi- cament is nevertheless regarded as very uncertain. This is the view very clearly expressed by Peter in his Clinical Lessons on Diseases of the Heart; by Constantine Paul, in his late work;* and it is also my conclusion. In fact, in the numerous trials which I have made of convallaria, I have sometimes met with success—in a small number of cases it is true,—but very generally with failure. Despite this uncertain action, however, I believe that we do well to continue prescribing this tonic of the heart, because it is per- fectly safe, and because it can be utilized at such times as we are obliged to leave off the administra- tion of digitalis. You know, in fact, that everybody is agreed at the present day in the expediency of not giving the preparations of digitalis continuously, and in interrupt- ing for a certain time treatment by digitalis, to renew it again after a suitable interval. It is during this period of suspension of the foxglove that you can employ convallaria, taking care, of course, not to attribute all the diuretic effects thereafter obtained to this medi- cine, for, as you know, the action of digitalis on the 24 *On Diseases of the Heart. Published by Wm. Wood & Co., Medical Library series, 1884. 25 kidneys is prolonged for some time after you cease its administration. How and in what dose shall you give convallaria? All parts of the plant, flowers, leaves and root, have been employed. The more active parts are the flow- ers; then the leaves; the plant may be used in the fresh state in the form of alcoholic extract, or in the dry state, as tincture or as extract. The infusion is an untrustworthy preparation. The extract is gener- ally used; that may be either fluid or solid; that made from the flowers and the leaves is preferred. I here place before you the various extracts of flowers and leaves, which have been furnished me by M. Adrien, and you observe that they are of brilliant black ap- pearance, of a quite peculiar bitter savor, and soluble in every proportion in water and in alcohol. A good diuretic mixture, of which a tablespoonful three or four times a day may be given, may be made by rub- bing up a couple of drachms of the extract of the flowers and leaves, in eight fluidounces of decoction of broomtop. The American fluid extract made by Parke, Davis & Co., is quite a reliable preparation. I here show you a sample. You remark that it has per- ceptibly the odor and taste of the flowers. The dose of these liquid extracts is from ten to thirty drops, three times a day. The dose of the solid extracts is about ten grains, but the extract prepared from the root is very much weaker. Whatever form you may choose, do not count on obtaining certain results, and be prepared for disappointment. 26 Quite different is the preparation of which I am now to speak. Caffeine is, in fact, one of the best tonics of the heart, and in the last stages of cardiac affections it will render you more service than digitalis. Extracted for the first time in 1820, by Runge, ob- tained under the name of theine, from tea, in 1827, and in 1840 by Martius, from Paullinia sorbilis, under the name of guaranine, also from Paraguayan matt, under the name of mateine, by Stenhouse in 1840. caffeine, which has an atomic formula of C8H10N4O„ may be got from these different substances, to which we may add that precious fruit on which we are ex- perimenting this moment in our hospitals, and of which the negroes of Central Africa make so great account, kola (Sterculia kola), and which contains, as has been shown by the researches of Heckle and Schlagdenhaufen, caffeine and theobromine, and which has even more caffeine than coffee; the last, in fact, con- tains from 70 centigrammes to a gramme and a half in every hundred parts, while kola contains twice as much. Caffeine presents itself under the form of a white crystalline salt, soluble in 90 parts of water. As Tan- ret has shown, its basic properties are very weak and there does not exist properly speaking, either acetate, citrate, valerianate, or lactate of caffeine. The brom- hydrate and the ehlorhydrate appear in the form of beautiful crystals, which are however, insoluble. CAFFEINE. 27 Tanret, therefore, has proposed a more stable combi- nation of caffeine with salicylate or benzoate of soda. The first contains 45 per cent, caffeine, the second 61 per cent. These combinations being quite soluble, and having no local irritant action, may be used by the subcutaneous method. These are the formulae which Tanret has proposed. 5 Benzoate of soda, 2.95 (gr. xliv). Caffeine, 2.50 (gr. xxxvj). Distilled water, 6.00 (gr. xc). M. Fiat solutio. Each syringeful, or about 15 minims, contains a full dose of caffeine. (In other words, a cubic centi- metre [about 20 drops] has 25 centigrammes.) The second formula is as follows: B Salicylate of soda, 3.10 (gr. xlvij). Caffeine, 4.00 ( 3 j). Distilled water, 6.00 ( 3 jss). M. Dissolve with the help of heat. Each cubic centimetre contains 40 centigrammes caffein. You need, however, resort to the hypodermic method only in exceptional cases, as when the patient is taken with vomiting, or when the caffeine provokes gastric irritation and pain. Ordinarily the caffeine may be given in pills, in granules, in capsules, or in potion. The pill form is not much employed. This re- sults from the fact that the pills may pass through the intestinal tube without undergoing solution and ab- 28 sorption, or the absorption may be incomplete, which is a disadvantage, seeing that caffeine is dear. The granules are good preparations, but are open to the same objection, and to get the full benefit of them large doses must be given—even two grammes ( 3 ss) a day. As for the capsules, this is an excellent mode of administration, and you may prescribe in this form doses of from 25 to 50 centigrammes (4 to 8 grains). They have, however, the inconvenience of causing distress in the stomach (one of the disadvantages of caffeine in concentrated form). Therefore, I prefer the liquid form, giving the medicine with a large quantity of the fluid menstruum. You may, for instance, give three times a day a ten-grain dose of caffeine (pretty large doses are necessary, as I shall tell you hereafter); this may be given along with ten grains of benzoate of soda, a little syrup, and enough fennel or peppermint water to make up three or four ounces. The following formula may be more convenient for private practice: 9 Caffeine, 7.00 (gr. 105). Benzoate of soda, 7.00 (gr. 105). Water, 250.00 ( § viij). M. Each tablespoonful of the above mixture contains about 50 centigrammes (or 7 grains) of caffeine. Leaving one side all which does not concern the action of caffeine on the circulation, I shall take up 29 this aspect of the question, and shall now consider the physiological effects of caffeine on the heart. When you take a glance at what has been written relative to the action of caffeine and of coffee on the heart, you observe that the opinions may be ranged in three groups; some, as Gentilhomme, of Rheims, claiming that caffeine has no action on the heart; others, as Trousseau, Rognetta, Dettel, etc., that it accelerates the pulsations of the heart; others still, notably, Caron, Meplain, and Foussagrives, that it slows the pulsations of that organ. Whence comes this diversity of opinions? It re- sults from this fact, which is applicable to so many of the tonics of the heart, that the toxic effects are absolutely opposed to the therapeutic effects, and while caffeine in moderate doses (as Giraud and Leb- lond have proved)* diminishes the pulsations while augmenting the vascular tension—i.