Talk:The Johns Hopkins Medical Journal 5 (1894)

By Hunter Robb, M. D., Associate in Gynmcology. \_Read before the Johns Hopkins Hospital Historical Club, April 9, 1894.]

Marie Anne Victoire Boivin, the famous midwife, was born ill 1773 and died in 1847. Although her early education was not very complete, she must have made up for any deficiencies later on, for she was not only a voluminous writei", but her writings show a careful study of the subjects taken in hand. She was in the Maternite, in Paris, from 1797 to 1811, where among others she had for her instructors Lachapelle and Chaussier.

In her work entitled " Memorial de I'art des accouchements," first published in 1813, and which had reached its third edition in 1824, she expounds the methods which were in i;se in the Maternite. The book, however, aroused the jealousy of Lachapelle, who comijelled Boivin to give up her position. But by this time Boivin had attained to some celebrity, and she found a congenial field of work in the hospital of Poissy and the Maison de Saute, during which time she found leisure to translate some of the English writings upon gynjccology, and to write a monograph on " Hemorrhages of the Uterus," which was awarded a prize.

Later on she published 2)apers on " The Vesicular Mole," on Abortion, on the Measurement of the Pelvis, and upon Cffisarean Section. Associated with Duges, a nephew of Lachapelle, she was the author of a work in two volumes entitled : " Traite pratique des maladies de I'uterus et de ses annexes." This work was published in Paris in 1833, and was afterwards translated into English by G. 0. Hemming, who was consulting obstetrician to the St. Paucras Infirmary. She also appears to have written some other monographs and to have translated several works, among them a treatise by Barron on the subject of Tuberculosis.

On account of her writings she was given the honorary title of Doctor of Medicine by the University of Marburg.

Her " Memorial de I'art des accouchements " was written, as we have said, while she was at the Maternite. She began il:, she says, for her own benefit, and made drawings of the different positions of the foetus, principally for the instruction of her niece, who had the intention of becoming a midwife, ik'ing surprised by Chaussier while engaged in this work, and IiL'ing asked by him whether she would not be willing to publish it, she replied that the main difficulty lay in the great cost of reproducing the plates, and that without these she thought that such a book would be comparatively useless. Upon this Chaussier oiTcred to take the expense upon himself, for which great liberality she expresses her gratitude in the preface to the first edition.

The second edition contains nuiny chapters which were not in the first, notably those on the Circulation of the Blood in the Fo'tus, on the Nutrition of the Fretus, on Artificial and Natural Deliverance, on the Care of the Woman before, during and after Labor, and on the Care of the Newborn Infant.

" The precepts contained in this work are," she says, •■ I'ciunded on the practice of the Hospital of the Maternite and on those of the most celebrated practitioners of our own

as well as of foreign countries. We have had recourse to our own experience only in those cases where more reliable authorities have been wanting."

The criticism of the General Council of the administration of the civil hospitals of Paris on the work is perhaps as good as can be found, and we therefore give a brief abstract of it. The Commissioner says : " All treatises on Midwifery are composed essentially (1) of the anatomical and physiological part necessary for the better comprehension of the development of pregnancy and the mechanism of labor; (2) of a part which explains the mechanism of natural labor, notes the different obstacles which are opposed to its course, rendering it more or less difficult, and indicates the proper means by which these are to be remedied ; (3) of a description of the conduct of labor."

" The first part is treated in this work excellently and systematically. All the parts referring to pregnancy and labor are written with great clearness and precision, as also are those treating of the development of the embryo and of the foetus. One sees with pleasure that Madame Boivin possesses a thorough knowledge of her subject. The mechanism of labor, which is the foundation and the key of the whole art, is well described. The third part, namely that which ti-eats of the conduct of laboi's, is generally taught by means of a machine, or sort of manikin, which represents the woman in labor. It is the custom to demonstrate to the pupils all the possible positions which the child can occupy with relation to the canal through which it has to pass, and these the pupils are made to practice on the manikin. The different positions and the manipulations which they demand form the most important part of her work, and it is just this which distinguishes it from the elementary books upon the art of midwifery. They are set forth in 133 plates, but after what I have just said it is easy to judge that this work ought to be more useful to those who have already finished their course than to those who are commencing it."

A footnote by the author says: "It was this last remark which determined ]\Iadame Boivin to make additions to the book, so that it might be equally useful to those who were beginning as to those who had ended their course."'

A\'e shall say very little more about the work itself. In speaking of the nourishment of the fcetus she gives some very interesting experiments of Chaussier which were made to prove that the uterine vessels commuuic^>ted, although indirectly, with the umbilical vein.

In speaking of the different presentations she refers to Baudelocque's statistics, which contained 20,517 births. She also gives a fcible of cases reported by Dr. Samuel Merrimau. accoucheur of the General Dispensary of Wostmiustor, of the Jliddlesex Hospit^d, and of the Infirmary of St, George's Parish in London. This table is taken from his work which is entitled " A synopsis of the various kinds of difficult parturition." Every possible position is illustrated in the

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plates at the end of the book, and there are also figures which serve to illustrate the use of the lever and of the forceps, as well as showing the other different manipulations.

The book closes with the aphorisms of Mauriceau, who was an obstetrician of the 17th century, and of those of Orazio Vallota, the latter of which she translates from the Italian. Of these we shall not speak now, as we are dealing with the original works of Boivin.

This smaller book which I now show you accompanied by a German translation, was published in Paris in 1828, and is entitled " Researches on one of the most frequent and least known causes of abortion," followed by a monograpli on the pelvimeter. The work, which was commended by the Royal Society of Medicine of Bordeaux, consists of careful notes on a number of cases, some of which came to autopsy, and its purpose is to refute the opinions of those who held that "pregnancies, abortions and difficult labors are the most frequent causes of diseases of the uterus." " On the contrary," says Boivin, " it is the diseases of the uterus, and even more often those of theadnexa, which are the cause of abortion and of premature labor. (3) Among the many women whom we have seen suffering with diseases of the uterus, many confessed that they had had abortions, but very few had met with difficult labors." In an interesting footnote she adds: "At the moment of writing these pages I was consiilted by the wife of a druggist, aged 23, in whom on three successive occasions labor had come on at the end of seven mouths. During the course of the two last pregnancies she received the intelligent aid of Professor Gardien; but in spite of this, and i n spite of general blood-lettings (repeated four or five times) and absolute rest, the labor came on in the seventh month. In. this case we found upon examination that the adncxa on the right side were adherent to the uterus."

This, then, is the most important proposition in the work, and we will content ourselves with a short summary of the conclusions at which she arrives. (1) Abortion is often the result of an organic lesion of the uterine adnexa, and these diseases are not, as is generally supposed, oftpn caused by abortion. (2) Such lesions are seen more often than one would think in young patients. (3) They are generally due to a chronic phlegmasia, to irritation, or to the formation of accidental tissue which exposes the parts to an acute infiammatiou. (4) Such conditions are often brought about by neglect of the laws of hygiene. (5) The germs of these affections are seen in girls who are weak, of a lymphatic temperament, or of a scrofulous constitution, who are troubled with habitual constipation or diarrhoea, who have a bluish sclerotic and long eyelashes. (0) With these last menstruation is premature and seldom regular. Leucorrho'a and constipation are ordinarily the cause of these diseases, but often these causes become effects. (8) Since the symptoms of this disease can easily be mistaken for those of another affection, the rational method of diagnosing such conditions is by careful examination. (9) The examination of the genitals should be made with the greatest care, and it should be especially noted whether tlie organs are fixed or movable. When the uterus is bound down, if conception takes place, abortion will result. (10) Adhesions of the peritomvum to

the surface of these organs hinder them from changing their position in the normal manner. (11) Marriage, which is so often recommended for this condition, in the majority of cases instead of curing, acts as an exciting cause of diseases of the uterus. (12) When only one tube or ovary is diseased, conception can take place, and can even go on to term. (13) But abortion will almost inevitably result, if the adhesions, no matter what their nature be, are extensive, because they bind down the uterus and do not permit it to expand. (14) Such abortions are very generally followed by grave accidents, by hemorrhage, metritis, peritonitis, ulceration, sometimes even by gangrene of the parts affected, and death. (15) At other times, ulceration follows abortion, and if the abscess breaks into the peritoneal cavity, the result is fatal for the patient, but if it discharges through the vagina or rectum she may recover. (16) One cannot judge of the condition of the uterus by the appearance of the ntero-vaginal orifice. (17) The disease sometimes extends to the adnexa, but on the other hand sometimes it is at first limited to them and progresses from within outwards. (18) When the ovary is diseased, but is not bound down and can extend into the abdominal cavity, it may happen in such cases that the uterus preserves its normal situation and its natural volume. Sometimes when the ovaries and tubes have increased in volume we find an atrophied uterus. (19) Fatal accidents are less common when the diseased adnexa are not bound down. We may have, however, compression of the lungs, and ascites. (20) Cyst of the ovary is only dangerous in itself when it has attained a considerable volume. The patient, however, generally succumbs to exhaustion. (21) In pregnancy the umbilicus goes towards the middle regions of the abdomen instead of descending towards the pubes, as it does in case of abdominal tumors and in ascites. (22) Many of these diseases can be prevented and many patients can be saved by an early diagnosis.

The second series of cases are instances in which diseases of the ovaries have been mistaken for pregnancy. In speaking of the operations which have been practiced for diseases of the ovaries, she takes the opportunity of translating into French a letter on a case of successful extirpation of the ovary, addressed to a citizen of Philadelphia by Alban Ci. Smith, M. D., of Danville in Kentucky, fcjhe follows to some extent the literature on the subject of these operations and mentions McDowell's cases, (luoting from the " Eclectic Repertory." She mentions the case of Dr. Nathan Smith, whuh was recorded in the Edinburgh Medical and Surgical Journal, as well as four cases of j\I. Lizars. Quoting from a number of the same journal in 1825, she says that the English are not in favor of this operation, and credits the editor of the "Review" with the following remarks: "It is impossible to believe that such an operation has ever been performed with success, and we do not think that one should ever undertake it." For herself she says : " We are more credulous than the author of the article in the Medico-Chirurgical Review; not mily do we believe that the operation has been attempted, but that it has been performed with success, because there are circumstances which accompany diseases of the ovaries which permit us to believe in a sort of cure; but since these favorable con

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ditions can never be known until after the operation has been begun, the attempt we must admit savors of rashness, and the success obtained could not guarantee a lasting security. It is true that gastrotomies, gastro-hysterotomies, and other operations where the peritonanim has been opened, have often been attended with favorable results, and accidental wounds of the abdomen have frequently gotten well, but it must be remembered that disease of the ovaries which is not caused by abnormal pi'eguancy is almost always the result of some constitutional affection and of a scrofulous or cancerous idiopathy. In these latter cases, therefore, the resistance of the patient is diminished." She concludes by saying that such operations might prove more successful on savages and negresses, who from suffering in a state of slavery are almost indifferent to what would be fearful pain to Europeans, who have arrived at a high condition of civilization, and are consequently much more sensitive. In the case of the latter, she doubts whether such operations will be found to succeed as well as in that of " those poor wretches who are obliged to submit to the commands of the master who orders them to be disemboweled just as he orders them to work."

In the same volume is found a description of a new pelvimeter with accompanying plates. The chief advantage claimed for her instrument is that by its use great accuracy is obtained, since one arm is inserted into the rectum and thus rests upon the sacro-vertebral articulation.

We have referred somewhat at length to this one of the less important writings of Madame Boivin, but we now come to what is perhaps her greatest book, which, as we have said before, she wrote with the assistance of A. Duges, a nephew of Lachapelle, and which is entitled " Diseases of the Uterus and its Appendages." The very fact that the book was published as late as 1834, and was written in conjunction with a man who was a well-known writer and a professor of the faculty of medicine of Montpellier, besides possessing many other titles, would have led us to expect that we were dealing with a comparatively modern book on the subject of gynecology, and one which was fully abreast, if not ahead, of the times in which it was written. In fact, twenty years ago it might well have passed as a modern text-book, and it is only since bacteriology has introduced so many changes in the technique, and has consequently rendered more common and less dangerous operations which in Boivin's time were but rarely attempted, that her work has become really antiquated. ^V^hatever treatment she may have received from the hands of Lachapelle, it is evident that she bore her no illwill, since the work is dedicated "to the memory of Madame Lachapelle, our first guide, our first teacher, the object of our common affection during life, of our admiration and of our regrets after her death," and to M. C. Dumeril, who was the physician in chief to the Maison Royale de Sante.

All through the book it is evident that the literature of the subject has been thoroughly worked up, and all the important writers and their opinions are quoted in its pages. The French version with its numerous clinical cases is at times si little tedious, and we have therefore found it more agreeable to read the English translation by llennning, this being admirable, and the footnotes which he adds being full of iuterest. more

especially as he quotes frequently such men as Marshall Hall, for whom he had a profound respect and to whom he dedicates his translation. It is not necessary, then, to go through the work in detail, but it is still well worth reading. We will only mention a few minor points which for some reason or other especially attracted our attention. One point in connection with the use of the drainage tube struck us more pai'ticularly on account of the disfavor into which its employment has lately fallen. In her chapter on wounds of the uterus, after speaking of a gunshot wound caused by a bullet which killed the child in utero, but which did not prove fatal to the mother, she speaks of a case in which the uterus had been penetrated and which was drained by means of a tube. She says that the tube remained in for some time, and the wound continued to discharge freely until one day, as luck would have it, the tube was forgotten and the wound very quickly healed.

Iler subject is divided almost in the same way as in the modern text-hooks.

Of extirpation of the uterus she says, after speaking of the occasional necessity for it in prolapsus and inversion, that the operation of total extirpation is so formidable it will probably be ultimately interdicted in those cases in which the uterus is in its place.

She then goes on to mention two cases of hysterectomy performed by ignorant persons which proved successful, and several by skilled men, all of which were appai-ently fatal.

Her chapters on fibroids, polyjii and cancers are in accord with the best teachings of those times. Of cancer she says : " The term cancer has been expunged from the vocabulary of pathological anatomy, owing to the want of precision in its use. By cancer we shall designate every affection which by converting in its progress the texture of the uterus, has a natural tendency to increiise, to propagate itself on all sides, and ultimately to be itself destroyed by ulceration beginning at its centre. AVe shall hereafter distribute them into four chapters under the titles of the scirrhous, the fungous, the ulcerous, and the ha?matode."

In her chapter on puerperal fever she says that the causes are still unknown. "Cold operates more frequently as the occasional rather than the exciting cause, but all the facts go to refute the so-called humoral pathology."

She speaks of the success of ergot in hemorrhages of the uterus, but says it is diflicult to state what are the piirticular cases in which it should be used. She discusses the two contradictory opinions which existed as to the origin of hysteria, and although she agrees that the theory that hysteria proceeds from a disease of the brain is not unreasonable, she thinks that as the state of the uterus so distinctly modifies the nervous symptoms, its primary and real source may be fairly txaced to that organ, especially when we consider that undoubted though slight hysteria always exists at the time of the menopause."

She describes minutely various paroxysms, (1) suffocating paroxysms, (2) apoplectic paroxysms, (3) syncopal paroxysms, (4) cardiac paroxysms, (o) pertussiform paroxysms. Of the fourth variety she gives two examples, one lieing the case of no less a person than Madame LachajvUe herself. "Madame Lachapelle was affected with symptoms which had been

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attributed to aneurism of the coeliac artery, and spasmodic dysphagia, which in one of her attacks almost precluded the use of food and drink for fifteen hours. In 1812 the case assumed the form of palpitations accompanied by dyspnoea, excessive anxiety and extreme debility, with general trembling and oppressed respiration.. These symptoms were always attended by a profound sense of coldness, alarm, and apprehension of aneurism. After continuing for a quarter or for half an hour the paroxysm subsided, and repeated eructations announced its termination."

She gives nothing new or very strange for the treatment, but says that the cough can be cured by the syrup of morphine, a therapeutical hint of doubtful value.

In speaking of diseases of the ovaries, she raises the question whether it would not be safer and easier to remove a diseased ovary through an incision in the vagina. She cites a case of labor during which a scirrhous ovary came down and projected from the anus together with a portion of the rectal wall ; this was cut off and the woman died. But she questions whether, if the case had not been complicated by the labor, and the incision had been made through the vagina, the result would have been equally fatal.

She devotes separate sections to diseases of the Fallopian tubes and those of the ovaries. In speaking of the ovaries she again mentions the operations of N. Smith and Ephraim McDowell of Kentucky, and after giving vario'us others, reaches the following conclusion : "There are then 15 cases of

this operation, namely extirpation, of which 6 have been attended with at least temporary success, 5 with neither good nor bad results, and 4 with death. In five cases the operation could not be completed. Extirpation will therefore be indicated only when the diagnosis is distinct; when the mobility and recent date of the tumor preclude the probability of adhesions, and when the absence of hardness after examination by puncture removes all fear of serious complications. Even then we should hesitate, but if we do decide upon the operation, the incision should be as small as possible, the sac should be first evacuated by inmcture and afterwards drawn out in its empty state."

Several pages are devoted to injuries and inflammations of the pudenda. She recognizes three kinds of lacerations of the j)erinseum, the anterior, the central or posterior, and the complete laceration. She concludes by giving cases of ffecal fistula which opened through one of the labia majora.

The plates which accompany the book are excellent.

We do not pretend in this short paper that we have done full justice to the works of Madame Boivin. It is evident that she not only understood her subject, but she also knew how to write lucidly. Even if her own modest assurance is true that her works contain little that is original, at any rate we owe her a great debt of gratitude for collecting and jiutting in a readable form the combined knowledge of the majority of the principal authorities of her time.

BARON VON LANGENBECK, SURGEON-GENERAL OF THE GERMAN ARMY, PROFESSOR OF SURGERY IN THE UNIVERSITY OF BERLIN.

By AValter B. Platt, M. D. [Read before the Johns Hopkins Hospital Historical Society, April 9, 1891.]

Among the surgeons of the pi'esent century who by noble thoughts and acts inspire their pupils with, unbounded admiration, there is none who has received and deserved more than Bernhard von Langenbeck, both on account of his great professional achievements as well as by reason of the rare personal qualities, which were those of a leader of men. The one made him far and away the first surgeon of his day in Europe; the other, a man most beloved by his pupils, patients and colleagues.

To how few are these qualities granted! United with stability of purpose, they must produce a certain result. This is seen throughout his intensely active and useful life. It was my rare good fortune to know him, to see and hear him often, to meet him frequently at his own house.

'J'he impress of his character will remain indelible. In looking over the enthusiastic and almost tearful notices written in different parts of Europe by his many pupils soon after his death, the same impression seemed to have been made upon all. There was the greatest admiration of the man as well as of the brilliant surgeon.

On the shores of the Weser just as it empties into the North Sea, Langenbeck was l)orn November 8, 1810, in the small

village of Padingbiittel. His father, George Langenbeck, was the local clergyman and chaplain. His mother's maiden name was Johanna Sussmau. The father is said to have been a most excellent pastor, and teacher as well ; among his pupils was Count Borries. His half-brother, that is to say the halfuncle of young Langenbeck, was the well known Professor of Surgery at Gottingen, who was among the last of those who united the branches of ophthalmology and surgery.

Young Langenbeck early showed a great fondness for knowing how various animals "looked inside," and dissected these upon all occasions. He studied under the direction of his father, who designed him for the ministry, his studies being in part such as would pi-epare him for theology. What passed between father and son when the latter decided upon a different course is unknown. The fact in evidence remains that he entered the University of Gottingen, October 25, 1830, taking the medical course find remaining until 1834, Avhen he took for his graduating thesis a dissertation upon " The Structure of the Eetina." In this we may see the guiding hand of the uncle. That it was not due to this alone is probable, in view of the fact that a later addition was made to the thesis, concerning " Path. Anat. Alterations of the Ketina." Micro

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scojiical work thus early claimed his interest, and he was speedily made a Docent in physiology and microscopy. While continuing in this branch, he soon began teaching operative surgery on the cadaver, giving private instruction with great success.

(Soon after taking his degree, it is related that on returning for a visit to his father's house he was so besieged by the patients who Ciime to seek his skill that he had to get out of a window by means of a ladder in order to make his escape. At Gottingen his courses in operative surgery attracted so much attention that he thought it best to go away, out of consideration to the feelings of his uncle, the regular Professor of Surgery. He was speedily called to the chair of surgery at the University at Kiel. Not long after, one of the Holstein wars broke out and he entered eagerly upon the career of army surgeon.

His success upon the field was so brilliant that before the war was fairly over he was called to Beidin to fill the chair of surgery, left vacant by Dieffenbach, who fell dead in his clinic when about to operate. "Youth" and "book learning" were urged against his appointment, which was delayed for a time. When he finally came in 1848 he found a crowded auditorium and enthusiastic applause awaiting him on his first appearance.

Then came other Holstein wars, in all of which Langenbeck took part, teaching as well as operating throughout his service, resembling in this respect Larrey, for whom he had great admiration. Before coming to Berlin Langenbeck had every advantage of foreign study, visiting Paris and London. In the latter city he knew Sir Benjamin Brodie, Lawrence, and Henry Green. He was especially attracted to Sir Astley Cooper, who, retired from active work, was then living at his country seat. Having no children, he made sons of bis three nephews, the well-known surgeons Bransby Cooper, Aston Key, and John Tyrrel. Langenbeck was accustomed to meet them at their uncle's every Sunday, and passed delightful hours in their society. The pleasures and mutual advantage of social intei'course among jirofessional men as shown at the meetings of the London Medico-Chirurgical Society impressed him strongly, and during his entire after-life he was fond of gathering bis pupils about him. London was not revisited for forty-four years. During his thirty-four years in Berlin he founded the German Surgical Society, and for the last twelve years of his residence in that city was president of the Berlin Medical Society. When president of the German Surgical Congress he paid constant attention to every word of each speaker, although the long sittings must have been wearisome to him in his old age.

If Dioffenbach was the first great German surgeon, Langenbeck was the founder of German surgery as we know it to-day, where the constant striving is to build upon a foundation of biology and experimental pathology, where each result is subjected to the closest scientific scrutiny and criticism. He was a firm believer in carefully coiulucted experiments upon unimals to verify or disprove the value of new surgical procedures.

S I He was an enthusiastic army surgeon, participating in all the Holstein wars, in the war with Austria in '6G, and in the

Franco-Prussian war of '70. He took the most advanced ground in military surgery I'egarding the ambulance system, work on the field, and the absolute neutrality of hospitals. The Eed Cross movement excited his keen interest, and he attended the Geneva Conference, where decided advances were made. Any violation of the RedCross symbol to avoid capture excited his utmost indignation. He heartily endorsed the words of the German Emperor, who nobly said, "A wounded enemy is no more an enemy, but a comrade needing our help."

He endeavoi'ed to inspire his young army surgeons with the highest ideas of duty, saying, "While we may not expect a military surgeon to know everything, yet there are things he must know to a degree approaching perfection."

Nor did he fail to illustrate his stern ideas of duty, on the bloody field of Gravelotte, when, being told that his best beloved son had been fatally wounded, replied, " I cannot leave, my duty keeps me here." He did not see him until the day following. An English surgeon who accompanied the German army during the campaign of '70 was strongly impressed with the affection and reverence the young surgeons showed for Langenbeck. In this campaign he performed a large number of those subperiosteal resections with which his name will always be associated. He notes the greatly decreased mortality where a resection can be substituted for an amputation. Wherever there was much to be done he was to be found, although he never interfered with his subordinates nor deprived them of oj)erations which were his for the taking.

Langenbeck was a man who wrote but little when we consider the number of years he was at work. Thought and a conservative originality are on every page that came from his pen. His articles and pam^ihlets number but 47; his operations must reach into many thouands. He founded the Archiv fur Ohirurgie, and devised new methods of operating on hare-lip. His uranojylasltk, an operation for the closure of cleft palate in which the mucous membrane with the periosteum is loosened from the bone, is well known. Ilis joint resections are the best we have to-day. He was one of the earliest to advocate the immediate fixation of fractures by means of immovable dressings. Langenbeck reminds us that it was Heine who in 18.30-40 did the first subperiosteal resections, upon dogs. The results of his experiments are still to be seen in the iluseum of the University of Wiirzburg.

AVe must not forget to mention that while at Kiel Langenbeck was called to the chair of surgery at >[unich. The appointment failed of royal confirmation, and a favorite was installed in the place.

In his early days he was one of the first to assert that glanders was caused by a micro-orgiuiism. The real organism he mistook. The microscopes and the technique of that day did not admit of following up the ultimate cause.

Langenbeck w as the great teacher of surgery on the Continent. Pupils from distant partes of Europe and America fiocked to see and hear him. He was especially devoted to helping young men by every means in his power to acquire what they came for. Many of his pupils are now the most eminent surgeons of Germany ; among these may lie mentioned Billroth, Trendelenburg, Hiiter. Krouleiu and Rose. Billroth, Langenbeck's assistant for seven years, loved him as

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a father. He says, " His name is writteu in golden letters not only in the Book of History but in the Book of Love of all his pupils anil friends," and in speaking of his immediate popularity on assuming the chair of Surgery at Berlin, said, " In a short time he had conquered the hearts of pupils, colleagues and patients." "His charm of personality captivated all. lie was the inspired leader of youth, their incarnate ideal of a clinical teacher." " His place among us, or leather over us German surgeons, was at the same time by the grace of (iod and by our choice."

The occasion of his 70th birthday in Xovember, 1880, might be called a love-feast. Sixteen full professors of surgery who had been either his own assistants or those of his devoted followers, gathered about him, the students of the University gave him a torch-light procession, and the citizens in general taught the enthusiasm. Ilis was the wonderful gift of mingling freely with his subordinates without the slightest loss of their respect or admiration. Absolutely cold-blooded in operating, he was the kindest and most warm-hearted of men. To quote the words of another, " Endued with a sympathetic voice, he was at the same time fluent of speech and modest of demeanor, while he combined a charm and impressiveness of manner with an intimate knowledge of detail."

Small in stature and slight in figure, with an exquisitely refined face and a noble look in his eye, he was an aristocrat by nature and in feeling.

His life was an active one. He rose at five in the morning and took a horseback ride when the weather pei'mitted immeately after coffee. At six he gave a course in operative surgery on the cadaver to graduates in medicine or last-year students. At eight he saw his office patients. From ten to two he attended to his private practice and made his hospital visit. At two or soon after he operated daily in his clinic upon the most difficult cases. Finishing at 4.30 p. m., he spent the

remainder of the day with his friends, his family, or in writing.

He was an excellent teacher, clear in thought and expression, and careful in arrangement of his subject-matter. Langenbeck was a rapid and bold operator. He never failed to yeatly cover in the large defects left after removing extensive malignant growths from the face, bringing up and turning in flaps of skin from apparently impossible places, and seuding out the patient entirely presentable.

In operating he was fond of using small knives, which were sharpened in the operating room by the assistants immediately before an operation. When a knife had served him well in some imiiortant operation he was accustomed to have a small notch cut in the handle for future reference.

After an operation he invariably applied the dressing with his own hands. It was impossible not to give him your whole attention during a clinic or lecture. His earnest voice and fiery manner fascinated the beholder as if under the sjiell of a magician.

At the close of the Franco-Prussian war he was the recipient of honors and decorations from nearly every court of EurojJe, and the thanks of the Emj)eror, with whom he stood on the double footing of friend and physician.

Soon after his 70th birthday, with fame in no way diminished, he resigned his chair in the University on account of a cataract which interfered with his work. Eetiring to his beautiful villa situated on the hills overlooking the city of Wiesbaden, he passed the remainder of his days, dying September 29, 1887, of apoplexy, at the age of 77, leaving behind him a name which men delight to honor.

[I am under obligations to addresses by Billroth and Von Bergmann, as well as to an article in the London Lancet, for such facts as were not derived from my own knowledge of Von Langenbeck and his environment. — W. B. P.]

iTOTTsT I?,E.^X)"Z-.

VOLUME III THE JOHNS HOPKINS HOSPITAL REPORTS.

COPJTEISTS.

REPORT IN PATHOLOGY, II. Panillomatous Tumors of the Ovary. By .1. Whitridgk Williams, M. D. Tuoorculoslsot the Female Generative Organs. By J. Whitridoe Williams,

M.D.

REPORT IN PATHOLOGY, III. MultipleLympho-Sarcomata, wit ha report of Two Cases. By Simo.v Flexneb,

M. D. The Cerebellar Cortex of the Dog. By H enry .T. Beiiklev, M. D. .\ Case of Chronic Nephritis In « Cow. By W. T. Coi'.ncilm.\n. M. I). Bacteria In their Kolarion In Vegetable Tis.sue. By H. L. BnssELi,, I'll. D. Heart Hypertrophy. By W.m. T. Howahd, .Ir., .M. 1).

REPORT IN GYNECOLOGY, II. The 'iynecoloKlcal Operntinjr Room. .\n i;.xtiTrial Direct Method of .Measurini; the ConJUKata Vera. By Howard

A. Kei.i.v, M. D. rrola|)'<us Uteri ivlthout VcKlcal Diverticulum and with Anterior Enterocelo.

By HiiWAiiii A. Kelly, M. D Lipoma of the Ijiiiliiin Majus. By Howard A. Kelly, M D. Devlailoiisof the Ucetum and Blifmold Flexure associated with Constipation

a Source of Error in Oynecolojflcal Dlatrnosls. By Howard A. Kelly,

OporatlonB for the Suspension of the Retrolleicd Uterus. By Howard A. Kelly, M. D.

Nos. 1-3-3 (Keport In Patholony, III, $2.00; Nos. i-5-6 (Ueport In Patholony, III), cloth, fA.OO.

Subscriptlona may be tent to Thb Jouns UoPKiNa Phe89, Ualtiuobe, Md.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic

Cocci. By Mary Sherwood, M.D. Intestinal Worms as a Complication in Abdominal Surgery. By Albert L.

Stavely, M. D. Gynecological Operations not involving Coeliotoniy. By Howard A. Kelly,

M. D. Tabulated by A. L. Stavely, M. D. The Employment of an Artillcial Ketroposition of the Uterus in covering

Extensive Denuded Areas about the Pelvic Floor. By Howard A. Kelly,

M.D. Some Sources of Hemorrhage In Abdominal Pelvic Operations. By Howard

A. Kelly, M.D. Photography applied to Surgery. By A. S. Murrav. Traiinuitic Atresia of the Vagina with Htematokolpos and H lematometra.

By Howard A. Kelly, M. D. Urinalysis in Gynecology. By W. W. Kui5SBLL, M. D. The Importance of employing Aniesthesia in the Diagnosis of Intra-Pelvio

Gynecological Conditions. Demonstrated by an Analysis of !M0 Cases.

By IltiNTKK Koiiii, M. D. Uesuscitation in Chlorolorm .\siihvxia. Itv Howahd A. Kelly, M. D. One lliuidriil i 'uses or i ivariotoiny piTlnrm.'.l on Women over .'Seventy Years

of .\jfe. llv llOWAHI) .\. KlM.LV, M. I).. Mll.l .MaUV .'<IIKltWO()n, M. D.

Abdominal Oneralion.s performed in the (iyru'tol<>«ioal Department, from March 5, mm, to December 17, 18fe By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gj-necologlcal Department from June 6, 1890, to May i, 1892.

J3.00; Nos. 7-8-9 (Ueport In Gynecology, II), $3.00. Price of volume, bound in

May, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

65

A FATAL CASE OF PURPURA HiEMORRHAGICA, WITH EXTREME ANilMIA.

By John S. Billings, Jr., Assistant Resident Physician. [Read before the Hospital Medical Society, April 2, 1894.]

Tlie patient, a boy aged ten, was admitted to Ward F, March 22, 1894, comiilaiiiing of pallor and great loss of strength.

His family history was negative. No history of hemophilia. The personal history of the boy was very good. He had had the ordinary children's diseases, and had always been a strong and healthy boy.

Eight weeks before admission his mother noticed that he was becoming pale; also that he was languid and easily tired. She first noticed the spots on the legs about five weeks latei', but attributed them to bruises received while at play. This the boy denied. Two weeks before admission he began to have a slight cough, with blood-tinged expectoration. This has continued, and blood has been constantly present in the expectoration, though never in great amount.

No melfena, hsematemesis nor haematuria.

The bedside note on March 23 is as follows: "Extreme pallor of skin and mucous membranes. Sclerotics pearly. Pupils dilated. Eyelids a little puffy. Gums are firm and hard; no bleeding from them. There are two small ecchymoses on the inside of cheeks. No subcutaneous hemorrhages on face. On upper part of chest and at root of the neck there are a number of ecchymoses, chiefly deep-seated, ranging in size from a pin's head to 3 mm. in diameter. Over the right shoulder there is a larger extravasation like a bruise. Several ecchymoses and one or two suggillations on the back. There is a large subcutaneous hemorrhage over the right anterior superior iliac spine. Numerous hemorrhages, large and small, on the legs. No cedema of ankles.

Liver and Sjilecn. — No apparent enlargement of liver or spleen.

Lungs are clear on auscultation and percussion.

Heart. — ^Apex beat diffuse; most marked in fifth space, in nipple line. Loud systolic murmur at apex ; heard along anterior axillary fold, and very intense along left sternal margin. It is also heard in the cervical vessels.

Abdomen is negative; no tenderness; no arthritis; no enlargement of lymph glands."

Urine.— The urine showed a trace of albumen. No tube casts nor red blood corpuscles.

No blood in stools.

Twenty niinims of the tincture of the chloride of iron in sweetened lemonade, three times a day, were ordered. The boy bled very easily, a small prick in the ear continuing to bleed for an hour on one occasion.

The patient seemed to improve slightly for the first few days, but on the evening of March 30th the cough became more severe and the boy com[)lained of dyspntva and substernal oppression. The pulse became rapid and feeble, and death took place at 4 A. M. on the 31st. No autopsy was obtainable.

Blood. — The blood count on admission was as follows : Reds 090,000, wiiites 4000 per cmin. lla-moglobin 17 per cent. It showed a very severe graile of anaemia, the red corpuscles being only a little over one-tenth of (he normal number. The

haemoglobin was estimated by means of a Fleischl hsemoglobinometer, and the results are only of relative value, as the readings on this instrument are unreliable under 20 per cent. Daily blood counts were made until the day of death. The red corpuscles, as shown on the chart, ranged between 690,000 on admission and 483,000 on the 30th. There was apparently a slight rise on the 35th, but we must remember that we are dealing with relatively small differences. The limit of error with the Thoma-Zeiss hiemocytometer is, in our experience, between 100,000 and 150,000. Hence we must say that the number of red corpuscles remained practically constant. The hiemoglobin ranged relatively higher than the red corpuscles. This is not well shown on the chart.

Heated and stained specimens of the blood were examined ou March 23. There were only very slight variations from the normal in the red corpuscles, consisting chiefly in moderate differences in size. No poikilocytosis. No nucleated reds were seen. The amount of haemoglobin contained by the individual corpuscles seemed to be above normal. Many polychromatoijhilic red corpuscles were seen. Seventy-five per cent, of the leucocytes were of the small mononucleair variety. This includes the lymphocytes and small mononuclears of Ehrlich. No eosinophiles ; no adventitious forms.

Stained specimens were examined every other day, but showed nothing farther than an increase of the small mononuclear elements to 80 per cent.

On account of the subcutaneous hemorrhages, the anaemia and the hemorrhage from the bronchial mucous membrane, Dr. Osier is inclined to consider the case one of morbus maculosus Wcrlhofii. This is a form of purpura with hemorrhages from the mucous membranes occurring in infants, first described by Werlhof. The blood condition is most interesting and resembles closely a case reported by Ehrlich.* In this case, which was one of steadily progressive anaemia secondary to excessive menorrhagia, there was absence of nucleated red corpuscles from the blood, no leucocytosis, and a marked increase in the small mononuclear leucocytes. From observation of similar cases he draws the conclusion that when the 'oregoing conditions obtain there is entire absence of regeneration, and that the prognosis is distinctly unfavorable. The blood condition in these cases indicates that there is either no effort at regeneration on the part of the blood-making organs, or that there is some morbific influence at work destroying the corpuscles faster than they can be produced. In a case of fatal progressive ana^uia reported by Fischel and Adlerf the anemia was consecutive to a wound of the foot which suppurated. The blood showed all the features of a pernicious anaemia, and the post-mortem examination showed typical deposition of iron in the liver. Micro-org-anisms were found to be present in tlie blood two days before death. They were

• Charite-Aiinalen, XIII, 1SS8.

f Zeitsclirift f. Heilkumle, Vol. XXIV. Vart i.

06

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 40.

cocci and grew well on ordinary culture media. The authors claim to have produced a progressive fatal anaemia in animals by injections of cultures of this organism. No cultures were made in our case, but the history would seem to rule out anything of the sort. The absence of leucocytosis, the increase in mononuclear leucocytes, and the relatively high percentage of hitmoglobin are what one would expect to find in a case of progressive pernicious anaemia. The absence of large and

small nucleated red corpuscles and of poikilocytosis is, however, against it.

The absence of poikilocytotic changes in the red corpuscles is remarkable, considering the severe grade of the anaemia. It is probably to be explained by the relatively short duration of the patient's illness. In view of the recent work done by the Russian observers and others on the bone-marrow, it is unfortunate that no autopsy was obtainable.

BLOOD CHART.

BIOGRAPHY OF JOHN OF ARDERNE.*

By Thomas Windsor, Manchcsler, Enyland.

All that is really known is that he was born about 1308, f practised in Wiltshire ( VVilceshure and Wilteshure), M.S. f. 54, " hoc probavi in Vicecomite Wilteshure," and abroad (M.S. f. 49, "hoc probavi in uno Rege et doubus Episcopis in transmarinis partibus"), and afterwards at Newark, in Nottinghamshire, from 1.349 to 1370, :( when he removed to London, where be wrote his treatise on fistula in 1376, § and his " Cura oculorum " in 1377. ||

It has been supposed or asserted that he was educated at Montpellier and that he practised in France as a military surgeon <Haser : Lehrb. d. Gesch. d. Med.), that he practised at Antwerp (E. H. in his transl., Sloane, 2271), that he was at the battle of Crecy (E. Milward in a . . . letter . . . concerning . . . British physical & chyrurgical authors), and that he was surgeon to Richard II and Henry IV (W. Beckett in Philos. Trans. V. 30, p. 842).

I am not aware that any of these statements can be proved ; it may also be noted that he would be about 91 when Henry came to the throne. It may be mentioned that 3548 Sloane ends " explicit practica Henrici Ardern," and that in the Hunterian Library, Glasgow, there is a MS by Johannes Arderon " de judiciis urinarum," written apparently after the time of Henry the 4th.

I niiay just mention that the MSS. in the British Museum are almost invariably imperfect.

Contents of Manuscript of John Arderne's Works.

f. 41. Contra colicam et iliacam passionem. Modus ministrandi clysteria.

• In the ** Biojrraphy " as publish*^d in the March number of the Bulletin

several errors, duo to copying the manuscripi, appeared. These have been corrected by Mr. Thoma^i Wintlsor, and the memorandum is reprinted.

t Brit. Mus Sloane T.5, f^il. 146. After saying that his eyes bad become much weakened from study and writing up to the 70th year of his age, he says: " Et sciant preseutes & f uf uri cjuod Eko magister Johannes de Ardern chirurgioorum minimus hunc libelUmi propria manu mea exaravi apud london anno, viz., regui regis U'C. 2' primo et etatis meae Ixx.'*

X In most MSS. of his works : in one before me he says (f. 61. V; " Ego Johannes priedictus a prima pestilencia quae fuit anno dom. 1349 usque annum dom. 1370 moram traxi apud Newerk in Com. Nothing, (f. 63, r) Postea anno dom. 1370 veni London, et ibidem curavi . . ."

§ Sloane. 341. " Ego Joannes diet us Ardernecirurgicus scrips! hunc iibellum anno domino 1376 ad utiiitatem & conservacionein sanitatis humanie. ■viz. anno <luo princeps Edwardus princeps Walliie primogenitus Alius Edwardi regis migravit ad doniinum in die S. Triuitutis xi" idus Junii."

illst year of Richard II.

f. 43. Contra dolorem iumborum et renum. Contra lapidem in renibus.

f. 41. Contra ulcerationes vesica; vel renum.

f. 45. Confectio olei nardini. Regimen nefreticorum.

f. 46. Provocans vomitum

f. 47. Contra sanieni mingentes. Confectiaoleiamigda). Contra ardorem urina; et excoriationes virgoe inferius.

f. 48. Contra Shawedepisse (in other MSS Chaudepisse). Scolopendria.

f. 50. Contra lapidem.

f. 52. Contra inflammationes virgae vel vulvie.

f. 53. Contra ulcera sub prseputio.

f. 55. Contra inflationes testiculorum.

f. 57. Contra lacrimas & ruborem oculorum, etc. Modus purgandi.

f. 61. Cases of fistula ani.

f. 63. Behaviour of surgeon.

f. 67. Argentum vivum.

f. 68. Apostemata in ano.

f. 74. De restrictione sanguinis.

f. 76. Ung. Arabiciim. SIgnum perfectse curationis.

f. 81. Bubo est apostema infra anum in longaone. Various cases of fistula and other affections of the anus.

f. 8'). Pulvis grecus. Oleum rosarum. For to make oyle of roses (in English).

f . 86. To make a gode salve for a wounde (in French).

f. 87. Ad clarificandum visum.

f. 88. Confectio pulveris sine pare. Regula de crebra remocione plagarum.

f. 90. Plaga facta cum cultello vel sagitta.

f. 95. Repercussiva simplicia.

f. 97. Jlorsus canis rabid i.

f. 99. Contra emorroidas (gives a list of authors made use of).

f. 104. Cauterizantia.

f. 107. For the emorode.

f. 129. Curatio virgie inflatse & calidae cum rubore.

f. 130. Cura apostematum in genu.

f. 131. Cura apostematum in tibia.

f. 132. Quomodo cognoscitur caro mortua.

f. 133. Contra malum mortuum.

f. 136. Fistula &c. in digitis.

PROCEEDINGS OF SOCIETIES,

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of April 2(1, 1894. Dr. Kelly in the chair. An Interesting' Case of Trachoma.— Dr. Randolph.

This patient has just come into the hospital and I have brought him in this evening because I expect to operate to-morrow and remove the interesting oViJective features of the case. It is an advanced case of trachoma or gianular conjunctivitis. This disease is characterized objectively by the appearance in the conjunctiva of small granules ranging in size from a pin's head to a millet-seed and even larger. These granules attain a large size in the retrotarsal folds. The subjective symptoms are great pain and photophobia. Reganling the origin of trachoma, it seems to be now quite clear that it has a parasitic origin. Michel of Wiirzburg has done reliable work on this subject and has succeeded in getting out a micrococcus which is in some jioints like the gonococcus. Fuchs thinks that in its ultimate origin the disease is to be traced to an infection from the genit.-vls. There is a difference between the

disease as met with in this country and in Europe. It is highly infectious as seen in Europe. I have never been able to satisfy myself as to its infectiousness in this countrj-. It is no uncommon thing in Europe for whole households to be affected. The treatment is to excise the granules and the folds, and it is interesting to note the fact that this is one of the most ancient methotis of treating the disease. For a long time this method fell into disuse and was never adopted. It is now, however, in cases like this one the main method of treatment.

Exhibition of Dcrinatoloarical Cases. — Dr. Gilchrist.

Dr. Gilchrist exhibited a patient, a colored woman, having an interesting papnlo-squamous syphilitic eruption simulating psoriasis very closely. He exhibited also a case of (vsoriasis by way of contrast. Sections were exhibited under the microscope illustrating the lesions in both diseases. One of the sections was from a case of psoriasis where one of the lesions was situated on a scar which is perhaps the lirst case of the kind on record. This section illustrated the comparison between the- normal skin, the normal scar and the psoriasis on the scar.

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[No. 40.

A Fatal Case of Purpura Haeiiiorrhagica, with Extreme AniPinia. — Dr. Billings. (See page 05.)

Dr. Th.wer. — I have very little to add to what Dr. Billings has said. It was an extremely interesting case. He lost very little blood while in the hospital. The amount he coughed up was not enough to account for tlie rapidly progressing anaemia. The only thing that could possibly account for the manner in which he failed was the entire absence of effort on the part of the blood-forming tissues toward regeneration. It corresponds to the class of cases which Ehrlich spoke of years ago, and is similar to a case which he recorded in 1884 of a young woman having a very severe postpartum hemorrhage, after which the blood showed conditions not unlike this. The patient went steadily down and died in the course of a week.

Dr. Osler. — This is the .second instance of this form of purpura hsemorrhagica which we have had in the hospital. One case recovered. It was severe enough to be termed purpura h?emorrbagica, as the patient had hemorrhage from nearly all the mucous membranes. We have liad one fatal case of hiemophilia in a man belonging to a bleeder family.

Dr. Thayer. — In the first case referred to by Dr. Osier there was an immediate leucocytosis after the hemorrhage, and an immediate appearance in both cases of nucleated red corpuscles. In the man who died of hsemophilia, within 48 hours after the time the hemorrhage began, there were well-marked changes in the marrow of the bones.

Papillomata of the Ovary. — Db. Cullen. (To appear in June Bulletin.) ,

Db. Kelly.— Cystic papillomata of the ovary are comparatively common, and I think the reason a greater number of cases have not. appeared in medical literature is that after a subject has been investigated and written up to a certain extent, there is a general tendency among writers to neglect it and to branch off into newer fields.

This subject received considerable attention among gynecologists about twelve years ago, but since then little of value has been added until Dr. Williams presented his excellent monograph as a result of his laboratory work and bibliographic research.

A considerable number of these cases have come under my observation and they are always interesting.

If the papillomatous process has not involved the peritoneum it can be completely eradicated by enucleating the diseased ovary, hut if the disease has spread from the ovary to the atljacent structures only a palliative operation can be done.

The early clinical history of these cases is not suggestive of the true nature of the disease.

Unless there is a large tumor which ruptures and in that way diseeminates its papillary elements throughout the peritoneal cavity, one is not apt to recognize that papilloma is present, although the patient may have been complaining for a long time.

A case which I saw in my office to-day aptly illustrates this statement. The patient, who had been complaining more or less for three or four years, was first referred to me for examination by Dr. Salzer two years ago. At that lime I was unable to discover any pelvic lesion. Since then the patient has gradually declined in health, and as she again began to suspect that the pelvic organs were at fault she was referred to me for the second time. My examination to-day revealed papillomatous masses in the pelvis.

I recall another patient who had fallen into ill health ; the disease at first i>rosented the Bymi>toms of dyspepsia, but finally assumed a typhoidal character. As the attending physician could discover no cause for the patient's continued ill health, and wishing

to eliminate the pelvic organs as a possible seat of her disease, called me in consultation.

A vaginal examination revealed a papillomatous mass involving the ovary and extending to the adjacent i)eritoneum. Operation was refused at that time. Two months later, after ascitic fluid had begun to accumulate, the patient was subjected to coeliotomy. A large papillomatous mass was enucleated, and although there still remained suspicious flake-like patches attached to the intestines, it was hoped that all of the diseased structures had been removed. The patient recovered from the operation, but died suddenly ten days later of a coronary embolus.

In all cases where the patient is declining in health without apparent cause, presenting ill-defined dyspeptic symptoms, or slight fullness of the abdomen suggesting a beginning ascites, a careful examination of the pelvic organs should be made.

If these cases are subjected to operation before the papillomatous process has extended beyond the affected ovary, a perfect recovery may be expected.

Dk. Welch.— This tumor is quite different from an ordinary cystoma of the ovary. Many years ago it was generally supposed that these papillomatous cysts of the ovary were nothing but ordinary cystomata which had growths on the inside and on the outside of the cyst walls. They are now known to be a distinct type of tumor of the ovary. As a rule, these cystic papillomatous tumors have nothing to do with cy.stomata. A cystoma of the size of these tumors would be made up of a number of small cysts. A cystoma, again, would have thick, viscid contents, whereas here the contents of two of the cysts were thin and watery. I believe these tumors belong to that class which Dr. Williams has demonstrated as springing from the germinal epithelium of the ovary. It is interesting that the same abnormal growth into papillomata has taken place on the surface of the ovary as on the inside of these cysts. I should be inclined to regard these cysts as developed from the Graafian follicles.

Dr. Kelly. — Dr. Welch will perhaps remember a very small papillomatous growth, about the size of a pea, springing from an ovary of normal size, which I removed about two years ago. In this case the diseased ovary was discovered during an operation for retroflexion. The patient has recovered completely and shows no signs of a return of the growth. I would like to ask Dr. Welch if the impression which prevailed some years ago, that monocystic tumors of the ovary are peculiarly prone to become papillomatous, is true.

Dr. Welch. — That is true.

NOTICE.

All inquiries concerning the admission of free, part pay, or private patients to the Johns Hopkins Hosjiital should be addressed to Dr. Henry M. Hurd, the Superintendent, at the Hospital.

Letters of inquiry can be sent, which will receive prompt answer, or personal interviews may be held.

Under the directions of the founder of the Hospital the free beds are reserved for the sick poor of Baltimore and its suburbs and for accident cases from Baltimore and the State of Maryland. To other indigent patients a uniform rate of to.OO per week has been established. The Superintendent has authority to modif)' these terms to meet the necessity of urgent cases.

The Hospital is designed for cases of acute disease. Cases of chronic d;sease are not admitted except temporarily. Private patients can be received irrespective of residence. The rates in the private wards are governed by the locality of rooms and range from 115.00 to f.SS.OO per week. The extras are laundry expenses, massage, the services of an exclusive nurse, the services of a throat, eye, ear and skin or nervous specialit-t, and surgical fees. Wherever room exists in the private wards and the condition of the patient does not forbid it, companions can be accommodated at the rate of $15.00 per week.

7%« John* llopkint llonpital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimore, from whom single copies may be obtained; they may also be procured from Messrs. GUSHINO <£ CO. and the BALTIMORE NEWS COMPANY. Subscription, tl.OO a year, may be addressed to THE JOHNS HOPKINS PRESS, BALTIMORE ; single copies will be sent by mail for fifteen cents earh.

BULLETIN

OF

THE JOHNS HOPKINS HOSPITAL.

Vol. v.- No. 41.]

BALTIMORE, JUNE-JULY, 1894.

+++

Contents

The Significance of Albuminuric Retinitis in Pregnancy. By Myoma complicating Pregnancy and preventing Delivery.

Robert L. Randolph, M. D., 69 Porro-Ca'sarian Operation modified by dropping the Pedicle

An Operating Table. By Hunter Robb, M. D., - - 73 ' [Dr. Kelly] ;— Infusion of Normal Saline Solution in conPrimary Carcinoma of the Gall-Bladder. By Delano Ames, nection with Gynecological Operations and the Accidental

M.D., ^^1 Hemorrhage of Parturition [Dr. Kelly]; — Exhibition of

Proceedings of Societies : Surgical Cases [Dr. Finney] ; — The Lesions caused by cer Hospital Medical Society, 80 | tain so-called Toxalbumins [Dr. Flexner].

THE SIGNIFICANCE OF ALBUMINURIC RETINITIS IN PREGNANCY.

AN ANALYSIS OF FIVE CASES, WITH THE HISTOLOGICAL CHANGES PRESENT IN' THE RETINA

IN ONE CASE.

By Robert L. Randolph, M. D.

Two 3'ears ago I had my attention called to the importance of this subject by a case seen in consultation with Professor Kelly of the Johns Hopkins Hospital.

Case I. — Mrs. N., 31 years old ; 3 children living, and up to the 4th month of her 3d pregnancy had enjoyed good health. In the early part of the 5th month of her 3d pregnancy she began to have violent headaches, which were almost constant, and they could only be relieved by strong anodynes. These headaches persisted for two weeks, when she noticed that her sight was growing dim. Her sight continued getting worse till it had reached a stage when, from her own account, she was practically blind in one eye and the sight in the other eye was but little better. At this time an oculist was called in, who pronounced it albuminuric retinitis and suggested an examination of the urine. This was done, and the urine was found to be rich in albumen, and casts were also found. The induction of premature labor was advised and performed, and the child was born dead. The woman had convulsions, but recovered, and in a few months was in comparatively good health again. Her sight was gradually but completely restored. One year later she again conceived, and about the 4th month of [ircgnancy was attacked with similar headaches, tliough they were not quite so violent in character. Fearing that her sight would become involved, she consulted an oculist, who, from the complete description he gave of the ophthalmoscopic condition, must have made a very painstaking examination. He came to the conclusion that she was suffering with tlie degenerative form of allniniinuric retinitis, and that if she waited for normal labor slie would unquestionably lose her sight and probably her life. Her family physician then sent

her to Dr. Kelly, that he might induce premature labor, giving as the main reason the condition of the eyes and the prognosis held out by the oculist. The case was referred to me by Dr. Kelly for examination. I found that her vision was ;? in both eyes, and that there was present in both eyes a low grade of hyperopic astigmatism. As to the condition of the fundi, I found absolutely nothing to denote a progressive disease. The fundi presented all over a granular stippling, with here and there the faintest suggestions of pigmentary deposits, such a condition as is not infrequently found associated with high degrees of myopic astigmatism. The question was whether or not to induce premature labor. I may add that she had a faint trace of albumen in her urine, but no casts. There was then, in my opinion, not the slightest suggestion of albuminuric retinitis, and had she not gone nearly blind at a previous pregnancy the question of inducing premature labor would never have arisen. From my examination, then, I concluded that the evidence did not justify the induction of premature labor. I saw no signs of a progressive retinitis, and viewing the condition of the retinte exactly as they were, and entirely uninfluenced by the previous history, I told Dr. Kelly that, so far as her eyes were concerned, I saw as yet no reason for bringing on labor. My advice was followed and the patient sent home. A few months later her family physician wrote Dr. Kelly that she had given birth to a boy and had gone through an easy labor.

Ca$e II.— Mrs. W., 26 years old. Married 11 months. Two months after seeing Case 1 I was called to see a case in consultation with Dr. T. H .West, of Keyser, W. Va.. who fold me the woman had been complaining of dimness of vision and violent headaches, but he

70

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had not laij any special stress on the latter symptom, thinking it was due simply to indigestion incident upon her condition. She was in tlie oth month of pregnancy. I found that with one eye she could count fingers across the room, but could not see ♦© read ; with the other eye she could read ordinary print. I had no test types with me and hence could not ascertain her actual vision. I found with the ophthalmoscope that the fundus in both eyes was covered with soft white patches. These white patches were nearly confluent in the worse eye, so that the fundus looked perfectly white. The patient had been in bed for nearly two weeks, as her nose would bleed every time she sat up or moved about. This nose-bleeding, then, was the only evidence of ill-health present, and until I gave my opinion as to the condition of the retime her physician had not thought of any serious disease. Iler urine was immediately examined and found loaded with albumen ; casts were also found. There was every reason to believe that the retinitis was progressing, and inasmuch as she had nearly four months before confinement, I felt justified in advising her physician to bring on labor. I was confident that the retina would be permanently destroyed if pregnancy were allowed to continue to full term. Dr. West induced premature labor, and the latter was easy, and a dead child was born. Her sight was gradually restored, and though I never had an opportunity of making an examination, I learned that a few months after her confinement she could see as well as ever. Her health continued delicate, and her urine was never free from albumen. Three months ago Dr. West told me that she was again in the 7th month of pregnancy and that her sight was becoming affected. She was very anxious for a child, and fearing that her physician would bring on labor, as he had done before, she had delayed revealing her conditiom Her symptoms alarmed her and she sent for Dr. West late in the 7th month. At this time she had some local dropsies, very noticeable about the labia majora. The urine was rich in albumen, and her sight growing worse every day. I advised premature labor at once, and expressed some doubt whether sight would be saved, as she had undoubtedly gone too long. Her labor was an easy one and the child lived three days. Since Saturday, April 14th (Dr. West wf ites me), she can no longer see a person across the room.

C«»c III.— A. H. (colored), 26 years old. Has three children. Married five years. One miscarriage. Just before birth of second chilli she noticed dimness of sight. This disappeared, and her attention was not attracted to her eyes till she was four months advanceil in her 3d pregnancy. Her eight grew worse every day, and all this time she suffered with the most violent and persistent headaches. Her child was born, and four months afterwards she came to the Dispensary of this Hospital. The following was the condition of her eyes : R. E. V=z ;Vu ; L- E. V= j^",, . Both fundi were beset with large white plaques. In the right eye there were some opacities in the vitreous, and the optic nerve was pale. The white .spots were confluent in the macula region, forming a solid white background. I found a similar condition, somewhat less marked, in the left eye, the o])tic nerve in this eye not being involved. The diagnosis of albuminuric retinitis was readily made. I examined the urine and found a quantity of albumen, and also casts. She was referred to the medical side of the Dispensary. She died very suddenly a few weeks later, and I succeeded in getting one of the eyes, which I hardened in Midler's fluid and studied the histological changes.

Case IV.— Mrs. S., 32 years old. Has two children. When 1 first saw her she had just recovered from her 2d pregnancy, when she said she had nearly lost the sight of her left eye, and the other eye was also affected. I found evidence of retinitis in the left eye. There were very minute white specks with pigmented borders collected in the macula region, also some spots of pigment in the same locality. Her vision in this eye was ;^ In the other eye, vision was U- I prescribed glasses for her (I may add she had a slight grade of hyperopic aslig., and had come to me for headaches), and

lost sight of her for 18 months, when she returned with the request from her family physician. Dr. Gombel of this city, that I examine her eyes. She was in the 4th month of pregnancy, and fearing that she would lose her sight if she went on to full term, her physician sent her to me and told her that he would induce premature labor if I thought her eyesight was in danger. She was very poor, and I soon found out that neither she nor her husband wished for more children and were exceedingly anxious for a legitimate excuse for getting rid of the fcetus. I examined her eyes most carefully and found no difference in the condition from that seen some months before. There was no change in either the subjective or objective condition, and I did not think that this justified the immediate induction of labor, and so wrote to Dr. Gombel, who refused to bring on labor. She was determined, however, to have her pregnancy terminated, and four weeks later. Dr. Gombel tells me, he was called in and found her moribund with peritonitis. She had sent for a midwife, who had produced abortion that resulted in her death.

Case V. — Mrs. R., 40 years old. Has had eleven children, and is now in the 5th month of her 12th pregnancy. Ten days ago noticed that the sight in her left eye was very dim, and that she did not see as well as usual witli her other eye. She had been troubled with a great deal of what she called " neuralgia of the head." This condition grew rapidly worse, especially in the left eye, the right eye remaining unchanged. When seen at the Dispensary of the Johns Hopkins Hospital she looked pale and waxy, and I elicited the fact that her feet were somewhat edematous. Her vision in the left eye was reduced to counting fingers in three feet, and in the right eye vision was jg. Ophthalmoscopic examination showed large white patches around the optic nerve in the left eye. The entire retina looked pale, and the outlines of the disc were blurred. No noteworthy changes in tlie blood-vessels. There were several small patches in the macula region. The right eye showed three small white plaques near the optic nerve ; further than this, nothing abnormal. I diagnosed the condition albuminuric retinitis, and had an examination made of her urine. This was found to contain slightly over j%'^, albumen, and granular casts were also present. There was then no doubt about the gravity of her condition, and I advised tlie induction of premature labor as the only means through which she could regain her sight. I have not seen her since, but have learned that both she and her husband concluded to have nothing done and to wait and see " if nature would not bring things all right." I shall inquire into the case four months hence.

AVhat were the prominent syniptonis that characterized the liistories of these five patients ? In the first three and last casi' the dimness of sight and lieadaches. In these cases there was not the slightest suggestion of kidney trouble outside of the ocular complication, and it was this latter condition that alarmed the attending physician and finally led to the discovery of more imporant and far graver conditions. It is clear then that much weight sliould be attached to dimness of sight occurring at any time during pregnancy.

In looking over the literature of this subject one will be disposed to divide the albuminuric retinitis of pregnancy into two classes: 1st, those cases where the eye symptoms appear before the Oth month ; 2d, those cases where the eye symptoms appear later than the 7th month. I should place cases I, II, III and V in the first class, and case IV in the second class.

Retinitis alhumiiiurica in its relation to pregnancy is certainly worthy of more than a passing notice, and yet in the majority of obstetrical works there is no special warning to

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the physician to heed all symptoms of visual disturbance, nor is even the special gravity of the condition mentioned. It is surprising to see how much has been written in this connection by ophthalmologists in the past ten years, and how in every case reported what serious conditions were present. From remarks let drop to me in talking over the cases with others, I am led to think that at least one case of eclampsia falls to the lot of most practitioners, and I think that were it possible to get the complete history of the pregnancy of eclampsia cases, in a large number eye symptoms more or less pronounced were present at some time during pregnancy, and generally in the earlier months, and it is just at this point, when the eye symptoms manifest themselves, that a serious view of the case should be taken. In the cases reported by other observers the physician in charge became alarmed at the first suggestion of eye trouble, and had an ophthalmoscopic examination made at once. It should be remembered that failing sight is often the first indication that the woman's health is failing, and is the first symptom to which she calls the doctor's attention. The retinal lesion is often the index of the systemic condition, and the slightest disturbance in sight may mean just such a lesion ; and while other signs, such as large quantities of albumen in the urine, the presence of granular and hyaline casts, and wdema of the feet, are probably indispensable for a diagnosis of nephritis, these latter conditions will almost certainly be found in the pregnant woman whenever the ojahthalmoscope reveals the changes in the retina known as albuminuric retinitis. But even the absence of the more obvious signs of nephritis should not lead us to underrate the significance of the retinitis, for Howe reports a case where both retinaj in ilay presented the typical picture of albumiiiuric retinitis, and where an examination of the urine during the course of four months failed to reveal albumen, and it was not till September that albumen was found, and then in considerable amount; a fact which, I think, enhances the importance of an ophthalmoscopic examination. In Case I, vision was nearly extinguished at a previous labor. As a general thing, after such an experience, the family physician warns his patient against the dangers of becoming pregnant again, as the history of most cases goes to show that with every succeeding pregnancy greater inroads are made upon the integrity of the retina. The 1st and -Ith cases reported would seem to show, though, that it is quite possible for a woman who has been nearly lilind from renal retinitis at labor to go through her next pregnancy without the slightest return of the eye trouble. When such cases as cases I and IV present themselves to the oculist for an opinion, unless there be evidences of an existing disease in the retina, the question of premature labor from the ocular point of view is not to be considered. Such a case should of course be returned to the obstetrician, who will be guided by other signs.

I followed this course in cases I and IV, and subsequent I'vents verified my oi)inion. On the other hand, as regards ' ases II, III and V, there was not the slightest doubt in my mind that unless pregnancy were terminated at once blindness would follow. A retina that was so evidently diseased in its entirety would surely be destroyed if the conditions that

gave rise to this disease were allowed to remain three or four months longer. Howe's statistics in these cases, when labor was not induced, show that when the woman escaped with her life it was only to remain blind forever afterward.

In those cases where the retinal trouble manifests itself in the last seven weeks of pregnancy we may give a more favorable pi-oguosis, and unless the retinal lesion be very pronounced and the quantity of albumen great, hesitate before advising the induction of premature labor. The later the renal retinitis makes its appearance the more favorable the prognosis as regards sight, and when showing itself in the last two weeks of pregnancy, recovery of sight follows almost invariably.

1. Visual disturbances occurring in the first six months of pregnancy, and especially when associated with violent headaches, frequently mean albuminuric retinitis, and if this condition is found, to save sight, pregnancy should be at once terminated.

2. Visual disturbances showing themselves in the last seven weeks of pregnancy, while indicating the same retinal lesion, are of less grave import in so far as sight is concerned, and unless these disturbances are very pronounced and associated with wide-spread ophthalmoscopic changes, should not in themselves call for the induction of premature labor, for here their history goes to show that sight is completely restored after labor. This is especially true when the retinitis shows itself in the last two weeks of pregnancy.

3. The occurrence of renal i-etinitis in one pregnancy does not mean that the woman will be likewise affected in a subsequent pregnancy, and even though headaches be present and albumen found in the urine, so long as the fundi are free from the usual signs of an existing albuminuric retinitis the question of sight should not properly be considered.

Pathology.

Denissenko denies the existence of an Mnflammatory exudation, and regards the retinal changes as merely cedematous, and proposes to substitute the name of ophthalmia Brightica or oedematosa, for that of albuminuric retinitis. Holsti, who has investigated the subject, says that the affection comes from intlammation of the coats of the arteries, and that the walls arc changed into a shining homogeneous mass resembling colloid degeneration. Jlaguire holds that the changes are degenerative in character and due to excessive intravascular tension, and that this alone will cause the hemorrhages and nutritive disturbances. Weeks thinks that the alterations are of a fibroid or hyaline nature taking place in the blood-vessels.

Duke Charles Theodore of Bavaria found that arteritis was verv common in the retinal siffections of Bright's disease, and that the chief changes are in the capillary layer of the choroid and in the retina, and more in the former. The coats of the larger vessels in the retina present a waxy structure; in other parts are homogeneous. Small aneurisms may be present and hemorrhages into the sheath of the vessel. The inflammatory process is specially well marked in the capillary area between small arteries and veins. There is thickening of the vessels associated with degeneration of ret! and white blood corpuscles

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and by cedematous swelling of the walls. The lumina are sometimes narrowed, and thromboses occur. There is an infiltration of the rods and cones by small cells, and the formation of hyaline masses in the granular layers. He did not find traces of sclerosis of nerve fibres. The arteritis is seen in vessels of the sclerotic, ciliary body, iris and conjunctiva.

Diffuse opacity of the retina is mainly due, says Sauudby, to cedema, the lymph spaces around the ganglion cells of the nerve-fibre layer being distended with a clear fluid, so that these drop out of the section, leaving large spaces. AA'e may have an effusion of coagulable lymph in the outer molecular layer, or such an exudation may separate the membrana limitans externa and bases of Miiller's fibres from the rest of the nerve-fibre layer, while the layer of rods and cones may show great thickening. Small angular spots of pigment appearing in the periphery are of less importance, and are due to changes in the pigment epithelium. Sometimes, says Saundby, choroidal hemorrhages may occur, giving rise to atrophy of the choroid at this spot and pigmentary disturbance. Hemorrhages, the same author wiutes, occur in the sheaths of the retinal vessels. Interstitial neuritis is sometimes seen with round cell infiltration of the connective tissue of the nerve, leading in some cases to atrophy of the nerve. Ivanoff found a serous transudation into the retina in the immediate vicinity of the blood-vessels, and thinks that the outer' coat of the vessels and not the inner coat is affected.

Pathological Histology in Case III.

As regards the optic nerve itself, I think we may safely say it was normal. There might have been increased nucleation in the papilla, noticeable in and about the perivascular spaces. The main point of interest here was a beautiful endarteritis of the central artery, not amounting to obliteration, but to a considerable narrowing of the lumen of the vessel. One saw here what some authors speak of as fibrous thickening of the intima. The central vein was engorged with red blood corpuscles, a condition peculiar to the veins everywhere throughout the sections and in every part of the eye. The choroid was normal with the exception of the condition of the veins just mentioned. In the retina marked <ind interesting changes were present. The layer of rods and cones was absent in places, a loss due. doubtless, to meclianical violence in the preparation of the specimen. The membrana limitans externa was possibly somewhat thickened, and had a wavy course due to the pressure from the swollen inner layers. The external granular layer was increased in depth and the cells were pressed apart. Further than this there was an absence of any histological change in this situation. The external molecular layer showed marked changes — Ist. The fibres of Midler were swollen and pressed apart, and in some places there were large spaces, the latter being filled with disintegrated blood corpuscles, hyaline masses, and sometimes distinct fibrillated fibrin. The walls of these spaces were lined with very fine drops of hyaline material. Fibrin in no inconsid.erable amount was also present generally in that ])art of the layer >)etween the spaces. Some of the smaller spaces were blocked up with hyaline masses. Here and there were small hemorrhages. At some i)oint8 the spaces were so large as to invade the external granular layer. The internal granular layer presented, in the main, changes similar to those in the external molecular layer, except that there was an absence of the spaces seen in the latter. The internal molecular layer, ganglion-cell layer, and nerveflbre layer presented noteworthy changes. At points there was an enormous increase in the neuroglia (sclerosis), and this was

especially marked in the nerve-fibre layer. The fibres in this layer were swollen and somewhat translucent. This sclerosis was more pronounced in certain spots ; spots no doubt corresi)onding to the location of the white patches seen with the ophthalmoscope. These spots of sclerosis appeared like nodes, involving all the layers of the retina down as far as the internal granular layer and almost destroying the identity of the layers as such. The nervefibre layer was thickened throughout, and minute hemorrhages were visible. The ganglion-cell layer presented peculiar changes. Adjacent to and within the nodes the cells were frequently absent, having dropped out of the section, leaving vacuoles. When present, some of them were much enlarged, some were smaller than normal, others without processes. With eosin-hfematoxylin stain some of them presented a brownish red and rather singular color. The relatively great size attained by the ganglion-cells is, according to Weeks, brought about by imbibition, a part of the general cedema. Small hemorrhages and hyaline drops were present in the internal molecular layer.

The principal features then were :

1st. Great oedema of the entire retina, and as a consequence increased depth of the retina.

2d. Hyperplasia of the neuroglia, especially marked in the nervefibre layer.

3d. The presence of hyaline masses throughout the retina, most pronounced in external molecular layer and the formation of spaces.

4th. As a general thing the changes were more striking the nearer the disc, and this was especially true of the nodule.*!, which here were very prominent, though they were visible along the retina almost as far forward as the ora serrata. The anterior portion of the eye was normal. Fatty degeneration of Miiller's fibres observed by Leber and Duke Charles Theodore was not seen in this case, though the failure to find this condition does not disprove its existence. Miiller's fluid was employed in hardening the eye, and this could account for the failure to detect the changes described by Leber and others, and in like manner postmortem changes may be held responsible.

As to the frequency of sclerosis of the neuroglia in albuminuric retinitis, I am disposed to regard it as of exceptional j occurrence — if ever present at all — when pregnancy alone j not associated with genuine interstitial nephritis is the cause | of the albuminuria. It is frequently difficult to ascertain the i subsequent history of this class of patients, but whenever the eyes have been tested some mouths after premature labor, in most cases useful vision was present, and there was good reason to believe that vision would still further improve. In some few cases nearly normal vision has been reported. Anything like restoration of function in a part the subject of sclerosis is certainly not in accord with our ideas of this process, as witness for example the prognosis of the same condition when present in the cerebro-spinal system, in which latter connection Flint says, "Clinical experience thus far has furnished no ground for entertaining any hope of recovery from the disease." The blindness, then, which is present in albuminuric retinitis is due to a-dema of "the retina, and consequent interference with the conductivity of the nerve-fibres. This (edema may be in many cases a part of the general anlema familiar to us all, an oedema which usually disappears with the removal of the fretus. The sclerosis found in Case III leads me to conclude that the nephritis at the last was not of the parenchymatous variety, as are most of the cases of nephritis of pregnancy. The disappearance, however, of the visual disturbances and headaches at the termination of her

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Fig. 1. — Modified Operating Tabk for AbJoruinal Section.

Fig. 2.— Modified Table for Plastic Operation.

Fig. 3. — Modified Operating Table, Trendelenburg Position.

June-July, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

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second preguaucy speaks in favor of a purencbymatons nephritis in the early part of her history; a nephritis that in exceptional cases, as in this one, passes over into the interstitial variety ; a condition that we no doubt had here, as evidenced by her sudden death, and by the clinical history of the retinitis, as well as its histological changes.

IjITERATURE.

Abortion for the Albumiuuric Retinitis of Pregnancy. By Lucien Howe, M. D. Amer. Jour. Ophthal., 1886, No. 2.

All)uminuric Retinitis during Pregnancy. By Theodore Mii.Kwell, M. D. The Lancet, 1878, Vol. 2, p. 900.

Ein Fall von Retinitis albuminurica mit hochgradige Netzhautablosung wahrend der Schwangerschaft entstanden. Von H. Buch in Berlin. Archivf. Ophth., 2. Abth., 102-114.

The Prognosis as to Life in Renal Retinitis. By Simon Snell. Trans. OpTi. Soc. of United Kingdom, Vol. VII, 1888.

Another Case of Albuminuric Retinitis of Pregnancy. By A. B. Williams, M. D. St. Louis Med. and Surg. Jour., 1887.

.Albuminuric Retinitis. Its Dangers and Diagnosis. By A. D. Williams, M. D. St. Louis Med. and Surg. Jour., 1887.

Retinitis Albuminurica during Pregnancy. Premature Labor with Improvement of Vision. By W. O. Moore, M. D. The Planet, 1883-84, I.

Albuminuric Retinitis without Albumen. By Lucien Howe, M. D. Trans, of M. Society, State N. Y., 1893.

Graviditut in 8. Monat. Beiderseitige Retinitis albuminurica mit Netzhautablosung. Von Dr. Hester. Chariti-Annalen, 2. Jabrgang.

Retinitis Albuminurica. Improvement after Premature Labor. By €. Macnamara. The Lancet, 1878, Vol. 2, p. 842.

Retinitis Albuminurica and Pregnancy. By Frank Van Fleet, M. D. N. r. Med. Jour., Sept. 2G, 1871.

All)uminuric Retinitis. By A. Emrys-.Tones, M. D. British Med. Jour., April 14, 1883.

Two Cases of Severe Albuminuric Retinitis coming on during Pregnancy. Recovery of health and good sight in both eyes after miscarriage in one and artificial premature labor in other. Oph. Hosp. Reporl.i, Vol. II, 1886-88.

The Middlemore Lectures on Retinal Affections of Bright's Disease and Diabetes. By Robert Saundby, M. D., F. R. C. P. Birmingham Med. Review, Jan. 1893.

A Contribution' to the Pathology of Albuminuric Retinitis. By Dr. John E. Weeks of N. Y. Archives of Ophth., Vol. XVII, pp. 276-291.

Zur path. Anat. des Auges. By Duke Charles Theodore. Wiesl)aden, 1887.

The Changes in the Eye in Bright's Disease. By G. Denissenko. Med. Westnik. 1882, Nos. 49 and 50, and 1883, Nos. 2 and 11.

Ueber die Veriinderungen der feinen Arterien bei der granuliiren Nierenatropbie und deren Bedeutung fiir die pathologischen Krankbeiten. Von H. Holsti. Deutsch. Archiv fiir klin. Med., XXXVIII, p. 122.

Traite des Maladies des Yeux. IvanofE (A.). Conf. Wecker, t. II, p. 316.

By Hunter Robb, M. D., Associate in Gynecology. \^Read before the Johns Hopkins Hospiial Medical Society, May 21, 1894.]

I have recently had made an operating table which is a modification of the one devised Ijy Dr. Kelly, which you have all seen in his operating" room. It is made of quartered oak and is 80.5 cm. high. The top, which when complete measures 110 cm. by 51..5 cm., is constructed in three separate pieces, which, for convenience, I will call A, B and C. The middle portion, B, measuring 1.5 cm., is made like an extra leaf of a table to slip in and out, so that when required the table can be at once shortened by joining A and C, so that the top consists only of these two parts. This allows the ansesthetizer to administer the ansesthetic during an operation on the cervix or perineum with the patient in the lithotomy position, without leaning forward in a constrained position, as he is obliged to do when the ordinary table is employed (Figs. 1 and 2). The part 0, again, consists of two pieces which are joined together ljy hinges. The part which works on these hinges can at iiny time be elevated at any angle and kept in the required position by means of a wooden support 11 cm. wide and IS.Ti cm. long, one end of wliich is attached to the table on its under surface by a double hinge, while the other can be fitted into a series of grooves in a plank which lies a little below and parallel to the top of the I able. In this way we have a simple apparatus when we wish to employ the Trendelenburg position (Fig. 3). The legs of the patient when in this position rest upon a support which is attached to the elevated portion of the table at a convenient

angle. Instead of being made in one piece, the middle portion of this support, which is 30 cm. long and 30 cm. wide, is constructed to fit into grooves in the two projecting side-pieces, so that when it is no longer required it can easily be removed. This is necessary, because if left in place it would obstruct the lowering of the table when a horizontal surface is required.

The support for the feet of the patient, when undergoing an abdominal operation, can be used as a seat for the operator when lie is engaged in plastic work. In the two pieces of wood which connect the seat with the table, holes are drilled which are intended to receive two pegs, the tops of which are represented by two triangular pieces of wood. When in position they can be used to support a glass basin, which thus rests just in front and within easy reach of the operator, and into which can be put the scissors, knives and any instruments which are constantly being required during a plastic operation. This seat, as well as that for the an»sthetizer, ca\x be put out of sight, being suspended under the table at any time when not in use. The legs of the table at one end are supplied with rubber casters, so that the position of the table can bo I'eadily changed.

A wooden box is fastened on the under surface at the side of the table near the head, in which are kept the anesthetic, cones, hypodermic syringe and other things that may be required during the operation by the ana?sthetizer.

The advantages which the table possesses are as follows :

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(1) it is inexpensive ; (2) it can be readily sterilized ; (3) it can be shortened at a moment's notice; (4) the patient can easily be placed in the Trendelenburg position at any time, even in the middle of the operation, without being removed from the table; (5) the seats for the operator and the anaes

thetizer, when not required, are out of the way ; ((5) a convenient receptacle for some of the most necessary instruments is put within easy reach of the operator; (7) a box is supplied to hold the ether, chloroform and cones ; (8) the table can readily be wheeled from place to place.

PRIMARY CARCINOMA OF THE GALL-BLADDER.

By Delano Ames, M. D. [Read before the Johns Ilopkim lloipUal Medical Society, May 21, 1894.]

About one year ago the first case that I shall report this evening came into my care through the kindness of Prof. Osier, to whom I am also indebted for the histories of the two other cases reported, which occurred iu this hospital.

Case I. — Primary carcinoma of the gall-bladder. Pain and tum,or in the right hypochondrium. Absence of jaundice. Profound anmmia. Obstinate constipation for four weeks before death. Death from exhaustion six days after exploratory incision. Oall-atones.

Miss R. H., aged 47, was in my care from May 5, 1893, to Jan. 15, 1894. She had been an invalid for some years. Her mother is said to have died from some painful liver trouble. Her previous health had never been of the best. Since childhood there is a history of attacks of pain in the right side, occurring with' increasing frequency as she grew older. She never was jaundiced during these attacks and never passed calculi. She ivlw.ays menstruated regularly, never freely, and for the last few years has sufferoil more or less pain in the left inguinal region during the menstrual i)eriod. Two years ago, during a severe attack of pain in the right side, she first noticed a slight swelling just below the right costal margin in the mammary line. This subsided with the pain. The duration of these attacks was from six to eighteen hours.

Aside from this trouble, and with the exception of a troublesome cough, for which she sought the climate of southern Europe two winters ago, she had been free from disease.

Her appetite was only fair at all times. Her bowels moved from 2 to .3 times a day.

On my first visit. May 5th, I made the following note : " Patient is fairly well nourished. Complexion sallow. No jadndice. Conjunctivce are colorless. Mucous membranes of mouth are very pale. Ears waxy. Pulse 84, volume and tension good.

Thorax: — Fairly well developed. There is a small amount of subcutaneous fat. Expansion good, but apparently slightly restricted at left apex, where the expiration is somewhat prolonged. No r&ies are to be heard. Heart negative.

Abdomen: — Soft. Walls are thin. Just below the right costal margin the surface is a little elevated in a small area in the mammary line. Tliere is tenderness here to slight pressure, and she tells me that yesterday when the pain was more acute this elevation wtis more marked. Liver dullness begins at the 0th rib. The border is palpable about two fingers-breadth below the costal margin and is painful to piessure. The surface is smooth and firm. The left lobe is not palpable." The urine examined a few days later was free from albumen and casts, but showed slight traces of biliary coloring matter. Htemoglobin was not estimated at this time, but three months later, after the patient liad been in the country all summer, it was between 28 and 30 per cent.

A few days later the slight elevation noted on my first visit was found to be much accentuated and to be extremely sensitive to pressure. The patient was having a severe attack of pain in the right side.

Dr. Osier saw the case at this time and believed it to be probably one of chololithiasis of long standing, with adhesions of the gallbladder to surrounding parts ; the recurring attacks of swelling and pain in the region of the gall-bladder being referable to intermittent obstruction of the cystic duct. Operative interference was not advised on account of the patient's anaemic condition.

From September until December the patient's condition remained practically stationary, but from the latter date she began rapidly to grow worse, having several severe attacks of pain in the former place within a short time. During one of these attacks her temperature rose to 101°, but quickly subsided. After the attack the liver border was found to be somewhat lower than on the first examination. With the pain, as with all previous and all subsequent attacks, there was a slight menstrual flow and pain in the left inguinal region. This latter pain always accompanied defecation, and was increased if the stools were loose or the action constipated.

Although from this time the patient grew steadily worse, her appetite improved and there was no noticeable emaciation. Another marked change occurred ; instead of having from 2 to 3 stools a day she suddenly and without apparent cause became obstinately constipated.

An examination made the middle of December showed the liver border palpable on a line with the umbilicus. The left lobe was still not palpable. There had thus been a noticeable descent of the right liver border in a short time.

On Christmas day occurred the most severe attack of pain yet experienced. The whole right hypochondrium was distinctly bulged ; the liver border was 1 to 2 fingers-breadth below the umbilicus, and beneath it could be felt a rounded mass, which by bimanual palpation, one hand in the (lank and one over the liver border, could be slightly moved up and down. It was not possible to make out any fluctuation. There was great tenderness, not only at the liver border, but over the whole liver surface. Twelve hours later the bulging was much less perceptible, the pain had gone, though some tenderness remained and the liver border was again on a level with the umbilicus.

Within eight days a second similar attack occurred, at which time it was decided that operative interference was advisable, as all the symptoms pointed to a probable occlusion of the cystic duct. An incision was therefore made by Dr. Tiffany on .January 9th. The gall-bladder was found to be the scat of a cancerous growth and to be firmly adherent to surrounding parts. The patient died six days later from exhaustion.

The autopsy was made the following day at the bedside, and as we were not allowed to remove the organs, the report is far from being as full as would be desired.

The gallbladder was enlarged to about the size of a large orange. It was dark brown in color ; its walls were much thickened and the seat of a carcinomatous growth. On section, its cavity, which was small, contained a little brownish fluid, mushy detritus, and what was of most interest, the disintegrated remains of several gall

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stones. The mass was adherent to the duodenum for several inches below the stomach. It was also adherent to the under surface of the liver, and had, as it had grown, drawn down a tongue like process of liver tissue in the way recently describeil by Riedel.

The liver, so far as could be seen, was free from secondary deposits, though it is very probable that a closer examination would have disclosed some metastatic nodules, as invasion of the liver in these cases is very common.

There was no constriction of the intestines. The lumen of the duodenum was normal. No growth was found at the pylorus or in the pancreas. The left ovary was cystic, about the size of a walnut and adherent to the rectum. This fact probably explains the pain in the left inguinal region referred to.

Case II. — Cancer of the gall-bladder. Jaundice. Progressive emaciation.

E. S., aged 54, female, admitted to ward G, January 25, 1893, complaining of pain in the abdomen and of soreness in the back. There is nothing of moment in the family history. She has been married, has had six children and four miscarriages. Has never had uterine trouble, and no serious illness until the present attack.

More than a year ago she had quite severe pains in the back accompanied with high-colored urine. After several of these attacks she passed small calculi in the urine. She has had none of these attacks and has passed no stones for about a year. For the past few months she has been failing in health, has had indigestion, belching, and occasional attacks of vomiting. She has lost much weight. About five weeks ago she noticed that she was growing yellow, and for about the same' length of time she has had a dull aching pain in the right side of the abdomen. Tlie urine has been high-colored, and the stools, formerly dark in color, have been light gray.

Present condition : — Patient is a medium-sized woman, face is thin, but the body and limbs are still well nourished. There is a moderate jaundice. Abdomen is full. On palpation it is soft, nowhere painful except at a point 5 cm. below the costal margin in the nipple line. Here is a firm mass which extends to the left to within 6 cm. of the umbilicus, and at this border the fingers can be placed directly beneath it. Below it reaches to the transverse navel line, and is here rounded and the finger cannot be placed beneath it so well. To the right the margins are not very clearly defined, but the mass extends nearly to the tip of the ICth rib. Above it cannot be separated from the liver. It feels like a rounded mass the size of a lemon or a little larger, is extremely resistant, hard, and though it has the situation of the gall-bladder, scarcely conveys the impression of the rounded pear-shai)ed outline of that organ. The right kidney cannot be felt. The mass, though directly continuous with the liver, presents a flat tympany on percussion. Deep pressure from behind in the flank presses the mass forward.

The spleen is not enlarged, stomach not dilated, the pelvis is clear. The urine is dark-colored and there are a few granular casts. The stools are clay-colored and very offensive. Repeated examinations showed essential changes in the condition of the tumor mass. The jaundice became very much more intense, though the general symptoms were somewhat ameliorated. She took her food better and had much less pain. The case was regarded as tumor of the gall-bladder associated with gall-stones and probably malignant disease. The patient's condition was so satisfactory that it was thought advisable to have an exploratory operation to determine the exact nature of the trouble. Therefore, on February 8th Dr. Halsted made an exploratory incision. The mass described was in the position already referred to between the transverse colon and the under surface of the liver, to which it was firmly adherent. The adhesions to the colon were so tight it was thought inadvisable to attempt to separate them. The tumor mass waa firm, solid, and grayish white in color ; it passed beneath the surface of the liver and occupied the position of the gall-bladder. The

liver itself was not enlarged, but the edge could readily be felt about 6 cm. above the lower border of the tumor mass.

The wound healed, but the jaundice persisted and she got progressively emaciated. Her friends took her home on March 2, where she subsequently died.

Cask III. — Persistent jaundice with emaciation and ascites. Nodular tumor at the edge of the right liter lobe.

Magdelen H., aged 52, admitted to ward G, October 18, 1892, complaining of swelling of the abdomen and legs.

Her father died of tuberculosis. No history of cancerous disease in the family.

The patient has always been a very healthy woman ; was married at 22 and has had one child. Has been troubled for many years with constipation. She has never had attacks of colic.

The present illness, dating from the middle of June, began with vomiting, after which she became yellow and had an itching of the skin. The jaundice has never entirely disappeared. The legs became swollen about the end of August, and the abdomen six weeks ago. There has been pain in the back so that she always has to lie on the side ; otherwise she has not much distress. The stools have been yellow. She has had but little vomiting. There has been progressive loss of flesh and strength.

Present condition : — The patient is much emaciated and has an intense olive-green jaundice. There is general anasarca. The abdomen is extremely distended and the lower zone of the thorax is expanded. Without going into details foreign to the main point, it may be said that she had all the signs of obstructive jaundice and an ascites which required frequent tapping. The immediate interest in the case was in the condition of the liver. After tapping, this was distinctly palpable, and in the parasternal line the rounded edge could be clearly felt about two fingers-breadth from the costal margin. Passing towards the flank in the anterior axillary line a prominent nodular mass was reached, and here the liver border was nearly 7 cm. below the costal margin. The mass felt about the size of a walnut, was prominent, not umbilicated. No other masses could be felt, but the edge of the liver in the parasternal line was somewhat irregular.

Autopsy : — This showed a primary carcinoma of the gall-bladder, the end of which was the nodular mass which was so definitely felt on palpation. The walls were greatly thickened and the bladder contained about 100 small stones. There was great induration about the common duct, the head of the pancreas and in the gastrohepatic omentum. The common duct passed through this mass and was almost occluded. The liver weighed only 1500 grammes, and presented numerous medium-sized cancerous nodules throughout its substance. '

In all these cases, but especially in the first and third, it was difficult to make au exact diagnosis from the symptoms and signs. In Case I, although all the symptoms pointed to trouble about the gall-bladder, there was no jaundice, and though malignant disciise was thought of, the diagnosis of cancer was not made because of the absence of cachexia and emaciation. One point in favor of the diiignosis of cancer was the profound and obstinate auivmia, the hemoglobin never registering above 38 to 30 per cent. The case was regarded as one of long-standing cholelithiasis until the operation showed the presence of a neoplasm.

The chief points of interest about the cjise were: the rapidity with which the unfavorable symptoms develoj^ed: the rapid apparent increase in the size of the right loin? of the liver while the left remained normal: the intermittent swellings in the right hypochoudrium : the absence of jaundice, cachexia iind emaciation; the presence at autopsy of apparently di.^integrating gall-stones.

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In Case III the persistent jaundice and loss of weight suggested a new growth, but whether in the stomach, in the pancreas or in the liver, it was almost impossible to say. A test breakfast showed free hydrochloric acid, and she had not much vomiting since admission to the hospital. The stools were grayish yellow, not fatty, and not suggestive of pancreatic disease. The nodular body at the right border of the liver was the main objective point in the examination, and the question was discussed — before the class — as to whether this was a secondary growth, or the projecting end of a firm, hard cancerous gall-bladder. Supposing it to be secondary cancer of the liver, the organ was not nearly so enlarged as is common in this condition at the end of five or six months. On the other hand, in primary cancer of the gall-passages the liver is not so enlarged, and the jaundice, as in this case, is intense from the outset. A point in favor of this view was the absence of evident signs of disease of the stomach, pancreas and intestines.*

At the best, carcinoma of the gall-bladder is not very easy to recognize, but in doubtful cases there ai-e certain points with regard to sex, age, and the previous history of the patient that sometimes will assist us in making a diagnosis.

Historical.

The literature of primary carcinoma of the gall-bladder is all of comparatively recent date; the most important contributions having been made within the last five years. By far the largest number of cases have been reported since 1870. To-day cases are constantly appearing, especially in the clinics of large hospitals, and we are beginning to regard as not uncommon a disease that has hitherto been considered rare. There is reason to believe, however, as Kanvier and Fagge have- pointed out, that a number of these cases are still overlooked, especially when there are large cancerous deposits in the liver, such being too hastily regarded as primary in that organ.

Previous to the year 1800, 1 have been able to find records of but four cases of primary cancer of the gall-bladder. Two of these are mentioned by Stoll in 1777; one by Halle in 1786, and one by Baillie in 1794. All of these are included in the series collected in 1890 by Courvoisier.

During the first half of the present century but nine cases were reported, two of which were probably secondary to cancerous growths elsewhere.

The first two of these were reported in 1839 by Heyfelder, and during the same year Cruveilhier in his Pathological Anatomy mentioned the disease in speaking of the pathology of the gall-bladder, but did not go into any detailed description of the lesion.

The first full account of a case was given in 1840, by Durand-Fardel. In this the liver was not involved. Lasaze, in 1847, published a case in which also the liver was free from secondary deposits, and was not involved by continuity of growth from the gall-bladder, the most frequent way in which the disease involves neighboring parts. During the same year Notta published an account of a case.

•Oaler, Wm. Lectures on Abdominal Tumors. 1894.

In 1848, Broca, and in 1849, Rippoll, each reported a case to the Anatomical Society of Paris.

The two cases that were probably secondary were that of Burridge in 1845, which is included as primary by Courvoisier, but excluded by Musser, because of cancer of the breast of some years standing, and that of Kenaud in 1848.

During the next decade (18.50-1860) nine cases were reported, and the literature was enriched by a number of valuable contributions. Heschl in 1853 reported a case, and refers to two others that he had seen, both of which were associated with chololithiasis. leery and Mahieux, in 1853, each published a case. During the remaining years of this decade articles appeared, and cases were reported by Klobe, Topinard, Lebert, Pepper, Cassignac and Markham, the latter describing a remarkable case in a young woman of 28.

From 1860-1870 fifteen cases were reported. Wagner in 1863, Gull in 1864, Cornil, Foot and Stokes in 1865,- reported cases, though that of the latter was probably secondary. Frarier, Lutton and Buchereau in 1866, Moxon and Paulicki in 1867, Calmetts, Murchison and Ogle in 1868, Klebs and Willigk in 1869, also reported cases.

Since 1870, the French, hitherto the chief workers in the field, have given place to the Germans, and scarcely a year has passed but some additional contribution has been made to the subject.

During 1870, Villard published the most complete paper that had as yet appeared. He was able to collect and analyze 36 cases.

Important articles have appeared at different times, in Germany, by Kohn, Kraus, Lang-Heinrich and Zenker, who reported 8 new cases and collected 28; by Bernheim and Stiller, who added 5 new cases to the list, and by Courvoisier, who devoted a chapter of his " Pathologic und Chirurgie der Gallenwege" to a summary and discussion of 103 cases.

In England, Fagge, Moxon, Habershon, and Moore have been the chief contributors, while in this country a most interesting and important paper was published in 1889, by Musser, in which he analyzes 100 cases and gives a brief synopsis of each.

Of late years the greatest interest has attached to cases of primary carcinoma of the gall-bladder, because of the association of gall-stone with a large percentage of such cases. Two views of the relation of chololithiasis to the cancer formation are held, which will be briefly discussed in another paragraph.

Symptoms.

The most important symptoms of the disease are: jaundice, presence of a tumor, pain, emaciation, vomiting and nausea, ascites, constipation or diarrho?a, loss of appetite and progressively increasing weakness.

Hemorrhages into the various tissues of the body may occur; hiccough, ptyalism and dysentery have been noted in a few cases.

Jaundice is present in a very large percentage of cases (69). It may be very slight, or progressively increasing in intensity. In a certain number it is absent. When present, it is due either to a new growth in the ducts, or occlusion of the same by stones, inflammation, or pressure from without by enlarged

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glands. The skin may only present small pigmented areas, associated with more or less pronounced itching.

A tumor mass is noted very frequently. Its most frequent position 'is in the right hypochondrium, though it may be found occupying the area of the pylorus, or lie as low as the inguinal region. In one case it was noted in the right iliac fossa and diagnosed an ovarian cyst, the mistake being discovered upon operation.

The mass is composed either of the much enlarged gallbladder, or more frequently of the gall-bladder and a portion of the liver attached to it.

The size may vary greatly. In some instances the whole right hypochondrium is noted as bulged, as in the first case reported this evening. The tumor may be solid or fluctuating, and at times is so movable as to have been mistaken for movable kidney.

Pain, when present, is generally comjjlained of in the region of the liver. In the larger number of cases it is paroxysmal and lancinating in character ; the paroxysms varying in duration from a few minutes to some hours. It is frequently preceded by a sensation of weight and discomfort in the right side, and is often accompanied by darting jjains in the right shoulder and arm. At times it is colicky in character and complained of in the epigastric region. In certain cases the pain increases in severity and the attacks in frequency as the disease advances. Tenderness to pressure over the tumor mass is usually present, and during the attacks of pain is accentuated.

Emaciation is not as frequent a symptom as might be expected. Musser finds it in 49 cases, but considers it probably more prevalent. In a case reported by Wagner and in the first case reported this evening, the flesh was preserved.

Vomiting or nausea is present in about one half of all cases. It is occasionally obstinate and distressing. Bloody vomit has been noted.

Ascites is occasionally present and is usually accompanied by oedema of the lower extremities.

Constipation or diarrhcea is frequently noted. They occasionally alternate. In one of the cases reported constipation set in suddenly, without apparent cause, four weeks before death. Previous to this the patient had three stools a day, with a tendency to more.

Loss of appetite, usually accompanied by symptoms of indigestion and progressively increasing weakness, frequently occurs.

Hemorrhages are noted by Musser as occurring in a few cases. In two of those that I have collected they are noted; in one, into the peritoneum and body cavity ; in the other, into the mucous membrane of the tongue and into the skin of the abdomen.

Fever, which is rarely noted, is never high. It usually accompanies the paroxysms of pain. I have found records of one case in which the temperature was subnormal nuist of the time.

With regard to sex we find, as we would naturally expect, knowing that chololithiasis is most freqiient with women, that the largest percentage of cases of primary carcinoma of the gall-bladder occur among women.

In Courvoisier's cases there were four females to one male. Musser found that it occurred in the ratio of three females to one male ; while the ratio 4: 1 occurs in the cases that I have collected.

There is no more satisfactory explanation for the occurrence of cancer of this kind in .3 to 5 times as many women as men than there is for the more frequent appearance of chololithiasis in the female sex.

A study of the ages at which the disease is first noticed shows that it is distinctly one of middle and advanced life, or to be more accurate, of the otb, 0th and 7th decades. By far the largest number of cases occur between 50 and CO. In Musser's table, 29 are recorded in this decade, and in Courvoisier's, 26 as against 20, the next greatest in any decade, which occurred between 60 and 70. The number gradually rises from the first decade to the sixth, and declines to the ninth. The youngest reported occurred at 4 years, in a boy, following a fall. One is reported by Markham, in a girl of 28, and one by Schubert, in a man of 28. In ilussers table, one between 80 and 90 years is I'ecorded, and in Courvoiser's, two.

In the cases that I have collected : one occurred between 20-30 ; none between .30-40 ; six between 40-.50 ; nine between 50-60; four between 60-70; five between 70-80.

The dui'ation is stated by Professor Stiller in his conclusions, drawn from the five cases that he had studied, to be between five to six years. This is distinctly at variance with the views held by other authors.

Courvoisier states that the disease is one of months, not years, and tabulates his cases as follows :

Duration 1-2 weeks, 3 cases ; 3-7 weeks, 14 cases ; 2-3 months, 9 cases ; 3-4 mouths, 10 cases ; 4-5 months, 3 cases ; 5 months, 5 cases; 6 months, 7 cases; 7 months, 1 case; 8 months, 1 case; and summarizes, 36 of less than 4 months duration, 2 of longer than 6 months, the average being barely 3 months. Musser, on the other hand, assigns 6s months as the average duration of the disease.

These differences of opinion can only be reconciled on the view that the different observers dated the beginning of the trouble from the appearance of different signs and svmptoms.

It would seem impossible to assign any definite date for the beginning of the morbid process with aTiything like accuracy, because the various symptoms are known to appear at times during the progress of the disease widely different in different cases. All that we can say with confidence is that from the appearance of the symptoms the disease is one of short duration, the carcinoma developing with great rapidity.

Pathology.

As carcinoma of the gall-bladder is usually not discovered until so far advanced that such noticeable symptoms as jaundice, emaciation and pain have set in. we rarely have au opportunity to study this condition in the early stages in those who may have died from some intercurrent disease.

In such cases as come to autopsy, the gall-bladder is found to be converted in part or as a whole into a cancerous mass, usually adherent to surrounding parts, especially to the liver, duodenum and hepatic flexure of the colon. The mass is either round or pear-shaped, and in all cases where not eon

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siderably dilated appears to be solid. It usually varies in size from a little above normal dimensions to as large as a child's head ; tlie larger tumors being generally due to dilatation. It is whitish or brownish in color, has in general ;; firm, more or less elastic consistency when scirrhous in character, and is more soft and juicy when fungoid. As a general rule the surface is smooth, but at times it is found studded here and there Avith small nodules, which, according to Klebs, are secondary deposits in the overlying peritoneum.

On cutting into the mass there is found at about its center either the obliterated remains of the gall-bladder, or else its much contracted cavity, usually partly filled with a brownish fluid, sometimes purulent, and containing gall-stones or the fragments of former calculi.

The small-sized tumors are rarely made out on physical examination, while the larger ones are found either projecting below the liver border or imbedded apparently within the substance of the liver, depending, probablv, ou the original position of the growth ; or again they are found lying under a tongue-like process of liver tissue which they have drawn down with them as they grew.

The primary position of the carcinoma may be either at the fundus or at the neck of the bladder. The position was only mentioned in twelve of Musser's cases, and occurred six times in each locality. On the other hand, Courvoisier believes that the fundus is more often the starting-point, and suggests as a reason the more constant irritation from gall-stones that would be likely to occur here.

The cancer spreads either by forming metastases in distant parts, or by continuity of growth into neighboring organs.

One form of growth by continuity is described by Courvoisier, where the neoplasm invades such distant organs as the ■ stomach, jmncreas, etc., by growing across adhesions, using them, so to speak, as bridges.

Distant organs are comparatively rarely involved by metastatic growth. The liver, however, is frequently involved in this way, the secondary deposits being generally found on or near the surface of the organ. Growth by continuity most frequently involves the liver, forming at times masses of cancerous growth much larger than the original growth in the gall-bladder. In these cases Naunyn believes that the primary growth reaches the liver probably through the bile passages (Reichert and Du Bois Raymond, Archiv, 1866, H. No. 6). Klebs suggests, on the other hand, that these may have become secondarily involved from growth in the parenchyma which has become cancerous through growth by continuity. He inclines, however, to Naunyn's view.

Willigk has reported a very interesting case in which the growth extended tree-like into the liver substance about the bile-ducts.

In most cases the growth in the gall-bladder is scirrhous in character, the walls being transformed in part or as a whole into a dense, coarse fibrous tissue, generally poor in cells, in which epithelial cells are found arranged either in solid clumps, isolated or confluent, or as alveoli and sometimes resembling the acini of glauds, which may be either straight or branched. Occasionally the cells are found lying in long single rows between the fibers of connective tissue. The

neoplasm is believed by many to develop either from the epithelial layer of the mucous membrane or from the glandular tissue in the mucosa. The cells are either round or cuboidal, and rarely a flat-celled growth is met with. In a number of cases in which the gall-bladder is dilated, papillary growths are found u^ion its inner walls that consist of solid tongues of epithelial cells, which on section may be seen running as deeply into the bladder-walls as through the muscular coat, where they often take on a glandular arrangement.

Frequently the mucous membrane is found absent in places or entirely wanting. The walls are occasionally ulcerated ; where this has gone far enough, fistulous openings are formed frequently into the duodenum or transverse colon. There is in these cases generally an involvement of the intestine in the cancerous degeneration. Murchison states that of several cases of such fistula which he saw, the gall-bladder was cancerous in all but one. Degenerations occasionally occur in the cancer mass, and calcareous nodules are sometimes found.

A few pathologists, among them Forster, believe that carcinoma of the gall-bladder is in most cases secondary to a growth in the liver. This view is probably incorrect, because, as Klebs and others have pointed out, the gall-bladder is found to be uninvolved in most cases of primary liver cancer.

As to the liver itself in these cases, it is most frequently enlarged. Of the other cases, about half are atrophic ami half of normal size. In a very few cases abscesses are found.

The U'elation of Chololithiasis to Pkimakv Caroi NOMA OF THE GaLL-BlADDER.

Two directly opposite views are held respecting the relation of gall-stone formation to cancerous growth in the gall-bladder. According to such men as Klebs, Von (Schupple, Murchison, Durand-Fardel, Krauss, Zenker and others, the new growth may be directly attributed to the prolonged irritation produced by gall-stones, especially in persons predisposed to cancer. Zenker holds that an adenoma develops by irritation, and that it changes into an adeno-carcinonia, which is the primary atypical growth. On the other hand, Lutton, Lancereaux, Lang-IIeinrich, Forster and others hold that the presence of the neoplasm favors the formation of calculi, and is the cause, not the result, of gall-stone formation. It is a well recognized fact that biliary concretions are found in a very large percentage of cases of carcinoma of the gall-bladder.

In Courvoisier's list, the percentage in which stones were actually found was 91 per cent. There is good reason to believe, however, that these figures should be larger, as in a number of cases in which calculi Mere not found there were such evidences as scars and strictures of the ducts to show the former existence of chololithiasis.

In Musser's cases the percentage was 92 per cent., while in those that I have collected stones were found in 30, were noted as absent in 1, and were not mentioned one way or the other in 7, making the percentage of cases with, to those without concretions, 95.4 per cent.

These figures are too great to allow us for an instant to suppose that the association of these two conditions is mei'ely accidental. The most important point to be settled, and the

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one which it seems would be conclusive, is whether the formation of gall-stones precedes or follows the cancerous degeneration.

Evidence in favor of the former view is plentiful, while that to support the latter is very meager, though there are a number of theoretical considerations used as ai-guments that it will lead us too far to discuss here.

I have been able to find but one case, i. e. that of Ord, cited by Musser, in which a calculus existed which was definitely proved to be post-cancerous in its formation, and this stone was not a cholesterin formatiou, but consisted of phosphate and carbonate of lime with altered mucus. On the other hand, there are numerous observations that go to prove the existence of stones prior to the carcinoroatous growth.

In one of Zenker's cases, for example, fragments of calculi were found, and in the first case I have reported this evening the calculi were much disintegrated, which would seem to point to a degeneration, not to a formation of gall-stones. This fact, in connection with the long-standing history of biliary colic, is conclusive, and would lead us to believe that in all cases when there has been a previous history of biliary colic, and when no stones are found at autopsy, they have existed, but have undergone some such disintegration before the death of the patient.

Again, in one of the cases reported by Klobe an old stone was found with commencing cancer of the neck of the bladder. Klobe states it as his belief that the small size of the gall-bladder in many cases of cancer would be against the formatiou of calculi, while Zenker holds that the growth in the bladder and ducts would tend to prevent the bile entering the bladder, and so prevent the formation of stones.

Quetsch reported a case in which stones had been passed by a biliary cutaneous fistula for 3 years prior to any signs of cancer ; and cases are reported in which stones were found although the cystic duct was occluded; they have also been found buried in the mass of the neoi^lasm.

From all these facts it would seem that if we are justified in ascribing a causative influence to local ii'ritation in case of cancer in other situations, we should look upon gall-stones as exerting the same influence in these cases.

Finally, in closing, we may briefly summarize the most important points, following closely the conclusions reached by Dr. Musser, as follows :

1. Primary carcinoma of the gall-bladder is much less uncommon than was formerly believed.

2. It occurs most freijuently in women, the ratio being 3-5 : 1.

3. It is a disease more jiarticularlv of the middle decade of life.

4. Gall-stones are found in from 91-95 per cent, of the cases, and probably bear a causative relation to the disease.

5. Metastasis is not extensive: invasion of neighboring organs by continuity, common.

6. Adhesions to adjacent organs frequently occur. Ulceration and perforation are more rare.

7. Pain, jaundice, cachexia, emaciation, tumor, indigestion, nausea, vomiting, constipation or diarrhani, with occasional ascites and cedema, are the chief symptoms.

8. Pain occurs in 62 per cent. (Musser).

9. Jaundice occurs in 69 per cent. (Musser.)

10. Tumor occurs in 68 per cent. (Musser.)

11. The disease is always fatal, and usually in a short time, the average duration varying according to the best authorities from 3 to Gl months.

12. Death is due to exhaustion, peritonitis, metastasis to other organs, and to biliary obstruction.

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Dublin Q. J. Med. Sc, 1861. XXXI, p. 2aS-240. Belgodere, A.: Sur les Tumeurs formees par la Vesicule Biliaire. Montpellier,

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der Gallenblase. Dissert., Greifswald, 1890. Charcot: Maladies des Vieillards. Charpentier: Presse Med. Beige, 1876, T. 28, p. 89. Chiari, H.: Gallertcarcinom der Gallenblase nebst Cholelithiasis. Ber. d. k. k.

Krankenanst. Rudolph-Stiftung in Wien (1879), 1880. p. 484. Chouppe : Bull. Soc. Anat., 1872, p. 282. Collinet : Bull. Soc. Anat., July 1 and 15, 1892. Coraza: Schmidt's Jahrbficher, 1873, Bd. 160. Cornil and Charcot : Mem. de r.\oad. do Med.. T. XXVII. p. 349. Cornil and Ranvier: Manuel d'Histologie Pathologique, T. II. Corraza : Bull. Soc. Sled, di Bologna, Serie 5a, T. 12, 1871, p. 133. Corvisart : Bull. Soc. Anat., 1S48, p. 43. Cossy : Bull. Soc. Anat., 1878, LIII, p. 462. Coupland. S.: Primary Cancer of the Gall-bladder. Tr. Path. Soc. Lend., 1879-80.

XXXI, p. 136-138. Cruveilhier: Traitfi d'Anat. Path. Gen., n, pp. 542 and 543. Courvoisier: Kasuistische-statistische BeitrSge zur Pathologic und Chirurgle

der Gallenwege. Leipzig, ISSKI. Cowy : ProgrOs Med. Paris, 1879, VII, p. 205. Delageniere : De la Cholicj'stenterostomie. These, Paris, 1890. Dcnuce: Tunieui-s et Caloules de la ViSsicule Biliaire. These. Agpeg. Paris,

1886. De Vincentis: Resoc. Acad. Med. Chir. de NapoU, 187S, XXXII, p. lOT-IiO. Dupr4, E.: Des Infections Biliaires. £tude bact^riologique ct cUnlque.

These, Paris. 1890. . Durand-Fardcl : Bull. Soc. Anat., 1S38, XIII, p. I,i7-160. Eustache : Jour. Med. Sc. de Lille, March 20, l&H, annc. 7. Xo. 6. Fagge : Guy's Hosp. Reiwrts. 1875, XX, 3rd scries, p. 167. Fazio, F.: Giorn. Internaz. d. Sc. .Med.. 9, 1887. p. 385-397.

Foot, A.: Cancer of the Gall-bladder. Dub. Q. J. M. Sc., 1SS5. XXXIX, p. 218. FOrster: Path. .Vnat., II, p. 206. Frarier; Bull. Soc. Anat., 18<i6, p. .'>6-o9. Frerichs: Tralttf pratique des Maladies du Foie. p. 661. Funcclus: Uebor Gallensteinen und ihre Folgcn. Dissert., Bonn, 187S. Gcrstang: Lancet, ISSS. II, p. 963. Goodhart : Atlas of Illust. Path. Syd. Soc. Pub., ISSS. Gull: Lancets London, 1864, 1, p. 699. Haas: Pragcr Vtel. J- Schrift, Ber. ilb. med. Klinik. v. Jakscb, 1874-75, Bd.

132, p. I;M-137. Habershon: British Medical Journal, 1872. Habcrsbon : Some Diseases of the Liver. Philadelphia, 1S7S. HaWf : Hist, de la Soc. de Med., 178*1 (Paris. ITW). p. 1».

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Kiinot et Oilbei-t : £tudes sur les Maladies dii Foie, 18S8.

UauieviUe : Des Tumours fornixes par la Vciiculc Bilialro. Th^e, Paris, 1873.

Hayem : Villard's Synop. Table.

llein: Ber. d. k. k. Krankenaast. Rudolph-Stiftuiig In Wien (1881), 1882, p. 294.

Heitlcr: Wiener med. Woclienschr., 18Si, No. 32, p. »8i).

Ilenrof. Bull. Soc. Med. de Kelms.. 1871, XIII, p. 23-3:j.

Ileytelder: Arcliiv Gen. de Med., 1839, T. 6, p. 444-4t«.

llosehl : Ein Fall von Zottenkrebs der Gallenblase. Ztsi^hr. d. k. k. Gesellscli.

d. Aerzte zu Wien, 1852, II. p. 251. leery: Cancer de la Vfoicule Bilialre. Bull. Soc. Auat., 1853, XXVIII, p.

73-76. Kiemann: Ber. d. k. k. Krankenanst. Rudolpb-Stiftungr in Wien (18791, 1880,

p. 339. ICIebs: Haudbucb der patb. Anat., Berlin, 18(19. Klobe, .1.: Ueber Zottenkrebs der Gallenblase. Wchndl. d. k. k. Gesellscli. d.

Aerzte zu Wien, 1856, II, p. 749-75.3. Kocher: Orig. K. Gesch. Inselspital, Bern, 1888. Koch, G.: Ein Fall von Carcinom der Gallenblase. Ber. kiln. Wochensclir.,

1880, XVII, p. 19«-1»8. Kohn : Der primfue Krebs der Gallenblase. Dissert, Breslau, 1879. Krauss, J.: Deutsch. .Archiv f. klin. Med., 1884, Bd. 34, p. 270. Lacaze : Bull. Soc. Anal., 1847, p. 355. Lambl : Virchow's Archiv, 18,55. Ijincercaux : Trait£ d'Anat. Path., T. I, p. 410 et 455. Lancereaui; SC-main M^dieale. 7, 1887, p. 334I.andau : Movable Kidney. Syd. Soc. Pub., 1889, CX, p. 325. Lang-IIeinrich : Vier FiiUe von Gallenblasencarcinom. Halle, 1881. Lebert: Traiti d'Anat. Path., etc., Paris, 1857, T. II, p. 325. I.ermoyez: Le Prog. Medical, 1884, p. 109.5. Lerou.v. H.: Prog-res M6dical, 1880, VIII, p. 390. Leuf : Proc. Med. Soc. Kings Co., N. Y., 1883, VIII, p. 291. Liebinan, C: Carcinoma della Clstifellea. Rosoconto Sanitano dell 'Osp. Civ.

di Trieste, 1876, 1-4, p. 211. Littre : Diet, de Med., T. V, 2nd edition. Loomis, H. P.: Jledical Record, N. Y., May 10, 1890. Lutton : Xouveau Diet, de Med. and de Chir. Pratique, 1860, V. 54. Mataieux : Bull. Soc. Anat., la'W. p. 180. '

Marchand, F.: Deutsch. med. Wochen., 1888, XII, p. 221. Markham : Tr. Path. Soc. London, 1856-57, VIII, p. 243. Martin : Ber. klin. Wochen., 1879, No. 22 u. 23. Martins: Ueber primiiren Krebs d. Gallenblase. Munchen, 1891. Moor, N.: Tr. Path. Soc. London, 1879-1880, XIII, ]>. 138. Mears : Tr. Amer. Surg. Assn., 1889. Morin : Contribution a I'fitude d'Epitheliome prlmitif de la Vesicule Bilialre.

These, Paris, 1891. Moxon : Tr. Path. Soc. London, 1867, XVIII, p. 140-142. Mulot': Bull. Soc. Anat., 1882, LVII, p. 171-175. Murchison ; Lectures on Diseases of the Liver, etc. London, 1868. p. 540, case

XCVI, and p. 543-545. Muschold : Dissert., Berlin, 1876. Musser, J. H.: Tr. Assn. Amer. Physicians, 1889; also Phil. Med. Times, 1880-81,

XI, p. 730-732. Naunyn : Klinik der Cholelithiasis, 1892, p. 153.

Niemeyer, E.: Beitrag z. Kasuistik d. Geschwillste d. Gallenblase u. d. Oallen wege. Dissert., Wurzburg, 1888. Notta: Bull. Soc. Anat., 1847, XXII, p. 335-337. Oettinger: Prog. Med., 188.5, 25, 1, p. 414. Ogle, J. W.: St. George's Hospital Reports, 1868. Osier aud Bell: Canada Med. and Surg. Journal, April, 1877. Owen, I.: St. George's Hospital Reports, 1879, X, p. 35. Path. Inst. Basel: A. S., 325, 1874, sect. 105; 1882, sect. 156; 1882, sect. 328; 1883,

sect. 8 ; 1883, sect. 291 ; 1884, sect. 237 ; 1888, sect. 296 ; 1888, sect. 85. Paulicki, A.: Carcinom d. Gallenblase. Ber. klin. Woch., 1867, IV, 348. Pepper, W.: Am. Jour. Med, Sc, Phila., 1857, n. s., XXXIII, p. 13--26. Pertik : OwOsI Hetilap. Pest. Med.-Chir. Pressc, 1885, XXI, p. 157. Peters, H.: Dissert., Kiel, 1890. Phillipp: Dissert., Greifswald, 1888, p. 10-21. Planteau: Bull. Soc. Anat., 1875, L, p. 689-692. Prompt: Bull. Soc. Anat., 1866, XLI, p. 374-376. Quetsch : Ber. klin. Wochenschr., 1885, No. 42. Quinlan: British Medical Journal, Feb. 28, 1874. Ramon: Cronica Medico-Quir. de la Habana, 1879, V, p. 81. Remy : Bull. Soc. Anat., 1885., p. 203-205. Renaud : London Medical Gazette, 1848, n. s. VI, p. 340. Rickards : Lancet, London, 1872, II, p. 659. Riedel : Berlin klin. Wochen.. 1888, No. 30, p. 603. Rippoll : Bull. Soc. Anat., 1849, XXIV, p. 359.

Robertson and Fitzgerald: Australian Med. Journal, 1871, n. s. 9, p. 221-223. Rokitansky: Path. Anat., Syd. Soc. Translation, Vol. II, 161. Salisbury, J. H.: Chicago Med. Jour, and Examiner, 1879, XXXIX, p. 29-31. Schmidt's Jahrbiicher, 1873, Bd. 160, p. 74.

Schmidt, F.: Ein Fall v. primiiren Gallenblasenkrebs. Dissert., Kiel, 1891. Schreiber: Ber. kiln. Wochen., 1877, No. 31.

Schrotter : Bericht. d. k. k. Allgemeinen Krankenhauses zuWien, 1881-1882, p. 23. Schueppel, V.: Ziemssen, Vol. VIII, Krankheit d. Gallenwege, p. 68. Smith, P.: Tr. Path. Soc. London, 1865-66, XVII, p 465. Smith, W. G.: Tr. Royal Ac. Med. in Ireland, 18S8, VI, p. 367-369. Socin: Orig. K. Gesch. Chir. Abtheg. Spital, Basel, 1889. Spohr, R.: Ein Beitragzur Pathogenese des Gallenblasenkrebses. Dissert.,

Giessen, 1892. Stiller, B.: Pester Med. Chir. Presse, Nos. 35-38, 1886. Stokes : Duljlin Q. J. Med. Sc, 1865, XXXIX, p. 218. Stoll : Ratio-Medendi, Wien, 1777, Ps. I, p. 290. Tiedmann: Zur Kasuistik des primiiren Gallenblasenkrebses. Dissert., Kiel,

1891. Topinard : Socii-te Anat., 1856, p. 239. Tyson, J.: Phila. Med. Times, 1873-74, IV, p. 652. Villard : Bull. Soc. A nat., 1870, p. 217. Voss : Norsh. Mag. f . LSgend, Bd. XXIV, p. 167. Walshe : Nature and Treatment of Cancer. London, 1846, p. 331. Wagner, E.: Primftrer Krebs der Gallenblase. Archiv d. Heilk., Leipzig, 188S,

IV, p. 184. Weber, W.: Dissert., Wttrzburg, 1891. Wells, T. S.: Lond. Med. Times and Gazette, 1878, 1, p. 871. Wigglesworth : Medico-Chir. Journal. 1887, VII, p. 217. Willigk, A.: Virchow's Archives, 1869, Bd. XLVIII, p. 524. Zenker: Deutsches Archiv Hir klinische Medicin, Bd. 44, 1889, p. 159.

PROCEEDINGS OF SOCIETIES,

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of April 2(1, 1894.

Dr. Kem.y in the chair.

Myoma complicating Pregnancy aud preventing nelivcry.— Porro-Csesarcan Operation niodifled by dropping the Pedicle.— Dr. Kki.i.y.

This patient is presented before the Society this evening, as she leaves the liospital in a short time, and I wish to review briefly the case, especially the reasons for submitting her to Cesarean Section.

She was referred by lier physician to the Johns Hopkins Hospital in theseventli month of her pregnancy, with the statement that she liad a fibroid tumor preventing delivery.

Examination revealed a myoma about the size of a large orange springing from llie posterior wall of the cervix, and two of smaller size on the anterior wall of the fundus. The cervical tumor blocked the inferior strait, preventing delivery of the fcetua, and was bo

closely wedged into the pelvis as to render myomectomy, craniotomy, or its displacement upward impossible, and thus there was but one other measure to be considered, that of C.'csarean Section.

The date of her confinement was calculated as nearly as possible, this being rather difficult to determine accurately on account of the irregular menstruation occasioned by the myomata, and she was submitted to operation near her full term.

The preparations for operation were the same as for ordinary coeliotomy. The abdominal incision was made from above the symphysis to a short distance above the umbilicus, and the uterus delivered upon the abdomen. In opening the uterus I cut through one of the myomata and the hemorrhage at first was quite profuse.

The child was rapidly delivered, and the cord was immediately clamped with artery forceps and cut. In the meantime Dr. Russell controlled the hemorrhage by grasping the cervix below the tumor.

As the danger of subsequent hemorrhage in these myomatous uteri is very great I determined to do a Porro-Cresarean operation, modified by dropping the pedicle. Accordingly I introduced tem

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8]

porary sutures through the uterine incision to control the slight tendency to hemorrhage at this point, and proceeded with the hysterectomy according to the method which I have adopted for the removal of large myomatous uteri.

The ovarian and uterine arteries were ligated on either side and the uterus amputated below the cervical tumor.

The flaps of the uterine stump were then accurately approximated with silk sutures, covered with peritoneum and dropped back into the pelvis. The abdominal incision was closed with buried silk sutures and the skin approximated with a subcutaneous silk suture. No drainage.

The patient leaves for home to-morrow, four weeks from the time of operation, having had an uncomplicated convalescence and now feels perfectly well. The baby died the night following the operation and the autopsy revealed atelectasis of the bases of both lungs.

lufusioii of Normal Saliue Solution in connection with Gynecological Operations and the Accidental Hemorrhages of Parturition. — Dr. Kelly.

During the past year I have employed infusion of normal salt solution a number of times in patients in extremis and I am certain that it has proved a life-saving measure in at least four cases.

The liability to hemorrhage in gynecological operations, especially in certain classes of pelvic diseases, is probably greater than in any other branch of surgery.

The blood-vessels of the pelvic organs are subject to the most varied distribution and displacement as a result of inflammatory disease and the growth of tumors, and when the tumor is a rapidly growing one and during pregnancy, the vessels often become very much enlarged and engorged. In some cases the vessels are exposed with the greatest ditBculty, and the patient may lose a large amount of blood before the bleeding vessel can be reached and controlled.

In the hemorrhage of parturition, either ante- or post-partum, this measure is undoubtedly of the greatest service, and I am certain that were it more generally employed by the general practitioners of our country the rate of mortality from post-partum hemorrhage would greatly be reduced. The first occasion on which I employed infusion, with signal success, occurred in an obstetrical case. I was called to see the patient one evening and found her complaining of vague pains which lacked the force and regularity of those of normal labor. The nurse called my attention to the fact that the patient had passed a small quantity of blood, and on examination I found a large clot in the vagina.

Foetal heart-sounds which had been present up to a short time before the beginning of labor were now absent. At tirst I suspected placenta pr;«via, but upon closer examination was unable to detect any evidence of this anomaly, and therefore concluded that it was a case of concealed hemorrhage. Proceeding upon this assumption I performed version and rapidly delivered the dead fcetus.

The amount of blood which poured from the uterus was enormous, and no one but a very strong and plethoric woman could have withstood such extreme depletion.

Never before have I seen a patient recover from such a hemorrhage. The pulse became very rapid and soon reached 160.

As there was still slight hemorrhage and the patient continued to have the severest cramp-like pains, I called assistants about five hours after the child was delivered, and after a careful examination under chloroform a piece of the placenta was found at the fundus uteri. The patient's pulse was now imperceptible and we resorted atonce to infusion, following the plan suggested by Dr. Clark, which is simply a reversal of the ordinary use of the aspirator.

The receiving-bottle of the aspirater was filled about two-thirds full of normal salt solution (.G percent.) at a temperatureof 105° F., the air-pump was reversed, forcing air into instead of exhausting air from the bottle, after which the stop-cock was closed and the

bottle inverted. While an assistant was preparing the apparatus for infusion I exposed the radial artery by a short oblique incision.

1 prefer arterial infusion, as the dangers from the entrance of air are less and the beneficial result more immediate than when a vein is employed for this purpose.

Before opening the artery two provisional ligatures should be passed beneath the artery, one above and one below the point of infusion.

After making a longitudinal slit in the artery the exit stop-cock was opened and the solution was allowed to flow before introducing the blunt needle of the aspirator into the artery ; in this way all possible danger of the entrance of air is avoided. In this case there was not the slightest bleeding on opening the artery, the pulse having been imperceptible for some minutes. About one litre of fluid was infused and the effect was remarkable ; hardly had the salt solution begun to flow when the pulse of the opposite wrist became perceptible and within a short time dropped to 125 and became quite full in volume. The convalescence in this case, although slow, was perfectly satisfactory.

Only one other instance of concealed hemorrhage occurring during parturition and treated by transfusion is reported.*

In many of its details this case of Dr. Taylor, reported in the London Lancet, is similar to the one which I have just presented to you.

He was called to see a woman who was supposed to be sinking during a protracted labor. The patient's pulse was nearly imperceptible, extremities cold, and she presented all of the symptoms of profuse hemorrhage.

Examination revealed the same condition as I have just described in my case, with the exception that the membranes were partially protruding. Uterine action had ceased and no effort was made to deliver the fcetus, but resuscitative measures were at once instituted.

About ten ounces of blood were transfused from the patient's sister, a strongly-built young Irish girl. The immediate effect of the transfusion was not so gratifying as in the case which I have just detailed, but on the whole her recovery was very satisfactory. The patient was delivered of a dead fcetus about twelve hours after the transfusion.

The results of infusion in three of my surgical cases have been no less gratifying.

In April, 1893, I removed the appendages of one side for a haematoma of the ovary in a young woman. During the afternoon of the same day her pulse suddenly began to increase in rapidity and soon all the signs of hemorrhage became pronounced.

I reopened the abdomen and found the pelvis filled with blood and active hemorrhage still continuing — the result of a ligature slipping from the ovarian artery. While I caught and religated the bleeding vessel, Dr. Russell transfused about one pint of salt solution. In this case the pulse quickly dropped from 150 to 130 and the patient made an uninterrupted recovery.

The second case was the one of which I spoke at a previous meeting of the Society.

This patient was already excessiTely aniemic from profuse hemorrhage, due to carcinoma uteri, and during my attempts to perform abdominal hysterectomy the bleeding became so profuse that I was compelled to ligate both internal iliac arteries. In this case 800 cc. of salt solution were infused.

In my last case profuse hemorrhage occurred the day after vaginal hysterectomy for carcinoma, and before it was arrested the patient had become pallid, was exceedingly restless, tossing from one side of the bed to the other, expression anxious and air hunger very pressing. The radial pulse had also disappeared in this case when the needle was introduced.

The results in these four cases have been very gratifying, and I feel that in all cases where hemorrhage has been so profuse as to

• Taylor, Londou Laucet, Vol. LXXII. p. 159.

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threaten life no time should be lost in at once resorting to transfusion.

The method just detailed is simple, and if properly carried out perfectly safe, and by its employment we give the patient the benefit of the slightest chance for recovery.

I would especially advise arterial infusion, as it is certainly less dangerous and the immediate stimulating effect is much more marked. The rapid gain in the volume of the jmlse on the opposite side is not due to the blood being forced back into the heart, but to the simple fact of resistance being supplied to the heart. The lluid is forced back to the first branches of the artery and thence gains access to the main circulation by passing through the capillaries. In this way the mixture of the blood and salt solution is more gradual than when the latter is at once thrown into the venous circulation and carried directly to the heart.

According to my judgment one or two and probably all of the patients just spoken of would have died had not infusion been employed.

Exhibition of Surgical Cases.— Dr. Finnev.

Appendkiiis. — In the absence of Dr. Halsted I will show some of the final results in cases operated on for appendicitis in the Johns Hopkins Ho8i)ital. "We sent word to all of the living cases asking them to come here to-night, but only seven have responded.

Since the Hospital was opened, Ho cases in all have been operated on : 30 males, 5 females ; 27 were adults, 7 children ; 25 cases recovered, 10 died. Operated during the first attack, 19 ; during some recurrent attack, 8 ; between attacks, 6. The appendix was removed wholly or in part in 24 cases, and abscess of th«> appendix was simply opened in 11 cases. There was general suppurative peritonitis present in 8 cases, and of those cases in which there was a record of the bacteriological examination of the pus, in 7 a pure culture of the colon bacillus was found, in 2 the green pus organism and in 2 pure cultures of streptococcus. There were 8 cases operated upon with general purulent peritonitis, all of which resulted fatally. All of these 8 cases were in extremis when operated upon, and of only one had we any hopes of recovery ; that one lived a week. It was a case of pure colon bacillus infection. The other 2 deaths were both cases in which a simple abscess had been opened. The one died on the second day from pneumonia with an acute nephritis complicating. The other case died on the fourth day with chronic nephritis ; the patient died in a comatose condition, and the autopsy revealed very small contracted kidneys. The latter was the oldest case operated upon, a man 72 years of age. TJie youngest was a boy aged 12.

Reviewing the cases hurriedly, we find representatives of almost every possible variation. They all gave, at the onset, a more or less typical history, suggesting possible trouble in the appendix ; later on other symptoms developed. One of the fatal cases had been treated by his family physician for 'i days for bladder trouble on account of difficulty in micturition. He had shown symptoms that undoubtedly suggested appendicular trouble, but they had been overlooked, and the one prominent symptom of dilliculty in micturition had attracted attention. When the patient arrived at the Hospital he was in a very bad way ; tlie abscess had ruptured, and there was a general peritonitis. This was a case in which the green pus organism was found. In two cases the abscess was located in the left iliac region instead of in the right. In neither had the disease been at first diagnosed, and when they reached the Hospital, one was almost moribund and the otlier extremely ill. Both were operated upon, and in each a general i)urulent peritonitis was found. We found that in each case there was an unusually long appendix, which had extended directly across to the left of the median line, just at the brim of the pelvis. The tip had been in each case the starting-point of the trouble. In the one it was gangrenous, in the other there wa.s a perforation. Both cases terminated fatally. Tliey were treated as are all the cases of general peritonitis, by as thor

ough cleansing of the peritoneal cavity as possible through the primary lateral incision, and later, if necessary, through a median incision. This cleansing process was done quickly, and the cavity drained with iodoform gauze. One of these cases was thought to be a case of volvulus, since the trouble had been located in the region of the sigmoid flexure and there had been absolute constipation for 4 or 5 days previous. In another case the abscess was situated so high up on the right side, and so close under the edge of the liver that it was impossible to differentiate it from liver abscess, although it was supposed to be a case of appendicitis at the time of the operation. In another case there was gangrene of the entire caecum. In this case there was also a general peritonitis. The man was very septic at the time of operation and soon succumbed. In still another case, the abscess cavity was extra-peritoneal at the time of admission to the hospital. Most of the swelling was below Poupart's ligament. The operation showed that the appendix had been shut off from the peritoneal cavity, and that the abscess had begun to burrow down the front of the thigh, in much the same way that a psoas abscess does. This case recovered. Another was one of so-called catarrhal appendicitis, pure and simple. It was the case of my roommate at college, whom I had watched for a long time. There was at no time any marked rise of temperature or tumor, but there was always a tenderness over the appendix, so much so that he was incapacitated for work. He came into the hospital at my suggestion and the appendix was removed by Dr. Halsted. He recovered and is perfectly well at this date, three years Later.

These cases illustrate very well different types of the disease, from the simple catarrhal varietj', to gangrene of the entire cfecum ; simulating a liver abscess, a twist of the sigmoid, or a psoas abscess covering pretty much the whole abdomen, and giving a wide latitude for differential diagnosis.

As far as the operation itself is concerned, we believe in operating in all cases in which there is definite indication of the existence of an inflammation of the appendix, with the following exceptions. If it is at the end of an attack, and there is given the history of preceding attacks, we rather advise waiting until this attack has subsided, operating in the interval. If it is the first attack, and a mild one, other things being equal, it is advised to wait until further developments. Of the six cases operated upon between attacks, all recovered, and in none of them at the present time is there a hernia. During the operation we isolate as much as possible the general peritoneal cavity from the seat of the trouble, by packing it off with sterilized gauze, or, in some cases, where there is considerable pus, with iodoform gauze. Of course, if there is one large pus cavity, that is simply drained, and unless the appendix presents in the wound, there is no attempt made to remove it. If there is only a little pus and the appendix can be found, which sometimes is a very difficult matter, it is separated from the adhesions and removed. A strip of iodoform gauze is inserted about the stump and brought out of the wound. Of course there is great objection to leaving the abdominal wound open, as there is always danger of a subsequent hernia, but this method seems to give the best results up to the present time.

Those of you who care to, may examine the results in the seven cases who are present. There is nothing to be seen, as you will observe, except in this man, who was operated upon about 15 months ago and the appendix removed. He now has a marked bulging of the scar almost as large as my fist. It gives him no inconvenience and he does heavy work right along. He has worn no abdominal support, contrary to our advice. In one of the other cases there is a slight impulse on coughing. I am sorry I cannot give a report on all the cases as to the existence of hernia.

Dr. Oslkr.— What is the objection to closing the wound in these instances of appendicitis unless there is extensive suppuration? I know a case of a physician in New York who has been much troubled after an appendix operation by just such a condition as was present in one of the cases shown here, namely, a very large hernia associated with which is a great deal of colic, possibly

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due to adhesions. If I understood him aright, his appendicitis was one without general suppuration, but it had been treated by the open method, and a very large hernia had developed in a very short time.

Dr. Finney. — I do not know that there is any objection in certain cases. The reason heretofore given for the open method has been fear of our inability to sufficiently disinfect the abscess cavity or the region about the stump. I believe that in many cases it is possible to so thoroughly disinfect this as to render it innocuous, and I propose when the next favorable opportunity presents, to close the wound tightly. A sufficient number of cases has been reported, I think, to justify such a procedure in selected cases.

Injury to the Slwulder. — This man, who applied to the surgical dispensary for treatment to-day, illustrates a very interesting form of injury to the shoulder-joint, the pathology of which I cannot satisfactorily explain. There is no description of this particular injury in any of the modern text books, so far as I am aware. It is in our experience in the dispensary, one of the commonest injuries met with in the shoulder-joint. It is brought about in a variety of ways. We have observed it following direct violence, for example a blow or fall, striking on the shoulder, or indirectly following heavy lifting or carrying heavy weights on the shoulder, etc. Ten days ago this man fell a few feet, striking on his elbow. Since that time he has been unable to do any work by reason of the intense pain produced liy motion of the arm. The condition is tliis : you cannot see any difference between the two shoulders on inspection. On palpation you will not feel anything different, unless occasionally a slight joint crepitus ; but you will notice an exquisitely tender point just beneath the coracoid process, and at times tenderness at a corresponding point oa the posterior aspect of the shoulder. There is always a disinclination to move the arm ; it hangs as if paralyzed. You can raise it without much difficulty to the horizontal position ; bringing it forward while held horizontally is the motion that produces the greatest pain. When you let go of the arm it drops as if helpless. Dr. Thomas has examined a number of these cases and has found nothing abnormal in the innervation. There seems to be no especial tenderness along the course of any of the nerves or muscles, unless l)ossibly over the short head of the biceps. Limited motion of the arm in any direction is attended by very slight pain. The joint itself, except at the points noted, is not sensitive to pressure. The treatment is quite satisfactory. The Paquelin cautery, applied daily, usually relieves the pain and brings back the motion of the arm in a very short time, in the recent cases. In the older cases the relief is not so rapid. The arm should be kept at rest for a few days.

Meeting of May t, 1894.

The Lesions caused by certain so-called Toxalbniuins.—

Dr. Flexner.

The crystalline principles called ptomaines which have been isolated by Selmi, Ncncki, Brieger and others, from cultures of bacteria do not, as was once supposed, represent the essentially active agents produced by pathogenic bacteria. Since the isolation of a poisonous albuminous principle from cultures of the bacillus diphtherire by Boux and Yersin in 1SS8, a number of albuminous substances have been obtained from pathogenic bacteria. The researches of Robert, Stillman, Martin and Ilcllin have resulted in the separation from the castor bean and the jequirity bean of two amorphous substances, ricinand abrin, which in many respects resemble tlie toxic albuminous principles obtained from bacteria. We owe to Weir Mitchell and Reichert our knowledge that the toxicity of snake venom depends upon certain albuminous constituents, and Mosso and Springfeld found an exquisitely poisonous substance in the blood of eels. Moreover, the well-known effects which the blood of one species of animal exerts ujion another species had led to the belief that the blood of different animals con

tains distinctly toxic substances. As to the precise nature of these substances, to which the name of toxalbumins has been provisionally given, there is little agreement. By some authorities they are regarded as enzymes, while a few deny altogether their albuminous nature.

The experiments which I wish to report to you briefly this evening consist of the study of the effects of some of these toxic albuminous substances upon animals, especially upon guinea-pigs, rabbits and mice. As has been indicated, the bodies derived from the several sources mentioned seem to possess certain chemical properties in common, and in considering their pathological action we shall find reason to treat them together. In considering for a moment the production of immunity, which, for many bacteria and their products, is an established fact, we find that evidence is not wanting for the toxalbumins derived from the higher plants, the phytalbumoses, whereas up to the present time no one has succeeded in rendering animals durably immune from the animal toxic proteids, although Sewall claims to have secured in pigeons an immunity from snake poison, which, however, disappeared after a time.

Ehrlich has shown us that mice, which are relatively quite susceptible to ricin and abrin, can be rendered in a high degree immune from the action of these bodies. I have repeated Ehrlich's experiments and confirmed his results ; and I have found, in addition, that immune mice which resist large doses of the drug when introduced subcutaneously, may still succumb to a similar quantity injected into the peritoneal cavity.

Having in mind the production of immunity to this substance, I have experimented on rabbits with dog's serum, but so far without success. On the contrary, I found that animals which had withstood one dose of dog's serum would succumb to a second dose given after the lapse of some days, or weeks, even when the dose was sublethal for a control animal.

The pathological lesions produced in animals by these various poisonous substances have been very imperfectly studied up to the present time. The contributions refer almost exclusively to the gross changes in organs and tissues, or consider simply the effect which is produced upon the blood, especially the alterations in coagulability. In the case of ricin or abrin poisoning, the pathological changes have been considered to depend upon an active gastroenteritis, thrombosis of vessels in the stomach and intestine followed by necrosis and ulceration from digestion. Just as little attention has been given to the tissue changes caused by the inoculation of foreign serum into animals. Heretofore it has sufficed to consider as the cause of death in the immediately fatal cases, the coagulation of the blood, especially in the right heart and main pulmonary vessels, or the production of widespread capillary thrombosis. All experimenters have, however, been confronted with cases in which, as death has been delaj'ed for several days, this explanation was insufficient, since thrombi were not demonstrable. Ponfick, however, has shown that the kidneys suffer injury in excreting the htemoglobin liberated by the breaking up of the red blooil corpuscles, and he attributes many casesof death to the resulting nephritis and blocking of the tubules with met-ha>moglobin c«sts. The microscopical study of the pathological changes in the organs has convinced me of the insufficiency of these views, and the extent and not the absence of tissue alterations is most remarkable.

Some three years ago Professor Welch and myself published a short communication on the lesions produced in the tissues by the soluble products of the diphtheria bacilli. This paper, following one describing the histological lesions in kittens, guinea-pigs and rabbits caused by the inoculation of the bacilli themselves, confirmed in all essential respects the first paper. These lesions are found extensively in the tissues, and are present in the lymphatic glands generally, in the spleen, liver, intestinal canal, kidneys and heart muscle. They are characterized, moreover, by a death of cells in the affected part, and they exhibit a decided tendency to occur in well-marked areas or foci, indicating that soluble sul>

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stances circulating in the blood are capable of producing focal lesions.

With a view of testing further the production of focal changes in the tissues by llie use of soluble poisons, I employed ricin and abrin. These substances, as already pointed out, resemble in many ways the bacterial poisons. One of the impressive results in their use was the certainty of their action. Robert showed that 0.03 mg. per kilogram of ricin was fatal to rabbits, cats and dogs, and Ehrlich's experiments indicated that guinea-pigs were so susceptible that one gram of the substance would suffice to kill no less than 1,5 10,000 of these animals. Up to the present time I have experimented upon mice, guinea-pigs and rabbits with these bodies and among my experimental animals I have had acute and chronic cases. The acute cases present such a characteristic picture that it is unmistakable.

The intravenous inoculation of ricin dissolved in 10 per cent, salt solution in the proportion of 0.3 mg. to 3 mg. per kilogram of weight kills rabbits in from 18 to 26 hours. The lymphatic glands generally are found swollen, tedematous and congested. The intestines are distended with faeces resembling cholera stools, and the patches of Peyer are greatly swollen and often hemorrhagic. The spleen is much enlarged, the kidneys congested, and the liver, besides being congested, presents foci to the naked eye of yellowish or yellowish-white color, which at times are surrrounded by hemorrhagic zones.

The microscopical changes were marked. In the lymph glands besides congested vessels and hemorrhages, many of the lymphatic elements were destroyed. Cells with fragmented nuclei were abundant and karyokinetic figures numerous. The lymphatic tissue of the intestines showed in an analogous manner the destructive action of the poison, and the spleen was affected in a manner similar to the lymph glands. The liver presented a variety of forms of cell death. The endothelium of the capillaries was sometimes necrotic, and the leucocytes in the vessels were often destroyed. The liver-cells in the yellowish or yellowish-white foci mentioned were necrotic, sometimes hyaline, or very pale and vacuolated, the nuclei not uncommonly having suffered fragmentation. Again, the liver-cells were converted into a reticulated structure resembling fibrin, and indeed the foci often gave a reaction with Weigert's fibrin-stain. In these organs the lesions tend to occur in distinct foci, and the areas of necrosis attract polynuclear leucocytes in considerable numbers.

We now know that certain stimuli of a chemical nature attract and repel leucocytes as well as other cells. In undergoing necrosis certain chemical changes take place in the tissues through which the leucocytes are attracted to them, but some bacterial products are still more positively chemotactic than are these substances derived from cells. Capillary tubes were filled with solutions of ricin in normal salt solution of varying strengths, 1 to 100,000, 1 to 200,000, 1 to 500,000 and 1 to 1,000,000, and introduced beneath the skin of rabbits. Control tubes of physiological salt solution were also introduced. After 20 hours the ricin solution of 1 to 100,000 proved to be strongly chemotactic. The weaker solutions exhibited positively chemotactic properties directly in proportion to the concentration.

Chronic ricin poisoning is associated with great disturbance of nutrition. There are wasting and evidence of great blood destruction. The kidneys in such a case exhibited atrophic patches.

I have also studied the lesions caused by the blood serum of one animal when introduced in another species of animal. Thus far my studies have been confined to the action of the blood serum of man and dogs upon rabbits. The inoculated animals, as often happens, may succumb immediately, in consequence of thrombosis

of the right side of the heart, the respiratory function ceasing before the heart's action. Not uncommonly the animal experiences less severe effects, and after a variable period of depression, increased frequency of respiration, weakness and hsemoglobinuria, apparently recovers. I have found dog's serum strongly globulicidal for rabbits. Doses of 1.5 per cent, of body weight were usually fatal, sometimes immediately, at others after 10 to 12 hours. Quantities of 1 per cent, caused profound disturbances, in rare instances death, while some animals appear to recover. In the last series death may occur after several days or weeks. These cases are of especial interest as lesions are found in the tissues. While the observations which I have made are more complete as regards the action of the serum of the dog upon rabbits, the serum derived from human beings apparently acts in much the same way. These lesions resemble, but are not identical with those described in connection with the toxalbumins of diphtheria, ricin and abrin.

In the acute cases degeneration of the epithelium associated with the presence of met-hsemoglobin casts are found in the kidneys. The spleen shows a tolerably rich fragmentation of nuclei and necrosis of cells situated especially in the malpighian bodies, and the liver contains foci of necrosis of liver cells. Of especial interest is an animal which died on the loth day. At the autopsy emaciation was marked ; the peritoneum contained an excess of fluid, the axillary glands were enlarged, the intestinal lymphatic apparatus apparently normal. The liver, which was firm in consistence, was roughened externally and dark in color. The kidneys appeared small, the capsule was not adherent, but the surface was granular. In the spleen were a number of white wedge-shaped areas, the bases at the capsule. Attached to the chord;e tendinse of the tricuspid valve was a calcified thrombus as large as a split pea. The urine contained albumin and casts. The microscopical changes were those of chronic interstitial processes in the liver and kidneys, while the wedge-shaped masses in the spleen looked like healed infarctions. In the liver the chronic changes were best studied and their relation to degeneration and necrosis of cells was evident.

In rabbits which died at a somewhat earlier period, after 5 to 6 days, I have found coagulation necrosis of liver cells. To these areas leucocytes are not attracted in such very large numbers, and in keeping with this I have found that capillary tubes containing dog's serum, when introduced beneath the skin of rabbits and removed after 26 hours, showed slight positive chemotaxis only.

In the end the differences in the action upon the tissues of the toxic agents discussed are not so great as their correspondences, a fact which emphasizes their chemical similarity. They so affect the tissue elements as to cause degeneration and death, and are followed by reparative processes which do not restore the integrity of the tissues. And, from this study of the changes in the tissues, we have seen that acute degenerative lesions, focal in character, maybe produced by soluble poisons, and these be followed by proliferation of the connective tissue of the parts, leading to chronic interstitial changes in the internal organs.

THE JOHNS HOPKINS HOSPITAL REPORTS.

KEPOBT IX GYNECOLOGY.

By HOWARD A. KELLY, M.D.,

Prnfettor of Gynccotoiry in the Johne Bopkins UniverMy and Gynecologitt to the Johns Hopkins Hospital.

This report containing 460 pages, large octavo, and 63 plates and figures, is now ready. It includes many papers of interest and importance to gynecologists. Price $3.00. Price of Vol. 3 complete, 15.00.

Tht John* Hopkint Hospital BuUetint are itiued monthly. They are printed by THB FRIEDBNWALD CO., Baltimore, from whom ringU eopie* may be obtained; they may al*n he procured from Met*r». CUKHING A CO. and the BALTIMORE NEWS COMPANY. Subscription*, $1.00 a year, may be addressed to TllK JOHNS HOPKINS PRESS, BALTIMORE ; single copie* will be sent by mail for Jif teen cent* each.

6681

BULLETIN

OF

THE JOHNS HOPKINS HOSPITAL.

Vol. v.- No. 42.

BALTIMORE, OCTOBER, 1894.

+++

Contents

Oliver Wendell Holmes. By Wm. Osler, M. D., - - The Leucocytes in Malarial Fever. By John S. Billings, Jr.,

M. D.,

On the Presence of Iron in the Granules of the Eosinophile Leucocytes. By Lewellys F. Barker, M. B., . - On the Value of repeatedly Washing out the Stomach at short

Intervals in Cases of Opium or Morphine Poisoning. By

L. P. Hamburger,

Death of James Carey,

PAGE.

- 85

80

PAOS.

The Bacillus of the Plague, 96

Proceedings of Societies : Hospital Medical Society, ---..--.98 Report of Twelve Cases of Complete Radical Cure of Hernia, by Halsted's Method, of over two years' standing. Silver wire sutures [Dr. Halsted] ; — Recent Results in Hysteromyomectomy [Dr. Kelly].

Notes on New Books, 101

Notice, 102

OLIVER ^VEI<^DELL HOLMES.

By Wm. Osler, M. I).

Very fitting indeed is it tliat be wlio hud lived to be " tbe last leaf upon the tree" should have falleu peacefully in tbe autumn which he loved so well. Delightful, too, to think that although he bad, to use the expression of Benjamin Franklin, intruded himself these many years into the comjiany of posterity, tbe freshness and pliancy of his mind bad not for a moment failed. Like his own wonderful "one-hoss shay,"' the end was a sudden breakdown ; and though he would have confessed, no doubt, to " a general flavor of decay " there was nothing local, and his friends had been spared that most distressing of all human sjjectacles, those cold gradations of decay, in which a man takes nearly as long to die as he does to grow up, and lives a sort of death in life, " ita sine vita vivcre, ita sine morte viori."

Enough has been said, and doubtless well said, by those who make ci'iticism their vocation, upon the literary position and allinities of Oliver Wendell Holmes, and I shall spare your perhaps already surcharged ears, lie has been sandwiched in my affections these many years between Oliver (ioldsmith and Charles Lamb. More than once he has been called, I think, the American Goldsmith. Certainly the great distinction of both men lies in that robust humanity which has a smile for the foibles and a tear for the sorrows of their fellow-creatures.

•Remarks made at th 15, 1894.

Johns Hopkins Medical Society, October

The English Oliver, with a better schooling for a poet (bad he not learned in suffering what he taught in song?), had a finer fancy and at his best a clearer note. With both writers one is at a loss to know which to love the better, the prose or the poetry. Can we name two other prose-writers of equal merit, who have so successfully courted the "draggle-tailed Muses," as Goldsmith calls them ? Like Charles Lamb, Holmes gains the affections of his readers at the first sitting, and the genial humor, the refined wit, the pathos, the tender sensitiveness to the lights and shadows of life, give to the Breakfast Table Series much of the charm of the Essays of Elia.

While it is true that since Rabelais and Liuacre uo generation has lacked a physician to stand unabashetl in the temple at Delos, a worshipper of worth and merit amid the votaries of Apollo, I can recall no name in the p;ist three ceuturies eminent in literature — eminent, I mean, in the sense in which we regard Goldsmith — which is associated in any enduring way with work done in the science and art of nietlicine. Many physicians, active practitioners — Sir Thomas Browne, for example — have been and are known for the richness and variety of their literary work ; but, as a rule, those who have remained in professional life have courted the "draggle-tailed Muses" as a gentle pastime, "to interpose a little ease" amid the worries of practice. Few such have risen above nuHiioority; fewer still have reached it. We know the names of Garth, of

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Arbiithnot and of Akeuside, but we neither knoAV them nor their works. The list is a long one, for the rites of Apollo have always had a keen attraction for the men of our auks, but the names fill at the best a place in the story of the literature of the countrj', not a place in the hearts and lives of the people. Far otherwise is it with a select group of men, Goldsmith, Crabbe and Keats, at the outset members of our profession, but who early broke away from its drudgery. In pride we claim them, though in reality no influence of their special studies is to be found in their writings. Two of these, at least, reached the pure empyrean, and to use Shelley's words, robed in dazzling immortality, sit on thrones

"built beyond mortal tlioiight, Far in the Unapparent."

Oliver Wendell Holmes may not reach the same exalted sphere, but he will always occupy a unique position in the affections of medical men. Not a practitioner, yet he retaiued for the greater part of his active life the most intimate connection with the profession, and as Professor of Anatomy at Harvard University, kept in touch with it for nearly forty years. The festivals at Epidaurus were never neglected by him, and as the most successful combination which the world has ever seen of the physician and the man of letters, he has for years sat amid the Esculapians in the seat of honor.

During the nineteenth century three schools in succession have moulded the thoughts and opinions of the medical profession in this country. In the early period English ways and methods prevailed, and (as in the colonial days) the students who crossed the Atlantic for further study went to Edinburgh or to London. Then came a time between 1835 and 1860 when American students went chiefly to Paris, and the profession of the country was strongly swayed by the teaching of the French school. Since 1800 the influence of German medicine has been all-powerful, but of late American students are beginning to learn that their " wanderjahren " should be truly such, and that when possible they should round out their studies in France and England.

In the thirties a very remarkable body of young Americans studied in Paris, chiefly under the great Louis — Oliver Wendell Holmes, James Jackson, Jr., Henry I. Bowditch and George C. Shattuck, from Boston, Swett, from New York, Gerhard and Stille, from Philadelphia, and Power, from Baltimore. They brought back to this country scientific methods of work and habits of accurate, systematic observation, and they had caught also, what was much more valuable, some of his inspiring enthusiam. So far as I know, one alone of Louis's A.uerican pupils remains, full of years and honors — Prof. Stille, of the University of Pennsylvania.

More than once in his writings Holmes refers to his delightful student days in France, and the valedictory lecture to his class in 1882 is largely made up of reminiscences of his old Paris teachers.

The fulness of Holmes's professional e(|uii>inent is very evident in his first contributions to medicine. In the years 1830 and 1S:J7 we find him successfully competing for the Boylston prizes, with essays on Intermittent Fever in New England, ou Neuralgia, and on the Utility and Imjirovement

of Direct Exploration in Medical Practice. Of these the essay on intermittent fever is in many ways the most important, since it contains a very thorough review of the testimony of the early New England writers on the subject, for which purpose he made a careful and thorough examination of the records of the first century of the settlements. Here and there throughout the essay there is evidence of his irrepressible humor. Referring to the old writers, he says, that because indexes are sometimes imperfect, he has looked over all the works page by jiage, with the exception of some few ecclesiastical papers, sermons and similar treatises of Cotton Mather, "which, being more likely to cause a fever than to mention one, I left to some future investigator." The essay shows great industry, and is of value to-day in showing the localities in which malaria prevailed in the early part of this century, and at the time at which he wrote. The essay on neuralgia is not so interesting, but is an exhaustive summary of the knowledge of the disease in the year 1836. The third dissertation, on direct exploration, of much greater merit, is a plea for the more extended use of auscultation and percussion in exact diagnosis. The slowness with which these two great advances were adopted by our fathers contrasts in a striking manner with the readiness with which at the present day we take up with new improvements and appliances. Aveubrugger's work on percussion dates from 1761, but it was not until the beginning of this century that the art of percussion was revived by Corvisart and Laennec ; while Piorry, as Holmes says, succeeded in creating himself a European reputation by a slight but useful modification in the art, referring to his pleximeter, of which in another place he says that Piorry " makes a graven image." The great discoveries of Laennec make their way very slowly to general adoption, and to this Holmes refers when he says, "it is perfectly natural that they (speaking of the older practitioners) should look with suspicion upon this introduction of medical machinery among the old, hard-working operatives ; that they should for a while smile at its pretensions, and when its use began to creep in among them, that they shoulil observe and signalize all the errors and defects which happened in its practical application."

Gerhard's work ou the diagnosis of diseases of the chest was published in 1836, and with this essay of Holmes's opened to the American profession the rich experience of the French school in the methods of direct exploration in all disorders of the chest and of the heart. Holmes's essay may be read to-day by the student with great profit; it is particularly rich in original references to the older writers. Headers of the Avtocrat and of others of Holmes's literary works have been surprised at the readiness with which he quotes and refers to the fathers of the profession, a facility readily explained by these Boylston prize dissertations ; and in their preparation he had evidently studied not only the modern authors of tlu' daj', but he had gone in the original to the great masters from Hippocrates to Harvey.

'J'ho j)rizo essay does not constitute the most enduring form of medical literature, and though the dissertation on Malaria is in some resj)ects one of the very best of the long series of Boylston essays, yet we could scai'cely have spoken of a medical

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

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reputation for Dr. Holmes had it to rest upon these earlier productions. A few years later, however, he contributed an article which will long keep his memory green in our ranks.

Child-bed fever was unhappily no new disorder when Oliver Wendell Holmes studied, nor had there been wanting men who had proclaimed forcibly its sjDCciflc character and its highly contagious nature. Indeed, so far back as 1795, Gordon, of Aberdeen, not only called it a specific contagion, but said he could jjredict with unerring accuracy the very doctors and nurses in whose practice the cases would develop. Rigby, too, had lent the weight of his authority in favor of the contagiousness, but the question was so far from settled that, as you will hear, many of the leading teachers scouted the idea that doctors and nurses could convey the disorder. Semmelweis had not then begun to make his interesting and conclusive observations, for which his memory has recently been so greatly honored.

In 184:2, before the Boston Society for Medical Improvement, Dr. Holmes read a paper entitled " The Contagiousness of Puerperal Fever," in which he brought forward a long array of facts in support of the view that the disease was contagious, conveyed usually by the doctor or the nurse, and due to a specific infection. At the time there certainly was not an article in which the subject was presented in so logical and so convincing manner. As Sidney Smith says, it is not the man who first says a thing, but it is he who says it so long, so loudly and so clearly that he compels men to hear him — it is to him that the credit belongs; and so far as this country is concerned, the credit of insisting upon the great practical truth of the contagiousness of puerperal fever belongs to Dr. Holmes. The essay is characterized in j^laces by iutenseness and great strength of feeling. He says he could not for a moment consent to make a guestion of the momentous fact which should not be considered a subject for trivial discussion, but which should be acted upon with silent promptitude. " No negative facts, no passing opinions, be they what they may or whose they may, can form any answer to the series of cases now within the reach of all who choose to explore the records of medical science." Just before the conclusions the following eloquent paragraphs are found, jiortions of which are often quoted : — " It is as a lesson rather than as a reproach that I call up the memory of these irre})arable errors and wrongs. No tongue can tell the heart-breaking calamities they have caused; they have closed the eyes just opened upon a new world of life and happiness; they have bowed the strength of manhood into the dust; they have cast the helplessness of infancy into the stranger's arms, or bequeathed it with less cruelty the death of its dying parent. There is no tone deep enough for record, and no voice loud enough for warning. The woman about to become a mother, or with her new-born infant upon her bosom, should be the object of trembling care and sympathy wherever she bears her tender burden, or stretches her aching limbs. The very outcast of the street has pity upon her sister in degradation when the seal of promised maternity is impressed upon her. The remorseless vengeance of the law bi'ought down upon its victims by a nuichinery as sure as destiny, is arrested in its fall at a word which reveals her transioiii claims for morcy. The solouin prayer of the

liturgy singles out her sorrows from the multiplied trials of life, to plead for her in the hour of peril. God forbid that any member of the profession to which she trusts her life, doubly precious at that eventful period, should regard it negligently, unadvisedly, or selfishly."

The results of his studies are summed uj) in a series of eight conclusions, and the strong ground which he took may be gathered from this sentence in the last one: "The time has come when the existence of a private pestilence in the sphere of a single physician should be looked upon not as a misfortune but a crime." Fortunately this essay, which was published in the ephemeral New England Quarterly Journal of Medicine, was not destined to remain unfloticed. The statements were too bold and the whole tone too resolute not to arouse the antagonism of those whose teachings had been for years diametrically opposed to the contagiousness of puerperal fever. Philadelphia was the centre of the teaching and work in obstetrics in this country, and if we can speak at all of an American school of obstetricians it is due to the energy of the professors of this branch in that city, and for the sake of the memory of the men we could wish expunged the incident to which I will now allude.

In 1852 the elder Hodge, Professor of Obstetrics at the University of Pennsylvania, published an essay on the noncontagious character of puerperal fever, and in 1854: Charles D. Meigs, Professor of Obstetrics at the Jefferson Medical College, published a work on the nature, signs, and treatment of child-bed fevers, in a series of letters addressed to students of his class. Both of these men, the most distinguished professors of obstetrics in America, took extreme ground against Holmes, and Meigs handled him rather roughly.

Nothing daunted, in the following year (1855) Holmes reprinted the essay, calling it Puerperal Fever as a Private Pestilence. He clearly appreciated the character of the work he was doing, since in the introduction he says, " I do not know that I shall ever again have so good an opportunity of being useful as was granted to me by the raising of the question which produced this essay." The point at issue is squarely put in a few paragraphs on one of the first pages ; the atlirniative in a quotation from his essay : " The disease known as puerperal fever is so far contagious as to be carried from patient to patient by physicians and nurses" (1843). The negative in two quotations, one from Hodge (1S52), who "begged his students to divest their minds of the dread that they could ever carry the horrible virus "; and of Meigs (1854), who says, " I prefer to attribute them (namely, the deaths) to accident or Providence, of which I can form a conception, rather than to a confaigion of which I cannot form any clear idea."

The introduction to the essay, which was reprinted as it appeared in 1842, is one of the ablest and most trenchant pieces of writing with which I am aotiuainted. There are several striking paragraphs ; thus, in alludiug to the strong and personal language used by Meigs, Holmes siiys : " I take no offence and attempt no retort ; no man makes a quarrel with me over the counterpane that covers a mother with her newborn infant at her breast." He apjwals to the moilical student not to be deceived bv the statements of the two distinguished

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 42.

professors wbich seem to him to encourage'professional homicide. One paragraph has become classical : " They naturally have faith in their instructors, turning to them for truth, and taking what they may choose to give them; babies in knowledge, not yet able to tell the breast from the bottle, pumping away for the milk of truth at all that offers, were it nothing better than a professor's shriveled forefinger."

The high estimate in which this work of Holmes' is held has frequently been referred to by writers on obstetrics.

Some years ago in an editorial note I commented upon a question which Dr. Holmes had asked in his " Hundred Days in Europe." Somewhere at dinner he had sat next to a successful gyiuvcologist, who had saved some hundreds of lives by his operations, and he asked, " Which would give the most satisfaction to a thoroughly humane and unselfish being, of cultivated intelligence and lively sensibilities: to have written all the plays which Shakespeare has left as an inheritance for mankind, or to have snatched from the jaws of death more than a hundred fellow-creatures, and restored them to sound and comfortable existence?" I remarked that there was nobody who could answer this question so satisfactorily as the Autocrat, and asked from which he derived the greater satisfaction, the essay on piicrperal fever, which had probably saved many more lives than any individual gynecologist, or the Chambered Ncmlilus, which had given pleasure to so many thousands. The jouriuil reached Dr. Holmes, and I read you his reply to me, under date of January 21st, 1889:

" I have rarely been more pleased than by your allusion to an old pajier of mine. There was a time certainly in which I would have said that the best page of my record was that in which I had fought my battle for the poor poisoned women. I am reminded of that essay from time to time, but it was published in a periodical which died after one year's life, and therefore escaped the wider notice it would have found if printed in the American Journal of the Medical Sciences. A lecturer at one of the great London hospitals referred to it the other day and coupled it with some fine phrases about myself which made me blush, cither with modesty or vanity, I forget which.

" I think I will not answer the question you put me. I think oftenest of the ' Chambered Nautilus,' which is a favorite poem of mine, though I wrote it myself. The essay only comes up at long intervals. The poem repeats itself in my memory, and is very often spoken of by my correspondents in terms of more than ordinary praise. I had a savage pleasure, I confess, in handling those two professors — learned men both of them, skillful experts, but babies, as it seemed to me, in their capacity of reasoning and arguing. But in

writing the poem I was filled with a better feeling — the highest state of mental exaltation and the most crystalline clairvoyance, as it seemed to me, that had ever been granted to me — I mean that lucid vision of one's thought and all forms of expression which will be at once precise and musical, which is the poet's special gift, however large or small in amount or value. There is more selfish pleasure to be had out of the poem — perhaps a nobler satisfaction from the lifesaving labor."

Last year at the dinner of the American Gyntecological Society in Philadelphia a letter from Dr. Holmes was read referring to the subject in very much the same language as he uses in his letter to me. One or two of the paragraphs I may quote. " Still I was attacked in my stronghold by the two leading professors of obstetrics in this country.

" I defended my position, with new facts and arguments, and not without rhetorical fervor, at which, after cooling down for half a century, I might smile if I did not remember how intensely and with what good reason my feelings were kindled into the heated atmosphere of superlatives.

" I have been long out of the way of discussing this class of subjects. I do not know what others have done since my efforts ; I do know that others had cried out with all their might against the terrible evil, before I did, and I gave them full credit for it.

" But I think I shrieked my warning louder and longer than any of them, and I am pleased to remember that I took my ground on the existing evidence before the little army of microbes was marched uji to support my position."

Fortunately, Dr. Holmes's medical essays are reprinted with his works. Several of them are enduring contributions to the questions with which they deal ; all should be read carefully by every student of medicine. The essay on Homeopathy remains one of the most complete exposures of that therapeutic fad. There is no healthier or more stimulating writer to students and to young medical men. With an entire absence of nonsense, with rare humor and unfailing kindness, and with that delicacy of feeling characteristic of a member of the Brahmin class, he has permanently enriched the literature of the race.

Search the ranks of authors since Elia, whom in so many ways Holmes resembled, and to no one else could the beautiful tribute of Landor be transferred with the same sense of propriety :

" lie leaves behind him, freed from grief and fears, Far nobler things than tears, The love of friends without a single foe, Unequalled lot below."

THE JOHNS HOPKINS HOSPITAL REPORTS, VOL. IV, Nos. 1, 2 and 3.

REPORT ON TYPHOID FEVER.

By \VM. OSLEK, M. D., Profaitor of Medicine, Jiiliim Hojj/.iiis University, and Phijsician-in-Chtcf to the Johns Ilopkim Hospital.

I.— General Analysis and Summary of the Cases. II.— Treatment. III.— Fatal Cases. IV.— Special Features, Symptoms and Complications, v.— "Typhoid Spine." VI.— Post-typhoid Aniumia. VII.— Urine and Kenal Complications. VIII.— Typhoid Fever in Baltimore.

107 pp., 6 charts. Price, $1.00.

Address The Jouns Hopkins Press, Baltimore, Md.

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

80

THE LEUCOCYTES IN MALARIAL FEVER

By John S. Billings, Jr., Assistant Resident Physician.

The blood in malarial fever has of late years offered a rich field for investigation, and many have been the articles and reports upon the subject since the discovery of the malarial parasite. These investigations have, however, been limited almost entirely to the malarial organism and the changes it brings about in the red corpuscles. Little attention has been paid to the leucocytes, and the literature on this part of the subject is scanty. The work done has been confined chiefly to the pigmented leucocytes which occur in the blood in malarial fever — -a question which does not concern us.

Rieder, in his work on the leucocytoses, refers briefly to the fact that Kelsch, Von Limbeck, Fahrmann and others have found no leucocytosis in malarial fever. Indeed, one or two of them state that the number of the leucocytes falls below normal.

Kelsch (Arch, de Physiol., 1875, p. 690, and 1870, p. 490) found the leucocytes diminished from one-third to one-half in malarial fever. He also states that at the beginning of the paroxysm there is a slight transient increase in the number of leucocytes in the blood. He found that the minimum number of the leucocytes corresponded to the maximum enlargement of the spleen, and that when the size of the spleen was diminished by means of an electrical current, there was a transient increase in the number of the leucocytes.

The most exhaustive article on the subject is that of Bastianelli (Bull. d. Real. Accad. Med. d. Roma, Ann. xviii, Fasic. V, p. 487). He occupies himself chiefly with the discussion of the pigmentation of leucocytes and phagocytosis. He refers to Golgi, who holds that phagocytosis occurs regularly as a function of the leucocytes, obtaining at definite phases of development of the organism. This phagocytosis is 'accomplished both by the j)olynuclcar leucocytes and the large mononuclear and transitional forms, while the lymphocytes and eosinophiles never contain jiigment. Golgi also believes that phagocytosis may account for the spontaneous recovery observed in so many cases, and that it pl.ays an imjiortant part in the prevention of all malarial fevers from becoming pernicious.

Bastianelli finds:

1. The number of leucocytes is always diminished in malarial fever.

2. The number of pigmented leucocytes increases markedly at the time of sporulation of the organism in the tertian cases ; i. e., at the beginning of the febrile paroxysm.

3. In cases of spontaneous recovery no increase is to be observed in the number of pigmented leucocytes. This phenomenon of phagocytosis may occur at all stages of the cycle of evolution of the organism in the i«stivo-autumnal cases.

4. The phagocytic leucocytes rapidly become necrotic and disappear from the blood. This probably accounts for the diminution in number of the leucocytes which takes place in malarial fever.

5. The phagocytosis is accomplished chiefly by the large mononuclear forms.

As regards the relative numerical proportions of the various forms of leucocytes, he only states that in post-malarial anaemia the percentage of the polyuuclear elements decreases, while that of the lymphocytes and large mononuclear elements increases.

The observations here reported were undertaken with the view of determining, if possible, whether any regular variations took place in the number of leucocytes in the blood during the febrile and afebrile periods of malarial fever.

Malaria is very prevalent in the immediate neighborhood of Baltimore, and we see three types of fever, as follows :

1. The spring or tertian type. This is most common in the spring and early summer, though cases are often seen in the autumn. The paroxysms occur every other day if the case be one of single tertian, and daily if it be one of double tertian ; I. e., with two sets of organisms in the blood, maturing on alternate days. This latter form is the commonest type we see here.

2. The quartan type. This is rarely seen, there being only five cases on record in the hospital. The paroxysms are rarely as severe as those in the previously mentioned type of the disease. They may occur every third day. two out of every three days, or every day, according as there may be one, two or three sets of organisms in the blood,

3. The fall type. This is the ajstivo-autumnal type of the Italian observers, and occurs in the late summer and fall. The course of the fever is irregular. There may be definit«  paroxysms, as in the tertian type of the disease, or the temperature may be continuously elevated for days. The paroxysms may occur daily, or there may be no regular periodicity.

The counts were made with the Thoma-Zeiss ha^mocytometer, the same instrument being used in each case. Care was taken that the counts shonld not be made within two hours after meals. In about iialf the ca^es the large one to twenty mixer was used, with the one-third per cent acetic acid solution as a diluting medium. In the remainder the smaller one to one hundred mixer was used, with Toisou's fluid as a diluent. The results obtained with the latter instrument seem fully as accurate as those with the former. Four whole fields were counted in each case.

The relative numerical proportions of the various forms of leucocytes were estimated by means of dried and stained coverglass preparations. These were luirdened by heat aocordiug to Ehrlich's method, and stained with the Ehrlich-Biondi triple stain as modified by Thayer. The counting was done with a mechanical stage, and tlie number of leucocytes counted varied. In all cases at least two hundred and fifty were counted, and in one or two as many as one thousand. The nomenclature used is according to Thayer, which is a modification of those used by Ehrlieh and Uskow. The lymphocytes and small mononuclear forms of Ehrlieh are given together under the head of small mononuclears, while the large mononuclear and transitional forms are classified together as large mononuclears. It is difficult to draw any hard and

90

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 43.

fast line between these two groups. Any mononuclear element one and one-half times as large as a red blood corpuscle was counted as a large mononuclear. According to this rule a large lymphocyte would be occasionally classified among the large mononuclears, while on the other hand the small transparent forms of Uskow would be counted among tlie small mononuclears. The difference was never more than one per cent, however.

The cases have been tabulated for convenience sake, and as little superfluous matter added as possible.

In looking over the table of tertian cases it is striking to note the uniform diminution in number of the leucocytes during the febrile paroxysm [leucocytolysis ?j. It is also to be noted that the maximum number of leucocytes is found as a rule two or three hours after the chill. From that time on there is a progressive diminution until the minimum number of leucocytes is reached at the end of the jiaroxysm when the temperature is subnormal, which it usually is for some hours. The number of leucocytes then rises somewhat, and during the interval occupies a position about midway between the maximum and mininuim above mentioned. The increase at the beginning of the paroxysm does not take place until after

the chill, as the average number of leucocytes just before the chill is very slightly higher than the average number during the interval. These points are well shown if the average number of leucocytes at the different stages of the paroxysm be represented graphically together with the average temperature at those times.

The strong objection to the occurrence of this apparently regular oscillation of the number of leucocytes is the fact that the differences involved are so extremely small as to almost come within the limit of error of the haemocytometer. This may be placed at two thousand at the outside, if sufficient care be taken. While we may be in doubt as to the occurrence of an increase in the number of leucocytes in the blood at the beginning of the malarial paroxysm,, there can be little doubt that there is a definite diminution in the number of the leucocytes toward the end of the paroxysm. The difference between the average maximum and the average, minimum number of leucocytes is 4271, which is well outside of the limit of error. The average number of leucocytes three hours after the beginning of the paroxysm is only 2300 more than the average number just before the beginning of the paroxysm. Yet this increase, slight as it may be, occurs in seven of our ten cases,

Black = leucocytes. Broken = temperature.

li

.s

No.

Patient.

Date Admitted. Previous Duration.

Type of Organism.

Date.

Hour.

p. a

3 S

-P.

Remarks.

5* » ? 2

o3 §0

lis

=2 0. 0-5

1.

K.-Malo, 26.

August 18, 1893.

Tertian

Aug. 18.

1P.M.

104.2°

3250

Beginning of chill.

68.2

15.1

15.6

1.1

White.

Illness began August 16, 1893.

(double).

4 P.M.

103.6°

>mo

73.2

11.9

14.1

.8

Daily paroxysms.

6 P. M. 12 mid.

lOl.O"

97.8"

4100 3000

63.4 54.7

15.3 20.5

20.3 33.8

2.1 1.

2.

M.— Male, 33.

August 16, 1893.

Tertian

Aug. 19.

1.45 P. M.

101°

5500

Beginning of chill.;

71.3

17.4

11.1

.2

White.

Illness began August 11, 1893.

(double).

Aug. 20.

10 A. M.

97.2°

4.500

08.

7.3

24.2

.5

Daily paroxysms.

10 P. M.

103°

2666

Chill began at 2 P.M.

.53.7

12.8

33.3

1.3

Aug. 21.

a A. M.

97°

2500

49.8

18.6

30.9

•'

3.

S.-Male, n. White.

August 31, 1893. Illness began August 14, 1891.

Tertian (single).

Aug. 23.

A.M. 10 A. M.

100.2° 103.6°

6000 7750

Beginning of chill.

82.1

12.1

5.1

.7

Paroxysms every other day.

11 A. M.

12 M.

1 P. M. 4 P. M.

103.2° 102.6° 100.1° 99°

7500 4750 5000 3500

Sweating.

75.8 66.'

7.1 22.4

lei

16.6

i.i ii

Aug. 24.

13 M.

98°

3750

65.1

23.7

9.2

2.

4.

Same case.

Aug. 25.

8 A.M.

102°

7350

Beginning of chill.

78.1

12.4

7.4

2.1

10 A. M.

104.8°

9750

79.2

8.1

12.4

.3

13 M.

103°

63.50

Sweating.

70 8

15.1

13.7

.4

3 P. M.

100°

6000

64.

13.5

21.5

1.

4 P. M.

98.6°

5350

8 P.M.

98.6°

5000

632

22!

8.8

6.'

6.

S.-Male, 20.

August 24, 1893.

Tertian

Aug. 34.

8 P.M.

98.6°

3000

63.1

21.8

14.

1.1

White.

Illness began August 10, 1893. Daily paroxysms.

(double).

Aug. 25.

11P.M. 13 P. M. 1 A. M.

105° 105° 104.9°

2350 3000 4300

Beginning of chill.

75.2

14.

10.2

.6

3 A. M.

104.7°

6750

7i.'6

7.'5

17.4

.5

3 A.M.

103.9°

4500

Sweating.

4 A. M.

103.2°

3250

5A.M.

102.4°

3500

oeis

17!

18.'

.2

6 A. M.

101.1°

3000

8 A. M.

98.4°

2600

76.'2°

26.'6

'•

'i

8.

B.-Male, 20.

August 2.5, 1893.

Tertian

Aug. 26.

8 A. M.

98°

6000

Just before chill.

66.9

22.1

I0»

.8

White.

Illness began August 20, 1893.

(double).

2 P.M.

105°

8350

71.

13 8

14.1

1.1

Daily paroxysms.

6 P.M.

99°

4100

Sweating.

61.3

15.7

32.6

.4

Aug. 37.

8 A. M.

98.6°

3000

50.4

20.4

39.2

.0

7.

P.-Male, 19.

August 28, 1893.

Tertian

Aug. 39.

10 P. M.

97.8°

5000

Just before chill.

70.6

14.5

13.8

11

White.

Illness began August 35, 1893.

(double).

12 P. M.

104.2°

6666

816

6.4

11.1

.9

Daily paroxysms.

Aug. 30.

12 M.

97°

2100

61.4

17.4

19.3

2.

S.

W.-Male, 27.

March 6, 1894.

Tertian

March 6.

1.15 P. M.

103°

5000

Beginning of chill.

73.2

8.

18.8

.0

White.

Illness began March 4, 1894.

(double).

4.15 P. M.

105°

63.50

80.2

6.9

12.6

J3

Daily paroxysms.

March 7.

8.m A. M.

97.9°

1500

43.2

28.

30.4

.4

March 8.

9 A. M.

98°

3100

488

27.2

13.

2.

March 9.

11 A. M.

98.0°

5750

50.8

30.1

8.9

,2

March 10.

11.30 A.M.

98.6°

5200

74.1

20.9

4.2

.8

9.

G.-Male, 22.

August 14, 1894.

Tertian

Aug. 15.

3.30 P. M.

100°

aioo

Beginning of chill.

73.8

13.

12.1

1.1

White.

Illness began August 9, 1891.

(double).

10 P. M.

101°

1.500

64.1

IH

21.

.8

Daily paroxysms.

Aug. 16.

8 A.M.

98°

5000

55.2

21.3

23.3

^

2.30 P. M.

98°

3000

Just before chill.

51.6

f&Ji

19.1

4j[

10.

J.-Male, 48.

August 14, 1894.

Tertian

Aug. 16.

12 M.

98.6°

5100

50.2

28.7

SO.

1.1

Blaclc.

Illness began August 6, 1894.

(double).

Aug. 17.

2 P. M.

101°

7000

Beginning of chill.

81.5

8.

10.

.5

Daily paroxysms.

5 30 P. M.

100.6°

57,50

Sweating.

72.8

9.1

17.1

1.

10 P. M.

98°

2000

58.

13.5

28,

.5

11.

n.— Female, 13.

August 24, 1.S93.

/Estivo

Aug. 27.

8 P. M.

103.2°

4.500

I Temperature not normal

62 8

27.6

9.6

.0

White.

Illness began August 14, 1893.

autumnal.

Aug. 28.

8 P.M.

101.7°

2200

f since admission.

69.9

20.4

9.5

Jt

Irregular fever since that date.

Aug. 30.

8 P.M.

98.2°

3500

First normal temperature.

63.1

7.1

i9.6

12.

T.— Male, 8.

September 2, 1893.

.Estivo

Sept. 3.

10 A. M.

99.8°

6100

Irregulfir fever temp, not touching normal for 3 days.

54.1

22.

22.1

.1

White.

Illness began August 12, 1893.

auturaual.

6 P. M.

102°

4200

69.2

IS.

113

1.5

Irregular I'over since that date.

Sept. 4.

4 P. M.

104.6°

5200

i. e., until the 5th.

4Ji.l

20.2

S1.3

.4

Sept. 5.

8 A.M.

99.2°

6500

&5.5

19.9

13.6

1.

13.

C.-Male, 30.

September 11, 1893.

.Kstivo

Sept. 11.

4 P. M.

105°

64 OO

Height of febrile paro.\jfm

73.1

16,7

11.2

.0

Black.

Illness began September 0,1893.

aut\imnal.

Sept. 12.

8 A.M.

98.8°

3500

lasting 24 hours.

70.6

12.4

13.9

3.1

Irregular fever with uight

P.M.

98.6°

4000

6S.7

12 7

18.1

.5

sweats.

U.

C.-Male, 27.

September 16, 1893.

yEstivo

Sept. 17.

8 A. M.

98.6°

2100

c-..;_i

12.7

20.6

1.4

White.

Illness began August 7, 1803.

autumnal.

8 P.M.

101.4°

3500

Height of iiaroxysni la.stinc 20hours.

f."^.7

is.rt

12.1

.6

Irregular febrile paroxysms

Sept. 18.

12 M.

98.6°

34(0

.v.».

24.7

10.1

—

with sweating.

15.

M.-Malc, 20.

August 16, 1894.

vEstivo

Aug. 16.

3.30 P. M.

101°

51.50

Temp, falling.

69.6

1.-5.I

16.2

1.1

Wliite.

Illness began .August 12, 1894.

autumnal.

Aug. 17.

10 A. M.

99°

67.50

Temp. Iwgan to rise at 2 P- -M.

,53..5

23.5

23.

1.

Irregular febrile paroxysms

5 P. M.

100.7°

4200

45.1

S3.7

30.

1.3

with cliills and sweating.

10.

K.— Male, 13.

.luly 19, 1891.

Quart-an.

•luly 21.

8 A. M.

98.4°

5.50O

B9.1

34.9

15.7

.S

White.

Previous history uot obtainable.

July 22.

S P. M. 8 A. M.

100.5° 98.6°

6100 6200

Height of slight pjtroxysm.

61.3 68.

J7.8 17.2

1S.S 1&.1

92

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 42.

and until proof to the contrary be offered, we are justified in thinking it to take place regularly. The relative numerical proportion of the various forms of leucocytes is stated by Ehrlich to be as follows :

Polynuclears, 70 to 75 per cent ; lymphocytes, 15 to 25 per cent; mononuclear and transitional forms, 6 per cent, and eosinophiles, 1 to 5 per cent.

Uskow gives it as follows : Tjymphocytes and small mononuclears, 18 per cent; transparent and transitional forms, per cent, and polynuclears and eosinophiles, 76 per cent. The two classifications practically correspond, and we will adopt the latter as our standard.

Taking up first the polyuuclear leucocytes, it is seen that they arc markedly diminished, both relatively and absolutely. In one case (No. 8) they are as low as 43.2 per cent. The greatest reduction is, as a rule, at the end of the paroxysm. In six cases there is a distinct increase in their number during the first three hours of the paroxysm, corresponding to the increase in number of the leucocytes as a whole. The small mononuclear elements vary widely, from -30.1 per cent in Case 8 to 6.4 per cent in Case 7. Nothing definite is to be made out concerning the variations in their percentage.

The large mononuclear elements are, as a rule, greatly increased, both absolutely and relatively. The highest count is 33.2 per cent in Case 2 ; the lowest, 4.2 per cent in Case 8. They are above normal in all but two instances, and seem to reach their maximum towards the end of the paroxysm, thus counterbalancing the polyuuclear forms, which reach their minimum at that time. The percentage of eosinophiles is rather below normal, but nothing worthy of note is to be made out concerning them.

In the cases of malaria of the fall type it is impossible to arrive at as definite conclusions as in the tertian cases. The onset of the paroxysm is almost always gradual, the temperature rising and falling relatively slowly as compai-ed to the temperature in the tertian cases. The paroxysms average about 36 hours in length. It seems, however, from our cases that there is a distinct though slight diminution, in number of the leucocytes at the end of the paroxysm, the reparation in number of the leucocytes taking place during the interval. The polyuuclear elements are distinctly decreased in number, while there is a corresponding increase in the number of the large mononuclear elements. The small mononuclears and the eosinophiles seem relatively unaffected.

In the one case of quartan malaria which came under observation, no variations in number of the leucocytes could be made out. The differential count of the leucocytes, however, showed the same condition of affairs already noted in the tertian and fall cases.

Besides the observations here reported, a sufficient number of extra counts were made to bring the total number of counts up to one hundred, the average result Ijeing 4323. .So that if we take 7<iO() per cmni. as the average normal number of leucocytes in human blood, in malarial fever there is on an average a diminution of about 38 per cent.

This is possibly to be explained as Bastianelli says, by the necrosis of the phagocytic leucocytes which have taken up altered blood pigment, malarial organisms and degenerated

red blood corpuscles. At any rate the diminution in number of the leucocytes does occur, whatever nuiy be the cause.

The average numerical proportions of the various forms of leucocytes in the 16 cases are as follows:

Polynuclears. Small Mononuclears. Large Mononuclears. Eosinopliiks. 65.04 per ct. 1G.9 per cent. 16.9 per cent. 0.96 per cent.

The increase in the number of the polyuuclear forms just after the chill is to be explained possibly as a manifestation of chemotaxis due to toxiues circulating in the blood, or as an evidence of regeneration.

The confusion of typhoid with malarial fever, especially the fall type of the latter, is something that we must be on our guard against. In the latter form of malarial fever the temperature is often elevated for days, the patient is dull and listless, the tongue is heavily coated, the sjjleen is readily palpable, and Ehrlich's diazo-reaction occurs in the urine. In short, with the exception of the absence of the diarrhoea and rose-spots, there is a tolerably complete picture of typhoid fever. In Cases 11 and 12 the temperature remained elevated for four and three days respectively. The organisms of this type of malarial fever are very easily overlooked. For the first week or so after the beginning of the illness the only forms of organism present in the peripheral circulation are the so-called "hyaline" bodies. These are very small, and to one unaccustomed to examining malarial blood are readily confused with vacuoles in the red corpuscles. The crescentic forms of the organism do not appear until later in the disease, and the segmenting forms are not found in the peripheral circulation.

Uskow has called attention to the fact that in typhoid fever there is no leucocytosis, and that there is a diminution in the percentage of the polyuuclear leucocytes with a corresjjonding increase in the percentage of the large mononuclear forms. This he believes to occur regularly in uncomplicated cases of typhoid fever, and his statement has been verified by a number of counts made by Dr. W. 8. Thayer and myself at the .Johns Hopkins Hospital. But this condition of the blood is exactly the same as the one which obtains in malarial fever of the fall or ffistivo-autumnal type. So that the estimation of the number of leucocytes, and the determination of the proportions of the various forms by means of stained specimens, are not sufficient for the diagnosis of typhoid unless we can definitely rule out the presence of malarial organisms.

In conclusion, a few words may be added about the leucocytes in malarial anemia.

While the occurrence of a leucocytosis in most secondary anannias is the rule, it is never very marked, rarely being above 15 to 18,000. In four cases of malarial ana-mia which we have had under observation the increase in the number of leucocytes was striking. In two cases where the red corpuscles ranged just above 3,000,000 per cmm. the leucocytes were 28,000 and 30,000 respectively. In another case the red corpuscles were just under 2,000,000, while the leucocytes reached 40,000. In the fourth ease the red corpuscles were 3,600,000, a relatively mild anremia, while the leucocytes ranged above 20,000 for a week. In all four cases the increase was solely in the polyuuclear leucocytes.

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

93

ON THE PRESENCE OF IRON IN THE GRANULES OF THE EOSINOPHILELELTCOCYTES.

By Lewellys F. Barker, M. B., Associate in Atiatomy, Johns Hopkins University.

A short time ago, while, making some experiments concerning the metabolism of the parasites of malaria, I treated a number of smeared cover-slip preparations of blood taken from patients suffering from the disease, with reagents used for the micro-chemical demonstration of iron.

Among other tests, the delicate method elaboi-ated by Macallum* of Toronto, for the demonstration of iron in chromatin, was employed. Dr. Macallum has found that by treating freshly teased cells from various tissues, both animal and vegetable, Avith a mixture of recently prepared ainmonium snljjhide and glycerine, and leaving the jjreparation on a glass-slide under a cover-glass in the thermostat at 60° 0. for some days, that the chi'omatiu of the cell-nuclei assumes a distinct green or greenish-black tinge, indicating the presence of iron. He was able to demonstrate, too, in his experiments on the absorption of ironf in certain animals, the presence of that metal in the epithelial cells of the intestine and within the protoplasm of many leucocytes, especially at the beginning of the central lacteals in the villi. Iron, not demonstrable by the ordinary micro-chemical reactions, ("masked iron "), could easily be rendered apparent by the prolonged action of the heated sulphide and glycerine, especially if teased preparations were used so that the reagent could surround on all sides the cells to be acted upon.

In my experiments, cover-glass preparations, such as are employed for the color-analysis of the leucocytes according to the methods of Ehrlich, were heated on the copper bar at a temperature of 12(1° C. for from one to two hours, and were then treated in the following way: A drop of solution of ammonium sulphide, prepared just before using, was placed upon the smeared surface of the cover-slip, and this was immediately laid upon a drop of glycerine, the glycerine and sulphide-solution mixing, upon a large thick glass-slide. The jireparation was then placed in the thermostat at 60° C. t)nce as early as after 6 hours, but usually at the end of 24 hours, and more markedly at the end of 48 hours, the greenish-black iron reaction in the chromatin of the nuclei of the white corpuscles was apparent in the specimens. By this time the hiBinoglobin of the red corpuscles had assumed only a slight

• Macallum, A. B., On the demonstration of the presence of iron

in chromatin by micro-chemical methods. Proc. Roy. Soc, Vol. 50. f Joui'nal of Physiology, Vol. XVI, Nos. 3 and 4.

greenish tint. In an occasional leucocyte, however, granule.^ of the size and shape of the eosinophile granules were veiT distinctly stained yellowish-green.

To make sure that the granules were really those of the eosinophile-leucocytes (although the morphology of these granules is in itself so typical that they can as u rule be recognized in fresh unstained specimens of blood), some cover-slip preparations known by control-studies of slides stained with the triple stain to contain a much larger number of eosinophile-leucocytes than normal, were submitted to the same test. In these too the eosinophile granules stained sharply. The blood taken from a patient whose blood contained 18 percent, of eosiuophiles yielded very striking pictures.

The granules in the sulphide-glycerine preparations do not assume quite the same tint as do the nuclei of the leucocytes ; the latter are stained greenish-black and have a dull appearance; the eosinophile granules by contrast are more highly refractive, and while stained greeuish-black show also a slisrht yellowish tint.

The finer neutrophilic granules within the protoplasm of the leucocytes with polymorphous nuclei do not yield anv visible iron-reaction.

Sherrington in his article* on the changes in the leucocytes, in certain infiammatious, describes carefully the various forms of white corpuscles, including the eosinophiles (coarselv grauular leucocytes). He did not notice any marked alteration in the coarse granules on treatment with ammonium-sulphide (p. 300), probably because the specimens were not submitted to the high temperature necessary for the demonstration of •• masked " iron. Sherrington found, however, that witli the ammonium-molybdate test as applied in micro-cheuiical work by Lilienfeld and Monti, that the eosinophile grauuk'S yielded a distinct though faint reaction for phosphorus. He also convinced himself of the presence of a basophilic membi-.ine surrounding the eosinophilic (oxyphile) granules.

The significance of the leucocytic granulations is as yet not fully understood. An attempt has been made to assign to the eosinophile granules a definite function in protecting the organism against bacterial invasion. It may be that the results of the micro-chemical test.s above referreti to will be of some aid in coming to a conclusion reganiing their import

• Proc. Roy. Soc, Vol. LV, No. 332, pp. 161-20«>.

THE JOHNS HOPKINS HOSPITAL REPORTS. VOL. IV. Nos. 4 and 5.

By henry J. BERKLEY, M. D.

Contents: I.— Dementia Paralytica in the Negro Race. IT.— Studies in the Histology of the Liver. III.— The Intrinsic Pulmonary Nerves in Mammalia. IV.— The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates. V.— The Intrinsic Nerves of the Submaxilhuy Gland of .^f<is mutculm. VI.— The Intrinsic Nerves of tlie Thyroid Gland of the Dog. VII.— The Nerve Elements of the Pituitary Gland.

Price, $1.50. .\ddress The .Tohns Hopkins Press. B.vltimorb, Md.

94

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 42.

ON THE VALIJE OF REPEATEDLY WASHING OUT THE STOMACH AT SHORT INTERVALS^ IN CASES OF OPIUM OR MORPHINE POISONING.

By L. p. Hamburger. (From the Pharmacological Laboratory of the Johna Hopkins Unirersity.)

Ainoug the many researches that have been made on the physiological, therapeutical aud toxicological properties of morphine since its isolation by Sertiirner in 1817, those of Marme,* Leineweber,t A]t,J aud Tauber,§ demonstrating its elimination by the gastric mucous membrane take a leading place. The medical profession in general does not seem, however, to be familiar with the practical applications that may be made of this discovery and it is worth while to record the following case of opium-poisoning in which a chemical examination was made of the urine and of successive stomach washings, especially since the results agree with those found by the above-mentioned investigators in their experiments on animals.

On the evening of May 2, 1894, 6G0 cc. of a sherry-red fluid was sent from the hospital to the pharmacological laboratory, the liquid being part of the washings of the stomach of a Chinaman, Lee Hee, who had attempted suicide.

A report was requested as to the kind of poison ^that had lieen taken. The fluid was clear, with a few bits of orange pulp floating in it, and it smelled faintly of crude opium; it w-as liltered and gave the characteristic mecouic acid reaction, luimelv, the red color with ferric chloride or ferrous sulphate which persisted on the addition of hydrochloric acid and also when boiled. A second portion of the filtered fluid was made alkaline with sodium hydrate, shaken up with ether, the ether removed and evaporated, the yellowish-white residue from the ether dissolved in a little acidulated water and this solution examined for alkaloids. It responded perfectly to the following reagents : platinic choloride, iodine in potassium iodide solution, sodium molybdate in sulphuric acid (Frohde). potassium-bismuth iodide aud potassium-mercuric iodide. The presence of meconic acid and of alkaloids being demonstrated, it became evident that we were dealing with poisoning by opium.

Lee Hee is supposed to have taken the opium at about 10 a. m., and the quantity taken we estimated to be at least ten grams, judging from the amount that still remained in the little jar which was known to have- been full when the suicide was attempted.

About half-past five Lee Hee was brought into one of Prof. Osier's wards in a comatose condition and it was evident from the state of his respiration and circulation that he was not likely to recover. At this time the stomach was first washed out and the process was repeated until the physicians in charge

• UnterHUchungen zur acuten u. cbroniscben Morpliinvergiftung.

Deutsche Meil. Wochenschr., 1883, nr. 14.

t Ueber Elimination stibciitan applicirter .\rzneimittel durch die Magensclileimliaiit. Inang. Dissert. Gottingen, 188H.

t Unteraucliungen iiber die .\us8clieidung des Bubcutan injicirten Morpliins dnrcb den Mai;en. Herl. Klin. Wochenscbr., 1889, nr. 25.

g Arcb. f. exp. Path. u. Pbarmakol., Bd. 27, S. 330.

had reason to think that there was no longer any opium in the stomach. A second lavage was made at 8 p. m., aud a third at half-past eleven, a quarter of an hour before death. The fluid secured in these last two washings was colorless and frou) this fact it may be concluded that all the crude opium had been removed by the first washing, though unfortunately this conclusion could not receive positive proof, since the last portion of the first washing was not kept separate from the rest and chemically examined. All three washings were examined for ojjium and morphine and the results, which will presently be given, at least demonstrate the practical value of repeated stomach washings, even after all ordinary signs of opium, such as color and odor, are no longer found.

At G p. m., 75 cc. of urine was removed by the catheter and submitted to a chemical examiqatiou by Landsberg's method for the detectiou of morphine in the urine.* The residue finally obtained was a mixture of ui'ea and morphine. Xo difficulty wa^experienced in identifying the former, it appeared in the characteristic four-sided prisms with pyramidal ends. Tn addition to these ci'vstals of urea there were seen numerous very small rhombic prisms. Whether the latter were certainly crystals of morphine was not determined; nevertheless the chemical tests demonstrated the presence of morphine in considerable amount. This difficulty in separating morphine from urea is not peculiar to this case,! but is due to the fact that both behave toward solvents in much the same way. Control tests showed that urea does not interfere with the following morphine reactions. A minute quantity of the residue dissolved in water and treated on a porcelain dish with a drop of ammonium molybdate, gave a yellow precipitate, and the addition of a drop or two of concentrated sulphuric acid caused that beautiful play of colors, violet, blue and green, which solutions of morphine give under the same conditions (Frohde). A fragment of iodic acid added to the <liluted residue was reduced and the free iodine recognized by shaking with chloroform. In this way the presence of morphine in the urine was demonstrated. In the present case, therefore, there was no difficulty in proving the elimination of at least a part of the ingested alkaloid through the urine. Yet there is probably no point in the physiological history of morphine which has given rise to more controversy than its presence or absence in this excretion. The controversy involves not only the immediate experimental results but the more general problem of the fate of morphine in the body. Thus, some observers after demonstrating that the alkaloid was present in the urine claimed that it passed through the body unchanged; others, failing to find it, argued that it suffered a destructive oxidation and could not be demonstrated as mor

• Pfluger's Archiv, Bd. 23, S 425 (1880).

tNeubauer u. Vogcl, Analyse des Hams, Th. 1, S. 359.

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

95

pliiue in the urine. But it is now generally admitted that after large doses of the alkaloid a small quantity appears in the urine.

It is in the stomach, however, that the elimination of morphine proceeds most actively. The practical importance of this gastric excretion will be evident upon considering the results of the stomach washings in the present case.

Of these there were three as already mentioned. The first was the sherry-red fluid giving meconic acid reactions, and upon treatment by the method of Stas, alkaloidal reactions. This fluid was treated like the urine and a similar brown residue was obtained. This residue was dissolved in water, acidulated with hydrochloric acid and again evaporated. During this evaporation a white precipitate separated out which upon examination was found to be calcium phosphate, one of the inorganic constituents of opium. Having removed this salt, the residue was dissolved in warm absolute alcohol and allowed to evaporate spontaneously. Morphine crystals of a definite type were not obtained, but the solution gave beautiful morphine reactions ; reducing iodic acid, responding to Frohde's reagent, and giving a pink color with sulphuric and nitric acids (Husemann).

As already stated, it was believed that all the opium was removed during the first washing, and the fact that the second washing came out colorless seems to confirm this view. Nevertheless the latter liquid gave fine alkaloidal reactions, but did not respond to the tests for meconic acid. In other words, at the first washing the ingested but unabsorbed opium was removed; between this first lavage and the second the alkaloids had accumulated again. How ? It could only have been through an excretion by the gastric mucous membrane. Nor did the elimination of the poison stop at this period ; for, the third washing made several hours later, colorless also, still gave good reactions.

The meaning of these results must be clear. They point to the excretion of the alkaloids of opium by the mucous membrane of the stomach and suggest a practical application of this fact. If, as has been shown, these alkaloids, and morphine in particular, are excreted into the stomach, then washing this viscus repeatedly and at very short intervals to remove the alkaloids as fast as they are eliminated, must certainly be a life-saving process whether the poison has been taken by mouth or hypodermically. Poisoning by the latter method

has not, as far as can be ascertained, been treated in this manner in spite of Alt's demonstration of the presence of morphine in the stomach washings of men who had received 3 eg. of the hydrochlorate subcutaneously. The quantity of the alkaloid capable of being removed by repeated washings has beeu estimated at almost one-half. Tauber also recovered 41.3 per cent, from the faeces of dogs to whom morphine was administered subcutaneously but where the stomach had not been washed out. Alt has ascertained that for dogs, doses of more than 10-12 eg. morphine pro kilo may be considered lethal; 17 eg. pro kilo almost invariably caused death. On the other hand, if, immediately after the injection, the stomach was washed and the lavage continued for forty-five minutes, then 10-13 eg. pro kilo never produced serious symptoms, and indeed with ] 7 eg. and even 20 eg. pro kilo the symptoms of poisoning were not so severe as when 12 eg. were administered without repeated washing. Two dogs were saved after the injection of so large a quantity as 24 eg. pro kilo. This evidence goes to prove that the excreted morphine is reabsorbed and that it still has toxic properties ; and may not the frequent relapses following ajiparent recoveries from overdoses of morphine* also furnish proof of such reabsorptiou 't By a continuous lavage the exchange that goes on between the gastrointestinal mucous membrane and the general system would be interrupted, and in proportion as the alkaloids excreted by the mucous membrane are removed the effects of their reabsorptiou would be avoided. Conformably to the results of Alt's experiments, the lavage should be repeated at short intervals, and the sooner this can be done after the opium or morphine has been taken, the better. In the case cited in this paper no successful outcome could be anticipated, because too long a time elapsed between the talking of the opium and the beginning of the treatment.

In connection with this subject it may be well to repeat Kobert'sf suggestion', that a chemical examination of the faeces should be made in cases where the morphine habit is suspected but is denied by the patient, and where for various reasons it is difficult to secure conclusive evidence of the fact in other ways.

•See for example, Souclion : "On relapses following recoveries from overdoses of injections of morphine," N. Orl. JI. & S. J., XIV, pp. -ir.T-oO, 1886-S7 ; Taylor : " Lancet," Vol. I, p. 937 (1884).

f Lehrbucli der Intoxikationeii, p. 5(U.

DEATH OF JAMES CAREY, TRUSTEE OF THE JOHNS HOPKIXS HOSPITAL

Minute adopted by tiik Hoard of Tki'stkks of The Trustees of the Johns Hopkins Hospital, having learned with deep sorrow of the sudden death of J.vmes Carey, one of its most faithful and conscientious members, desire to put upon permanent record their appreciation of his character and services. He was the soul of integrity and uprightness iu every relation in life. His heart was full of sympathy for the sick, the sorrowing and the unfortunate. It can be said of him ihat he wronged no man iu thought, word or deetl, but was kind ;itul helpful to all. lie had no enemies, but many I'lieuds. lie ki\ed chilihrn, and was tender and gentle with

THK .Toiixs HoPKiKS Hospital. October 0, 1804. them to a remarkable degree. He took great interest iu the Johns Hopkins Colored Orphan Asylum and was eager to develop a better work in the new buildings in course of erection. At the last meeting of the Trustees he attt^uded he was iu full sympathy with new plans for the care and training of colored orphans. He was also peculiarly interested in all the humanitarian aims and work of the Hospital, and bis sound judgment and wise counsel commanded the highest resjHH^t of his associates. After a pure life, full of good deeds and kindly impulses, he hsis gone to his reward.

96

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 42.

THE BACILLUS OF THE PLAGUE.*

ABSTEACT OF REPORT TO THE .JOURNAL CLUB OF THE .JOHNS HOPKINS HOSPITAL.

The epidemic of the black plague which broke out in May last in IIong-Kong and was very destructive to the Chinese population, will be nuxde memorable in the history of modern medicine on account of the simultaneous discovery by a French and a. Japanese investigator of the micro-organism which there is reason to believe is the cause of the disease. These two investigators, who are already well known to the scientific world through their important previous contributions to the literature of bacteriology, are Drs. Yersin and Kitasato.

The former, Dr. Yersin, who was sent by the French government, owing to the danger to their Indo-Chinese possessions, with instructions to study the nature of the plague, the conditions under which it is propagated, and to search for more effective means for preventing the invasion of their possessions, arrived in Hong-Kong on June 15th.

Dr. Kitasato, accompanied by Dr. Aoyama, was sent by the Japanese government, and arrived at Hong-Kong on June 12th. Dr. Aoyama was delegated to study the clinical and pathological features of the disease, whereas Dr. Kitasato was to undertake the investigation into its aetiology. Dr. Aoyama became infected with the disease, but recovered. Hence tho report of their investigations relates quite exclusively to the bacteriology of the disease.

On June 14th the first autopsy was conducted by Dr. Aoyama, and the blood and organs were studied for microorganisms by Dr. Kitasato, who at the same time made cultures. Under the microscope bacilli were found in the cover-slips, but as the individual had been dead 11 hours the result was not considered conclusive. However, guinea-pigs were inoculated with a bit of the spleen and the blood from tho case.

On the same day, in the blood taken from the tip of the finger of patients sick of the disease, bacilli agreeing in form with those found at the autopsy were again met with. The next day (June 1.5th) the blood-serum cultures nuulc from the autopsy of the previous day showed upon examination a growth of micro-organisms which resembled the bacilli already seen. From these cultures a guinea-pig, mouse, rabbit and pigeon were inoculated.

The guinea-pigs inoculated from the spleen and the blood of the patient dead of the disease, were dead on the second day, and the autopsy U2)on tliese animals showed oedema at the seat

•The importance of the discovery of the micro-org.anism believed to be the cause of the idague seems to justify tlie publication of abstracts of tlie two original pajjcrs wliicli have just appeared on the Biihjcct. Moreover, as one of tliem (Kilasato's) appeared originally in Japanese and is therefore relatively inaccessible to English readers, it seemn less necessary to apologize for presenting the results together at this time. This it would have heen impossible for me to do hut for the kindness of Dr. S. H. Sanobe, now attending u))on the post-graduate courses at the Johns Hopkins Hospital, who kindly read the Japanese jiajier to me. The two riapers are to be founil in the .Sei-i-Kwoi (Medical Journal), TOkyo, for Sept. 8, 1894, and Le Bnlletin Medical, Sept. 23, 1894. In the latter a French abstract of the report of Dr. Kitasato is also given. — Simon Flbxmeu.

of inoculation, and the bacilli were recovered from the viscera of the animals. Of the animals inoculated with the growth from the serum-cultures, all died, in from 1 to 4 days, according to the size of the animal, excepting the pigeon. The latter survived. The post-mortem examinations of these animals confirmed the conditions observed in the first experimental guinea-pigs.

Kitasato found the blood of human beings, dead of the plague, to contain the bacilli often in such small numbers that in many preparations perhaps not more than 2 or 3 organisms could be found ; while the lymph glands, spleen, liver, lungs, brain and intestines always showed many bacilli, which could be cultivated. At times in cover-slips made from the inguinal glands and spleen the number of organisms was so great as to suggest that they had been made from a culture. In all the inoculations from the organs a single organism in pure culture was invariably obtained.

The characters of the bacillus. — The micro-organism obtained in all instances consists of short rods, with rounded ends, resembling the bacillus of chicken cholera, and possessing a capsule. This capsule is at times quite distinctly marked, at others it is difficult to see. The bacillus stains in aniline dyes, the ends staining mor deeply than the middle portion. According to Yersin it is decolorized by Gram's staining method. It is described by Kitasato as being very motile.

Upon blood-serum, after 34 to 48 hours, at the body temperature, the bacillus grows abundantly, the growth appearing moist and of a yellowish-gray color. No liquefaction of the blood-serum occurs. It also grows upon agar, but better upon glyceriue-agar, forming a grayish-white surface growth. The colonies in agar plates show a bluish translucence. They are round, or present slightly irregular contours, and are moist in texture. The young colonies are glass-like in apjjearance, but in the older ones the central part becomes thicker and more opaque. In bouillon, according to Kitasato, a cloud is produced, whereas Yersin compares the growth in this medium with the appearance produced by the streptococcus erysipelatos, namely, the fornuxtion of small granules which settle upon the sides and to the bottom of the test-tube. Stab cultures show after 1 to 2 days a fine dust-like line of growth. The bacillus does not grow on potato, in 10 days, at the ordinary temperature, but after two days at the temj)erature of 37.5° 0. a growth, gray in color and with a dry surface, was observed. The mean temperature of Hong-Kong was too high to permit of gelatine being used.

The most favorable temperature for the growth of the bacillus seems to be from 36° C. to 39° C. According to Kitasato, it docs not form spores. Cover-slip preparations from young agar-agar cultures show forms resembling chains of cocci, but older ones present distinct bacillary forms.

Effects upon animals. — The animals used for experiments were those previously mentioned, namely, rabbits, guinea-pigs, rats, mice and pigeons, and in Kitasato's experiments, sheep. With the exception of jtiiicous, all tlu'.se aiiinials jtroved to be

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

97

susceptible. The symptoms of the disease developed in the inoculated animals from the first to the fourth day, depending upon the size of the animals. According to Kitasato, the animals are uniformly small at Hong-Kong, the average weight of guinea-pigs being 115, and of rabbits 200 to 250 grams.

The first effects of the subcutaneous inoculation were already perceptible in Yersin's cases after a few hours. The seat of inoculation became oedematous, and the adjacent lymphglands could be felt. After 24 hours the animal is quiet, the hair is rumpled, tears run from the eyes, later convulsions set in which usually continue until death occurs. At the seat of inoculation there is hemorrhagic cedema, the lymphglands are swollen, the intestine is sometimes hyperiemic, the adrenal glands congested, the kidneys purple, the liver large and congested, and the spleen is much enlarged, showing, at times, according to Yersin, £to eruption of miliary tuberclelike nodules. The bacilli can be recovered from the organs of the experimental animals.

In this connection it is interesting to note that in the i^art of the city where the disease prevailed many rats were found lying dead upon the ground and in the houses of the diseased; and it is stated by Yersin that in the epidemics of Pakhoi and of Lien-Chu, in the province of Canton, it had been observed that before the plague attacked human beings it raged with great intensity among mice, rats and swine.

Hahital of the hacillus. — It has already been mentioned that the blood and organs of human beings and experimental animals dead of the plague contain the bacillus. The same organism has been obtained from the rats found dead in the infected district, and Yersin having observed that the flies which infested the laboratory in which his autopsies on experimental animals had been conducted were dying in large numbers, found on making cultures from one that it contained the organism. Kitasato inoculated three guinea-pigs with the dust derived from the room in which there was a case of the plague. Of these two died of tetanus ; the remaining one died with the symptoms of the plague, and the bacillus was obtained from the internal organs. Yersin obtained earth at a distance of 4 to 5 centimeters below the surface from the soil of an infected house. From this cultures wei"e made, and bacilli having the cultural properties and the form of the plague bacillus were isolated. These were, however, devoid of virulence.

Yersin pointed out in a previous part of his paper tliat in cultures from the glands or the blood the colonies grow with different degrees of rapidity, and the more rapidly growing ones are less virulent than the slower ones. Thus the growth derived from a particular colony might kill guinea-pigs after a longer period of incubation, or not at all, and yet be fatal to mice. He also obtained from a gland which had been removed in the third week of the disease, a culture of the organism which was destitute of pathogenic pro})erties, even for mice.

Healthy mice placed in tlie same; cage with inoeulaied mice succumb to the disease, aUliougli later than the infected ones; and susceptible animals fed with food containing the bacillus may die and present the characteristic lesions.

Action of physical and chemical agents on tJie mtalily of the hacillus. — These experiments were conducted by Kitasato.

a) Physical. — 1st. Drying. Cover-slips were made from the infected lymph-gland, and exposed in a room having a temperature of 28° to 30" C, being protected from sunlight. These were dropped into bouillon at varying periods. Those exposed from 1 to 36 hours gave a growth when kept in the thermostat for two days, while cover-slips which had been exjjosed for four days gave no growth in bouillon at the end of seven days in the thermostat. — 2d. Sunlight. Cover-slips prepared in the described manner failed to give any growth whatever after an exposure to the direct rays of the sun for 3 to 4 hours. The experiments were repeated with a pure culture of the bacillus made upon blood-serum with the same results. — 3d. Heat. Bouillon-cultures were killed in § hour at 80° C. In steam at 100° C. all the organisms were killed in a few minutes.

b) Chemical. — 1st. Carbolic acid. Three-day old bouillon cultures were treated with quantities of carbolic acid equaling 0.5 per cent., 0.75 per cent, and 1.0 per cent, of their volume. From these mixtures inoculations were made into fresh bouillon every few minutes.

0.5 per cent, carbolic acid. After one hour's contact at room temperature, a growth in two days at temperature of the thermostat.

0.75 per cent, carbolic acid. Same result.

1.0 per cent, carbolic acid. After one hour's contact no growth in one week at 37.5° C.

0.5 per cent, carbolic acid. After two hours' contact at room temperature, no growth in one week at 37.5° C.

2nd. Milk of lime. The same plan was pursued, using the solutions of the same strength.

0.5 per cent, milk of lime. After 2 hours' contact a very slight growth.

0.5 per cent, milk of lime. After 3 hours' contact no growth.

1.0 per cent, milk of lime. After 2 hours' contact no growth.

Symptoms of the disease. — The disease comes on suddenly after an incubation period of 3 to G days. There is great lassitude and prostration. The temperature rises, and delirium may be present. In 75 jjer cent, of the cases the glands of the groin become swollen, in 10 per cent, those of the axilla, and rarely those of the neck and other regions. The tongue is heavily coated and black in color. Vomiting and diarrhoea may occur, and are considered as being very unfavorable. Death may occur in 48 hours, and frequently it takes place sooner. Should the patient live until the 5th or 6th da}' the prognosis is better. The enlarged glands may go on to suppuration and the abscesses so formed heal very slowly. The disease attacks males and females, the old and the young. The mortality in this epidemic is given by Kitasato as 75 to 85 per cent., by Yersin as 05 per cent,

Kitasato examined the blood of 30 cases, 25 of which gave positive results. Of the remaining five, two were proven not to have the disease; the remaining three were doubtful. The organisms are difficult to see in cover-slips from the blood ; it is therefore necessary to make cultures.

The conclusions which are ap^wuded to Dr. Kitiisato's report are as follows :

98

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 42.

1. In the plague, bacilli are found in the blood, glands and viscera.

3. Tills particular bacillus is not found in any other disease.

3. Obtained in pure culture it is capable of producing in inoculated animals the same effects as in human beings.

4. It gains entrance into the body through (a) the respiratory tract, (b) excoriations of the surface, (c) the digestive tract.

5. The disease prevails especially under faulty hygienic conditions; it is therefore urged that general hygienic measures be carried out. Proper receptacles for sewage should be provided ; a pure water supply afforded ; houses and streams are to be cleansed; all persons sick of the disease isolated ; the

furniture of the sick washed with a 2-per cent, carbolic acid solution in milk of lime; old clothes and bedding are to be steamed at 100° C. for at least 1 hour, or exposed for a few hours to sunlight. If feasible, all infected articles should be burned. The evacuations of the sick are to be mixed with milk of lime; and those who die of the disease are to be buried at a depth of 3 metres, or, pi-eferably, cremated. After recovery the patient is to be kept in isolation at least one month. In one case he was able to demonstrate bacilli in the blood after the third week. All contact with the sick is to be avoided, and great care is to be exercised with reference to food and drink.

PROCEEDINGS OF SOCIETIES,

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of May 7, 1894 {continued).

Dr. Kelly in the Chair.

Report of Twelve Cases of Complete Radical Cure of Hernia, by Halstcd's method, of over two years standing:. Silver wire sntnres. — Du. Halstkd.

Dr. Bloodgood has very kindly written to all of the old hernia cases in town and to several living out of town, requesting them to come to show themselves to-night. It is now nearly five years tliat we have done this operation for the radical cure of hernia. You may remember that a little more than a year ago we reported 89 cases of hernia, and that there were no recurrences in the cases of union by first intention. In G cases there was more or less of a recurrence, but all of these cases had suppurated for some reason or other, and had liealed by granulation. It remains to be seen wh&ther or not there are any returns amongst the cases here tonight.

This first man v/as operated upon only two weeks ago to-day. In this case and other recent cases we have used silver suluies instead of silk, not because we wish anything stronger than silk, l)ut because of the results of experiments which Dr. Bolton has kindly made for us, and which we liave made, to determine the |iower of different metals to inhibit tlio growth of bacteria. This line of exjicrimentation is not entirely original with us. Dr. Bolton has found that zinc and cadmium and copper are perhaps the best metals to inhibit tiie growth of organisms. Silver is perhaps the next best metal, and we are using therefore silver wire altogether, botli for deep buried sutures and for the continuous Ijuried skin sutures. This is a beautiful instance of healing by first intention.

Since my last report of a year ago we liave Iiad a groat many cases of hernia, and so far tliere have been, we believe, no recurrences.

OLD CASES OF HERNIA EXHIBITED AT THE MEDICAL SOCIETY.

Case 1. J. B., let. 48. Had a very large right, oblique, inguinoscrotal, reducible hernia of fifteen years standing. Operation in August, 1889 (four years and six months ago). The bladder was caught in one of the stitclies, and tlie wound consequently was laid open and allowe<l to Ileal by granulation. The scar now is firm, <lepressed, 12i cm. long, and about 1 cm. in width, there is no impulse on coughing, no change in the cord or testicles, the man Buffers no inconvenience from the wound.

Case 2. F. F., a;t. 7 (boy). Small, right, congenital, inguinal, reducible hernia. Operation in October, 1889 (four years and four months ago). Wound healed per primam ; there is a narrow linear scar, no impulse on coughing, no change in cord or testicles, no discomfort from wound.

Case 3. H. S., set. 37 (colored). Large, right, inguinal, reducible hernia of two years duration. Operation February, 1890 (four years ago). Healed per primam ; there is a narrow linear scar 9 cm. long, firm, no impulse, the little finger can detect the opening in the muscle through which the transplanted cord passes, no inconvenience from wound, no change in cord or testicles. Patient does heavy work.

Case 4. E. P., ret. 7 (girl). Small, right, oblique, inguinal, reducible hernia of two months duration. Operation November, 1S90 (three years and four months ago). Healed per primam, except a small superficial stitch abscess, the scar is white, 11 cm. long and about 4 cm. wide, firm, no impulse, no discomfort.

Case 5. A. E., set. 5. Small, right, oblique, inguinal, reducible hernia of four years duration. Operation by Dr. Brock way (McBurney's method) in July, 1890. The hernia recurred, and in November, 1890 (three and one-half months afterward), a second operation by Halsted's method was performed. The wound healed per primam, notwithstanding the fact that the child had whooping-cough. It is now three years and three months since the last operation, and there is no return of the hernia.

Case 6. F. S., £et. 27. Small, left oblique, inguinal, reducible hernia of two months duration, following typhoid fever. Operation February, 1891. Healing per primam, except for a small superficial stitch abscess. It is now three years since the operation. The scar is firm, white, 12 cm. long. There is no imjiulse on coughing. No discomfort. Testicles and cords normal.

Case 7. J. T., ret. 47. Small, right, oblique, inguinal,-reducible hernia of six weeks duration. Ojieration February, 1891 (three years ago). Healed per ])rimam. The scar is narrow and white, 13 cm. long, firm. No impulse on coughing. No discomfort. Testicles and cords normal.

Case 8. W. C. W., set. 2*. Small, right, inguino-scrotal, congenital, reducible hernia. Operation July, 1891 (two years and eight months ago). Scar wdiite, linear, 8 cm. long, firm. No impulse on coughing. No change in cord or testicle.

Case 9. G. B., ict. 22. Right, oblique, inguino-scrotal, reducible hernia, noticed at birth ; wore a truss from eight to thirteen years old. Operation August, 1891 (two years and seven months ago). The scar is 13 mm. wide and 12 cm. long, white, firm. No discomfort. On coughing there is a slight impulse at the lower en<l of the scar just above the pubes, corresponding to the external ring. There is no return of the hernia..

Case 10. A. McI., a;t. 26 (colored). Right, oblique, inguino-scrotal hernia, reducible for four years, strangulated on admission. Operation August, 1891 (two years and seven months ago). The veins were very large and excised, healing per primam, exce)it at the upper end, in which there was superficial suppuration, November, 1893. Hydrocele and testicle, on the same side, removed

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because they gave discomfort. Tlie .scar is firm, there is no impulse on cou<;hing. No discomfort.

Case 11. J. W. B., vl'I. 5. Small, left, oblique, inguino. reducible hernia, following whooping-cough at four months of age. Operation September, 1891 (two years and five months ago). The wound suppurated at its upper third and healed by granulation. The scar is 2 mm. wide, it has stretched some. Is 8 cm. long and firm. No impulse on coughing. Testicle and cord normal. There had been an epididymitis following the operation, the induration from which lasted for six months.

Case 12. H. P., aet. 29. Small, right, inguinal, irreducible hernia of two years duration. Operation October, 1891 (two years and five months ago). There were no adhesions in the sac. Wound suppurated and healeil by granulation. There was a stitch sinus for three months. The scar is firm, but has stretched a little. It is 11 J cm. long. The abdominal walls of this patient are so very thin that on coughing there is an impulse above Poupart's ligament on both sides. The impulse is as great on one side as on the other.

Recent Results in Hysteromyomectomy.— Dk. Kelly.

The technique of no operation in the field of gynecology has been so rapidly advanced as that of hysteromyomectomy. Until a few years ago the removal of a myomatous uterus was considered one of the most dangerous operations, and was only resorted to wheu the patient's life was in imminent danger from the further growth of the tumor or from the secondary results such as high grade ansemia, pressure from adjacent organs, etc.

Less than twenty years ago the first attempts at the extirpation of these myomatous uteri were made, and the mortality following these operations was so appalling as to cause all but a few to shrink from the operation.

Some ten years ago, Professor Scliroeder, of Berlin, with the courage of his convictions, began with great earnestness to advocate the total extirpation of myomatous tumors, and although his attempts were followed by a very high rate of mortality he persisted, believing that better results would follow as the steps of the operation were perfected. These anticipations were not realized during his life, but in the light of the statistics of to-day his prophecy for the future is well sustained. At the present time the mortality following this operation is little if any greater than that following the average run of ovariotomies.

We now consider the operation indicated when the tumor is rapidly growing even though no uncomfortable symptoms are produced by its presence, as sooner or later, in the great majority of cases, untoward symptoms will arise which not only endanger the patient's life, but also render the operation in the presence of these complications much more difficult.

As will be seen from the analysis of 50 cases of hysteromyomectomy, made for me by Dr. Clark, there are quite a number of indications for operation.

From the standpoint of relative frequency of myoma in the white and colored race this analysis of 50 cases, while small in number, yet serves to bear out a statement made by me some months ago before the South Carolina Medical Society, that myomata were as frequent in white as in black women.

A number of those present at that meeting took exception to this remark, claiming that white women were able, being better situated financially, to come greater distances for treatment than were the impoverished colored women who, perforce of circumstances, must remain at home.

But according to the relative frequency as indicated by this table the proportion is as 61 to 1, there being 43 whites to 7 blacks. Of the latter G appeared to be of pure African descent, the seventh was a mulatto.

While the criticism olTered l)y these gentlemen bears a certain weight, yet from the very fact that we are in the center of a large negro population in Maryland aud the adjacent States of Virginia

and Delaware, the proportion should be very different from this which I present, if the statement that myomata are more frequent in the colored than in the white race is to be sustained.

The ages of the patients at time of the operation averaged 42.5 years, the oldest being 59 and the youngest 25 years of age.

This part of the analysis is interesting as showing the prevalence both among physicians and laity of the belief that these tumors will disappear or cease to give rise to discomfort after the menopause.

In a number of these cases the tumor had been discovered two or three years, in a few instances many years before the operation, the patients having delayed operation in the hope that the menopause would relieve them.

Although the above opinion is still held by many worthy gynecologists I give it little credence, as according to my experience, instead of decreasing in size, a number of these tumors take on their most active growth after the menopause, while in many other cases the menopause is delayed five years or longer by their presence.

Continuing the analysis further, I find that 37 of the women were married and thirteen single. Of the former, twenty-three bore fifty-six children. Seventeen miscarriages occurred among this number ; one patient, however, furnishing ten of these, the remaining seven being distributed among the 22 other women.

The prevailing belief is that these women are as a rule sterile. In the great majority of these cases which I report no children had been borne after the tumor had attained a great size, but on the average the fertility of these women was little below normal.

The following data relating to the menstrual (low bear out the usual statement, namely, that there is deranged menstruation, usually tending to profuse and irregular flow. Of the 50 cases, 9 were normal as to menstrual function ; in 35 the How was excessive, often inclined to free or profuse hemorrhage ; while 5 had passed the climacteric.

The major indications for operation were increasing size of tumor, secondary anaemia from persistent or profuse hemorrhage, and pressure symptoms ; of the 50 cases, 30 presenting tliis group of symptoms. In two cases excessive hemorrhage alone was the indication ; in four, rapidly increasing size of tumor, although accompanied by no unpleasant symptoms ; in five, severe pain. Another indication is the urgent request of a patient to be relieved of her tumor. In such cases I usually advise the patient to wait a certain length of time, usually from six months to one year, and if she is then still urgent in her request I will operate. Two cases in this list were of this character. In one case there was profound mental dejiression, verging closely on to melancholia, caused by constantly brooding over the fact that she had "a tumor." Operation was followed promptly by complete restoration of the patient's spirits.

In one case the tumor was not detected until pregnancy was six months advanced, and then it so blocked the inferior strait as to require Caesarean section for the delivery of the child. In this case the uterus was amputated and the pedicle dropped and the abdomen closed as in the ordinary hysteromyomectomy.

Of the remaining 50, one was the subject of an intense pruritus vulva?, from constant discharge ; another, of prolapsus uteri, and a third had attacks of urinary suppression, while two had peritonitis.

Although myomatous tumors are often thought to be unaccompanied by pain, yet my analysis shows that of the 50 cases, 21 complained of pain of varying intensity, from a heavy dragging sensation in the pelvis to acute pain in the region of the uterus or ovaries, often resembling " toothache." A considerable proportion referred their pains to the legs and groins, evidently due to pressure on the sacral and lumbar plexuses.

A complication not infrequently associated with these tumors is infiammatory disease of the appendages, v.irying in degree from slight adhesions to purulent salpingitis. In this list which I present one such case is found. The presence of pus necessarily renders the operation more dangerous, as the liability to infection

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is very greatly increased. In a second case there was a pyometra, the pas escaping into the pelvis when tlie uterus was amputated. I'liis i>atient, however, made an uncomplicated recovery. As a precaution against the general distribution of the pus the stump was surrounded by pads of gauze, and at the completion of the operation, before closing the abdomen, the pelvis was thoroughly irrigated with salt solution.

A few words as to the evolution of hysteromyomectomy.

The first mode of operation systematically described and generally adopted was that of Hegar.

According to his method the abdomen was opened, the tumor lifted out, a rubber ligature thrown around the pedicle, the uterus amputated, and the pedicle suspended in the abdominal wound by means of pins. The stump was dressed for two weeks or longer until it gradually separated, leaving a granulating pit in the bottom of the wound. Schroeder soon modified this method by dropping the stump, but his operations were followed by such a high rate of mortality as to prevent the general adoption of this operation.

After having followed Hegar's method in two cases, in Philadelphia, I devised a new operation, which I described as the combined extra- and intraperitoneal method. This included the best principles of Hegar's and Schroeder's methods. Hemorrhage frequently arose from the slipping of the constricting ligature in the Hegar operation. The pedicle was often large, and the encircling ligature, although controlling the hemorrhage during the operation, would subsequently slip after the disappearance of the temporary oidema, and fatal bleeding would follow. This no doubt was the cause of death in manj' cases.

Schroeder, as did the general surgical world, assigned his high rate of mortality to two causes — sepsis and hemorrhage.

It was accepted without question that the sepsis came from the cervical canal. I was convinced of this fact, and only conducted the first part of my operation according to the plan of Schroeder.

After amputating the tumor I carefully approximated the cervical stump, leaving the sutures long, by means of which I drew the stump up into the lower angle of the abdominal wound, and detained it there by catching the ligatures with artery forceps.

I then attached the peritoneum to tlie stump on all sides, and closed the abdomen down to the lower angle. Without exception these cases did well, and the wound filled in nicely with granulation tissue.

After having employed this method satisfactorily in a great many cases, I decided to drop the stump completely into the abdominal cavity as one does the pedicle of an ovarian tumor. <

Since adopting this method 1 have performed 50 operations, with only three deaths, the latter being in no way traceable to infection from the stump.

One death was due to septic catgut, another to shock, and the third to sepsis which arose from a superficial eczematous patch in the fold of the abdomen. This patch was protected by a sealed dressing, but during the operation it became displaced. There was extensive infection of the abdominal wound in this case, the peritoneal cavity being free of pus.

Looking back at Schroeder's high rate of mortality we can arrive at but one conclusion, and that is that his antiseptic precautions were not sufDcient.

I am now quite certain that a healthy cervical canal does not give rise to infection in these operations.

With regard to hemorrhage, there is little danger if the ligatures are properly placed. There are but four great channels of blood supply to these tumors, regardless of their size, be they large or small, the two ovarian and two uterine arteries.

The two ovarian arteries can be caught easily above and tied off. riie accompanying veins are fre<iuently enormously enlarged, and care must be ob.served not to i>rick them with the needle, as embarrassing liumorrhaKo will follow such an accident.

These vessels should bo tieil also on the uterine side, and cut

between the ligatures, thus preventing the blood which remains in the tumor from running down and obscuring the field of operation. Having secured this source of licmorrhage, the broad ligaments are opened, and by dissecting down between their layers with the finger the uterine arteries, the remaining sources of blood supply, are felt beneath the finger on the floor of the pelvis. If these are firmly ligated there is no necessity of throwing a provisional rubber ligature around the base of the tumor while it is being amputated.

The tumor is removed by a circular incision, the vesical peritoneum being first dissected off, as it will be used later to form a hood for the stump. The pedicle is cupped, and with three or four silk sutures of medium size (No. 2) the surfaces of the flaps are brought into apposition. The edges usually require two or three sutures to complete a snug approximation. The redundant peritoneum is then brought together with a continuous silk suture (No. 2), and the female pelvis is converted into one of the male type, all of the structures between the rectum and bladder having been removed.

From the analysis of 50 cases it will be seen that the operation for the total extirpation of myomatous uteri is eminently successful, and w hen a case presents any of the indications enumerated above should be operated upon.

Summary of 50 Cases of HysTEROMyoMECTOMy.

Age. — Youngest, 25 years; oldest, 59 years; average, 42.5 years. 29 of the 50 cases between the ages of 40 and 50.

Married. — 37.

Single. —13.

Color. — 6 blacks ; 1 mulatto ; 43 whites.

Children. — 13 married were sterile ; 23 married women gave birth to 56 children.

Miscarriages. — 17 miscarriages occurred, one patient furnishing 10 of these, leaving only 7 to the remaining 22 married women.

Menstrual history. — Menses normal, 9 cases ; menses profuse, often inclined to free or continuous hemorrhage, 36 cases ; climacteric, 5 cases.

Indications for Operation. — Profuse hemorrhage, increasing size of tumor, secondary aniemia, and pressure symptoms, 30 cases ; excessive hemorrhage, 2 cases; increasing size of tumor, 4 cases; pain, 5 cases ; urgent request of patient, 2 cases ; mental depression caused by presence of tumor, 1 case; myoma blocking inferior strait, preventing delivery of child, 1 case : suppression of urine,

1 case ; intense pruritis, 1 case ; prolapsus uteri, 1 case ; peritonitis,

2 cases.

Of the 50 cases, 23 complained of pain, frequently quite severe, in the region of the tumor. Drainage.— Gsmze, G cases ; no drainage, 44 cases. Stitch-hole abscess. — i cases. Mortality. — 6 per cent.*

• Since reporting these cases before the Johns Hopkins Medical Society I have completed my seventieth operation without any increase in the mortnllty.

THE JOHNS HOPKINS HOSPITAL REPORTS.

KEPOllT IN GYTNECOLOGY.

By HOWARD A. KELLY, M. D.,

Professor of Oynccology in the Johns Haitians UnivcrHty and Gynecologist to the Johns Hophins Hospital.

This report containing 460 pages, large octavo, and G3 plates and figures, is now ready. It includes many papers of interest and importance to gynecologists. Price $3.00. Price of Vol. 3 complete, $5.00.

October, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

101

NOTES ON NEW BOOKS.

Burdett's Hospital and Charities Annual, 1894 : being the Year-book of Pbilantbropy. Edited by Henry C. Burdett, Author of "Hospitals and Asylums," etc. {London: The Scientific Press (Limited). New York: G. Scrihiier & Sons.)

One hardly knows which to admire most, the patience displayed in collecting the immense store of statistical information contained in this volume of more than 500 pages, or the skill shown in marshaling and handling the facts to bring about better hospital administration. The book is a marvel of laborious compilation : how great the labor few can realize who have not had a similar task in wringing statistics from indifferent, over-worked or procrastinating public officials. Many of the statistics are of purely local interest, and many of the topics referred to have special bearing upon the English hospitals and training schools for nurses, but the book, as a whole, is proiitable to hospital workers throughout the world.

Among them may be mentioned such subjects as the training of nurses in mental cases, hospitals for consumption, homes for the dying, and hospital finances. The author, with a prescience born of long experience, has touched a vital point of hospital administration in his chapter on hospital finances. As he so clearly points out, it is only by a comparison of the figures presented by each hospital that we can accurately determine what good is being accomiilished and whether money is judiciously expended.

It is safe to say that those hospitals alone will endure which are able by the results attained to show a reason for their existence. The author had previously presented in another little volume, "A Uniform System of Accounts for Hospitals and Public Institutions," a scheme of classification of expenditures which in his judgment should be generally adopted, and the figures presented in the Annual" indicate that gratifying progress has been made in securing the adoption of the scheme in England. It is very desirable that some corresponding although probably not identical scheme should be adopted in America, as the conditions of our hospitals, while varying somewhat in details, are essentially the same. In some respects they could be improved. The unit of expenditure should be one day instead of one week, for example, and the cost of maintenance should be reckoned upon the actual number o/Ai^s of hospital care given, and not upon the weekly cost of the average number of beds occupied during the year. The cost of out-patients should be reckoned separately. It is interesting to note how widely the conditions of admission and support of patients differ in Great Britain and America. In twelve large hospitals in Great Britain each in-patient must provide for himself tea, butter and sugar. In three hospitals he must bring, in addition, a teacup and saucer, spoon, knife and fork, soap and towel. In fifteen hospitals he must provide a change of personal linen and pay for his own washing. In eighteen hospitals alone are in-patients freed from these extra charges, which must be a serious burden upon their friends and a prolific source of misunderstanding between nurses and patients. In such a wealth of information as is here given upon all topics connected with hospital and training school management, it is diilicult to discuss any toi)ic with any adequate fullness in this brief review. The book must be carefully examined by practical hospital workers to be fully appreciated.

Disease and Race. By Jaduoo. (London : Swan Soniienschcin tt Co., 1894.)

The object of this little book is stated to be " an endeavor to show some continuity in disease, to evolve a little order out of existing chaos." The attempt is commendable, hut the success of the effort is not great. The order evolved out of existing chaos is largely theoretical and hypothetical, and tends to confuse rather than to nnike plain. Leprosy is first spoken of, and an effort is made to show that the leprosy of the Bible differs in many rcsjiects from

leprosy as it appears to-day. Instead of reaching the obvious conclusion that the term translated by the word leprosy possibly included a variety of diseases like psoriasis, scabies and otiier forms of contagious disease, the author considers that true leprosy as it now appears is a hybrid disease produced by the combination of Jewish or white leprosy and some other disease wliich has developed in the countries bordering on the Mediterranean in modern times. This he suggests probably originally came from America, and meeting the existing form of leprosy, the two diseases produced a compound or hybrid, taking most of the effects and symptoms of each of them and continuing their course through succeeding generations as one disease, neither being to a sufficient degree either liereditary or contagious to extinguish the other by successive natural inoculations. The result has been to modify the character and especially the contagiousness of leprosy, until as now it appears considerable doubt is expressed by some authors as to its being contagious at all. He further reasons that leprosy and gonorrhoea have produced syphilis, whicli in turn has been modified by successive transmissions into scrofula, and finally into tuberculosis. Whooping-cough iias been modified into measles, and Aleppo-button into plague, and the two latter have combined and produced small-pox. Malarial fever has been modified into miliary fever, and this has been transformed into scarlet fever, and finally into di]ihtheria — this is surely "a continuity in disease" which would be interesting to study if true. These conclusions are evidently based upon the fact which has long been known, that many forms of disease become modified by passing through individuals, until a severe type at the beginning of an epidemic may become a comparatively mild one at the latter point of it, and the added fact that one attack of an infectious disease often confers an immunity from subsequent attacks. Reasoning from these analogies, our author believes that diseases are so modified as to become essentially new diseases which finally find the race immune to their attacks. This, however, is pure hypothesis. As a matter of fact we have no reason to think the poison of smallpox any less severe except where the severity of the disease has been modified by vaccination. Plague and measles would probably be as severe and contagious as formerly were it not for improved sanitation and more healthful modes of living. Tuberculosis is probably more wide-spread and more fatal now than ever before. The following will serve as a good example of his reasoning :

" That the American continent was either the original home of leprosy or one of its modifications is extremely probable, by the fact of the comparative immunity of the pure-blooded aborigines from leprosy ; and this does not shut out the possibility that the disease arose and ran its course in America prior to the commencement of the disease in the Old World from a like cause." This is not unlike the old reason why syphilis was thought to have originated in America because guaiacum was found native here, and it was altogether probable that this disease and what w.is regarded its only infallible remedy must have been associated. The theory of hybrid diseases enunciated by the author has no countenance in modern bacteriology and cannot be accepted. The book, while interesting as a contribution to speculative medicine, is inconclusive and unsatisfactory.

"The Nurse's Dictionary of Medical Terms and Nursing Treatment, compiled for the use of nurses, and containing descriptions of the principal medical and nursing terras and abbreviations, instruments, drugs, diseases, accidents, treatments, physiological names, operations, foods, appliances, etc., etc., encountered in the ward or sick room. By Honnkr Morten. {PhiUidclpfiia : W. B. Saundert. London : The Scientific Press, Limited.)

Whatever may be said as to the wisdom of publishing compiI.<i. tions of this character, which do not attain the dignity of dictionaries or nurses' manuals and are somewh.it uns;itisfaolory from Ixith standpoints, there can be no question that the modicum of knowledge contained in them should be free from misleading errors. The

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number of typoprapliical errors in the volume before us seems extraordinarily large, as for example, accouclier for accoucheur, Bssafcctida for asafcetida, bulbus oceuli for bulhus oculi, cacoglactic instead of cacogalactic, concha oris instead of concha auris, phagosites instead of phagocytes, pierotoxine instead of picrotoxine, salens instead of soUus, bilirubrin for bilirubin, etc.

The combination of medical definitions and nursing directions is also far from a happy one. The following will serve as good examples of the method. "Abdomen : The belly ; the cavity betweenthe chest and the groins. In abdominal injuries a nurse has usually to keep her patient at rest and watch for signs of peritonitis. Laparotomy is the operation likely to be performed." "Antitoxines : Injections of serum to counteract a disease. Tetanus is sometimes treated by injections from rabbits rendered incapable of taking the disease."

The definitions alone seem hanlly more happy, as a few will readily show, e. g. "Anthracosis : Carbuncular disease (?) caused by inspiring particles of coal." "Argyll-Robertson pupil : Pupil of the eye which does not contract when subjected to light." " Bacteria : Rod-like uncTohes supposed to infect the blood with different diseases. They are unicellular and of fungous growth." Manj' important words are omitted, and many unimportant quack preparations are mentioned and defined, e. g. Warner's Safe Cure, Vinolia preparations, Beecham's Pills, and other equally unnecessary articles.

It would seem much better to divide "Medical Terms" from " Nursing Treatment," as the two portions of the book have little in common. A good dictionary of terms which nurses will meet with, correctly spelled and concisely, accurately defined, would be a great convenience to nurses. A similar little volume, giving plain, simple descriptions of diseased conditions and furnishing clear directions as to the course to be pursued in emergencies, would also serve an excellent purpose. The combination attempted in the present book cannot be commended. The book is clearly, neatly printed, and the volume is a convenient size to carry in the pocket.

Chorea and Choreiform Affections. By William Osler, M. D. (H. K. Lewis, London, 1894.)

In- this monograph of 120 pages of letterpress, Prof. Osier has presented to the medical profession a concise treatise upon the various forms of chorea and allied muscular spasms, which constitutes a distinct advance on former publications upon these subjects.

In the opening chapter a very interesting account is given of the earlier historic writings upon the subject, and a few pages further on, the principal more recent contributions to the literature, from England, the European continent, and from America, ftre outlined. In the next chapter the obscure etiology of the disorder is fully considered. Symptomatology occupies the succeeding two chapters, with a number of abstracts of graphic cases of mild and severe chorea. Chapter IV, "The Heart in Chorea Minor," is one of more than usual interest, and the great frequency of endocarditis in chorea is brought to the attention of the reader with the author's usual care and fidelity of detail. Attention is drawn to the fact that in the majority of cases of endocardial trouble in chorea minor, "the endocarditis is independent of, and not associated with acute arthritis, and that in a considerable proportion of cases, much larger than has hitherto been supposed, the complicating endocarditis lays the foundation of organic heart disease."

Chapter V treats of the anatomy, pathology, and treatment of the disorder. The author appears to be more inclined to consider chorea, in the strict sense of the word, to be of infectious rather than other nature, though truly, as he states, "we are evidently as yet only upon the threshold of the essential cause of either acute rheumatism or chorea. In both disorders there are facts highly

suggestive of an infectious nature, but more than this cannot be said at present."

Chapter VI leads to the consideration of choreiform affections. The various forms of habit spasm are very clearly defined, and it is pleasing to the reader to note how clearly Dr. Osier has drawn the distinction between these affections, so many of which are commonly confounded with the chorea of Sydenham. A considerable number of illustrative cases are introduced for the purpose of differentiating the various forms of spasm.

In the final chapter of the book, " Chronic Progressive Chorea " is considered from an historical, etiological, and clinical standpoint, but nothing especially new is developed. The last nine pages of the work are occupied by a careful analysis of seventy-three fatal cases of chorea minor, all but four showing heart lesions mainly in the form of endocarditis.

The monograph, from the introduction to the last page, is well written and very readable ; and will probably for a long time occupy a standard place in the literature of one of the most extraordinary maladies that affects the human race. H. J. B.

THE JOHNS HOPKINS HOSPITAL REPORTS,

THE JOHNS HOPKINS HOSPITAL.

Vol. v.- No. 43.

BALTIMORE, NOVEMBER, 1894.

+++

Contents

Papillo-Cystoma of the Ovary. By T. S. Cullen, M. B., - - 103

The Leucocytes in Croupous Pneumonia. By John S. Billings, Jr., M. D., 105

A Postscript to the Report on Appendicitis. By W. S. HalSTED, M. D., 113

Therapeutic Use of Extract of Bone Marrow. By John S.

Billings, Jb., M. D., - - - 115

Proceeilinga of Societies : Hospital Medical Society, 119

Case of Hereditary Chorea [Dr. Osler] ;— Oliver Wendell Holmes [Dr. Osler] ;— Ureterotomy [Dr. Kelly] ;— Sarcoma in the Floor of the Mouth. Excision followed by Hypertrophy of the left Submaxillary Gland [Dr. Bloodgood] ; — A Case of Typhoid-Septicaemia associated with Focal Abscesses in the Kidney, due to the Typhoid Bacillus [Dr. Flexner] ; — On the Presence of Iron in the Granules of the Eosinophile-Leucocytes [Dr. Barker]. Notes on New Books, 121

PAPILLO-CYSTOMA OF THE OVARY.

By T. S. Cullen, M. B.,

Although papilloma of the ovary is not particularly rare, this case is published on account of the involvement of both ovaries and because the places of origin are considered as being of interest. Moreover, as will be seen, the specimen was quite perfect.

Mrs. K., admitted to the service of Dr. Kelly, 2, 14, 1894. ^t. 41, married.

The patient comphiined of abdominal enlargement accompanied by loss of flesh and strength. She has been married 22 years and had one normal labor 20 years ago. Her only previous illness was typhoid fever, 10 years ago.

Present Illness. — In February, 1893, she began to feel languid, and was with difficulty able to continue her housework. In July she noticed a slight burning sensation in the right hypogastrium, not affected by exercise nor influenced by menstruation. Her body weight began to decrease. About September the abdomen commenced to enlarge and continued to increase in size. Tlie weakness and emaciation also were progressive. In November she vomited a greenish fluid. Defecation was accompanied by some pain in the pelvis. Since that time there has been little change.

Menstruation commenced in her eleventh year, was regular, moderate in amount and somewhat painful. In November, the menses suddenhj ceased and have not recurred.

Physical Examination. — The patient is fairly well nourished. Her mucous membranes are somewhat anaMuic. Heart and

Assistant in Gynecology.

lungs apparently normal. Liver dulness not increased. The abdomen is enormously and symmetrically distended. The greatest prominence is below the umbilicus. The linese albicantes in the lower abdominal zone are very prominent. The superficial veins are distended.

Palpation. — Some superficial a?dema above the symphysis pubis. No masses to be felt.

Percussion. — No tympanitic note can be elicited below the umbilicus. A distinct wave of fluctuation is felt. Above the umbilicus the tympany extends 16 cm. to the right and 12 cm. to the left of the median line.

Abdominal Measurements. —

Umbilicus to ensiform cartilage 21 cm.

" " pubes 27 "

" " right anterior superior spine 27 "

" " left anterior superior spine 27 "

Greatest circumference 145 cm., at the umbilicus.

Vaginal Examifmtion. — The outlet is greatly relaxed. The cervix is in the axis of the vagina ; uterus retroflexed. apparently fixed in the pelvis. No tumor felt

Per rectum. — In Douglas's pouch a mass of indefinite size can be detected, conveying the impression of small papillomatous masses.

2, 17, 1894. Operation by Dr. Kelly, double cystectomy. On opening the abdomen 17 litres of fluid were found free in

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the cavity. Ou both sides large cj'sts were seen, occupying Douglas's cul-de-sac ; by these the uterus was pushed forward. The left side was elevated, tied ofE and removed without difficulty. The right side was enucleated after being liberated from dense adhesions to the broad ligament and to the postei-ior surface of the uterus. Adhesions between the bladder and broad ligament were cut, and about eight small papillary nodules were excised from the pelvic floor. It was impossible, however, to remove all of them on account of their intimate relation to the bowel. The peritoneum was thoroughly sponged out and the wound closed. Silk sutures were used throughout. During the third week the temperature rose to 101.8° and fluctuated between that and 99.5° for throe days, otherwise the patient had an uninterrupted recovery, and was discharged on March 20, feeling well.

Pathological Jieport. — RigJit side, the ovary is replaced by a tumor 8.5x8x7 cm. This is irregular in contour, being made up of several cysts, varying in size. These cysts ai'C bluishwhite and translucent. The most dependent part of the tumor is yellowish in color. Springing from the uterine side of the tumor is a pinkish cauliflower-like mass which has a somewhat narrowed base. The interior of the tumor is occupied by Ave cysts; these are smooth-walled, but have, developed upon their inner surfaces, small papillary-like masses. The fluid in the large cyst is somewhat tenacious, in the smaller ones limpid. The tube is 4 cm. long, 5 mm. in, diameter. Its flmbrlated end is free. Parovarium is normal.

Microscopically. — The cyst walls are composed of connective tissue moderately rich In cells. Several corpora fibrosa are scattered throughout the wall. The outer surface is lined by flat epithelium. The papillary masses springing from the outer surface are composed of finger-like projections of connective tissue which become branched toward their termination. The connective tissue near its attachment to the cyst wall is moderately rich in cells, but as it passes outward the cells diminish in number and the stroma presents a hyaline appearance. The surface epithelium as it approaches the papillary masses becomes cuboidal, and where covering the masses is cylindrical. The inner surface of the cyst wall, is lined by cylindrical epithelium. The papillary masses springing from the interior. Fig. 3, present the same appearance as those on the outer surface, but appear to have no connection with them.

Left Side. — The ovary is converted into a similar tumor of

the same size ; here, however, the papillary masses tended to spring from the depressions between the cysts. Both tubes normal.

Source of Origin. — The outer ones undoubtedly spring from the germinal epithelium. It is the opinion of Professor Welch that those on the inner surface of the cysts originated in the cells of the Graafian follicles ; the cysts forming first, and the papillary masses developing secondarily. This mode of origin is, we consider, indicated by the small number of cysts present. The small masses from the tissue surrounding the rectum presented a typical papillary appearance.

Professor Abel made a chemical examination of the fluid from the abdominal cavity. The fluid was yellowish in color and presented a greenish tinge, was alkaline in reaction and had a specific gravity of 1020. It contained serum albumen, serum globulin, a trace of sugar and fibi'in.

Although the prognosis in this case was considered unfavorable owing to the incomplete operation, the patient has, during the six months following the operation, gained 49 pounds.

The sudden cessation of menstruation is of especial interest as associated with the diseased condition of the ovaries.

Description of Plate.

Fig. 1.— Natural size of tumor from right side, hardened in Miiller's fluid and then cut open. Springing from its outer surface are papillary masses. Internally it is composed of one large and several smaller cysts. Projecting from the inner surface of these are papillary masses. The large cyst, c, contains a tens^cious fluid which was coagulated by the Miiller's fluid, a is a cross section of the normal Fallopian tube.

Fig. 2 is the other half of Fig. 1. The coagulated fluid has been washed out of the large cyst cavity, enabling one to see the papillary masses more distinctly.

Fig. 3 is a section of a small nodule taken from the inner surface of the cyst in Fig. 1 at the point represented by b. (Winckel Ocul. I, Obj. 3.) d is the cyst wall, which is composed of wavy fibrous tissue poor in blood supply. The inner surface of the cyst is covered by one layer of cylindrical epithelium. The papillary mass presents a tree-like appearance. It also is composed of connective tissue, which becomes less dense tlie farther it is away from the cyst wall. All the folds and convolutions of this papillary mass are covered by one layer of cylindrical epithelium. In some places the cells have been cut slantingly and then look somewhat like squamous epithelium. The orange-colored areas are blood-vessels.

THE LEUCOCYTES IN CROUPOUS PNEUMONIA

By John S. Billings, Jr., Assistant Resident Physician, Johns HopTcins Hospital.

The increase in the number of leucocytes in the blood in croupous pneumonia may be said to have been first noticed by Piorry'in 1839. He remarked that the so-called "crusta phlogistica," seen above the clotted blood withdrawn by venesection from patients suffering from any of the acute inflammatory diseases, was most marked in pneumonia. It was thickest at about the seventh or eighth day, just before the crisis, and he thought it to be due to an hsmitis or an actual inflammation of the blood itself.

Virchow^ in 1871 spoke of a leucocytosis in pneumonia and held that there was an actual new formation of leucocytes, i. e. an absolute increase in the total number present in the circulation, but only in those cases in which there was swelling of the bronchial glands.

Since then there have been many investigations on the subject, especially in the last four years. Nasse,' Koblanck, Sorensen and Pee all noted the presence of a leucocytosis during the course of croupous pneumonia, but they did not speak of its relation to the temperature, nor to prognosis.

Halla' in 1883 was the first to report a series of cases, fourteen in number. In twelve of these there was a leucocytosis, while in the I'emaining two the leucocytes were not increased. Both the latter cases ended fatally. He was the first to call attention to the fact that the absence of leucocytosis is of biid omen. He found no correspondence between the temperature and leucocyte curves in those cases ending in recovery.

Hayem and Gilbert* in 1884 remarked upon the typhoid character of those cases of pneumonia in which there is no leucocytosis.

Tumas" in 1887 stated that there was a rough daily correspondence between the temperature and the leucocytes, and that the number of the latter was greatest at the severest stages of the disease. He also noted that the leucocytes did not reach normal at the same time as the temperature, but remained elevated for three or four days after the crisis.

Boekniaun' and Von Jaksch' claim that there is a constant relation between the number of leucocytes and the temperature in various acute infectious diseases, and particularly in pneumonia.

Kikodse' states that leucocytosis is absent only in fatal cases. He believes that the leucocytosis begins before the involvement of the lung takes place, that it runs parallel with the temperature, and falls to a jxiint below normal with the crisis in temperature.

Eoemer" believes the leucocytosis in pneumonia to be caused by the products of destruction (bacteria, cells, etc.) brought about by the alkali-proteins, and not directly by the alkaliproteins themselves.

Von Jaksch," recognizing the bad prognosis in cases which showed no leucocytosis, and believing that the fatal termination was due directly to its absence, I'ecommended the use of drugs which would produce an increase in the number of leucocytes in the blood. (Antipyrin, pilocarpin, etc.) Such treatment was ineffectual, as will be demonstrated later.

Maragliano" does not think that the number of leucocytes is of any prognostic value.

Rieder" rejjorts his observations in twenty-six cases. He finds that the fall of the leucocytes generally precedes the fall of temperature, but that the number of the leucocytes, while beginning to fall first, may often remain elevated for several days after the temperature has touched normal. This is particularly marked in cases of delayed resolution. In cases ending by lysis the leucocytes fall correspondingly slowly. A pseudo-crisis may be recognized by the fact that while the temperature may fall to normal, the leucocytes remain steadily elevated. He finds no correspondence of the leucocyte and temperature curves. The leucocytosis was present in one case six hours' after the chill. In fatal cases there was no leucocytosis, but the blood showed the characteristic change noted in so-called pure leucocytoses, i. e., a marked relative increase in the number of so-called polynuclear elements. He does not think there is any relation between the amount of leucocytosis and extent of lung involved.

V. Limbeck" holds that only those infectious diseases with exudation into the tissues show an increase in number of the leucocytes. The amount of leucocytosis depends upon the quality and quantity of the exudate, i. e., the more cells and the larger the exudate, the greater the leucocytosis. He states that in pneumonia the leucocytosis disappears with the fever. Should there be a new extension of the disease and a rise of fever, the leucocytosis reappears a few hours before the rise in temperature takes place. A pseudo-crisis may be recognized by a steady leucocytosis. A fatal ending is foreshadowed by a steady rise in the number of the leucocytes.

Tchistovitch inoculated rabbits with cultures of pneumococcus and found a leucocytosis only in those cases ending in recovery. The use of sti'onger cultures which killed the animal did not cause any leucocytosis, but brought about an actual reduction in the number of the leucocytes, t. e., a so-called Icukolysis. This was confirmed by Kieder (1. c).

Laehr'^ reports observations of the leucocytes iu sixteen cases of pneumonia. He found the leucocytosis in one ease to be present eight hours after the chill. The leucocytes rise one to two days before the crisis, to sink again before the crisis takes place. The temperature reaches normal Ix'fore the leucocytes. lie finds no exact correspondence between the number of leucocytes, the fever and the amount of lung involved, but thinks they do correspond roughly. He believes the leucocytosis to be due to chemotaxis, the attracting substances being the alkali-proteins, etc.. produceii by the pueumococcus. Persistence of the leucocytosis signifies delayed resolution of the pneumonic consolidation, and its reqijH'arance indicates a recurrence of the disease.

Schulz"' states that the leucocytosis observetl iu pneumonia, as well as all other inflammatory leucocytoses, is not due to any absolute increase in the numltor of leucocytes iu the circulation, but only an altereti division. He believes that in health the large abdominal vessels contain manv more leuco

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cyt€s ("Wandstaadig ") than the peripheral vessels. In disease the presence of abnormal chemotactic substances in the blood, and the increased rapidity and force of the respiration and circulation, are enough to drive these e.xtra leucocytes out i:ito the circulation and to those points where they may be needed.

Rovighi" states that in pneumonia the leucocytes reach their highest point during the period of fall of temperature. He bases this statement on the results of experiments going to show that when the body is heated the number of leucocytes in the peripheral circulation diminishes, while cooling the body increases their number. These are purely local phenomena, not due in any way to changes on the part of the blood-making organs.

Cabot" reports observations in seventy -two cases of pneumonia. Seven of these ended fatally, and six out of the seven showed no leucocytosis. In one case ending in recover}^ which showed no leucocytosis at first, there was a steady rise in the number of the leucocytes towards the end of the disease. He does not think that there is any relation between the amount of leucocytosis, the degree of severity of the case, and amount of lung involved.

Ewing^" reports a number of cases, and draws the following conclusions. 1. The greater the amount of lung involved, the greater the leucocytosis. 2. The amount of leucocytosis corresponds to the "systemic reaction," the latter being judged by the temperature, pulse and general condition of the patient : i. e., in fatal cases there is no leucocytosis, and 7nce versa. 3. A well marked leucocytosis indicates a severe infection, a low leucocytosis is unfavorable, and the absence of any leucocytosis makes the prognosis very grave.

Tchistovitch"' reports the results of some further inoculation experiments upon animals. As is well known, the inoculation of animals with certain substances (tuberculin, sterile culture of staph, py. aur., and pilocarpin) produces first a temporary leukolysis (so-called), which is followed by a marked leucocytosis. He found that those substances which produce a leucocytosis in healthy rabbits do not do so when injected into rabbits previously inoculated with virulent cultures of pneumococcus. The progressive diminution of the leucocytes caused by the latter substance steadily continues, or at most there is only a slight transient leucocytosis, which is followed by a fresh fall. He holds this to show that those cases of pneumonia which succumb to the great virulence of the specific pneumococcus, should show no leucocytosis, and that no stimulant of leucocytosis should be able to produce any leucocytosis in such cases. So that the presence of a leucocytosis in fatal cases of pneumonia should make us doubt that the virulence of the specific pneumococcus was the cause of death, and we should seek some other cause of death in such cases, such as extensive involvement of the lungs or localization of the disease in the heart or in the brain.

When he injected the pneumococcus culture into the brain of tlie animal there was produced a meningo-encephalitis with a marked rise in the number of leucocytes in the blood. The amount of culture used was just so much as, injected elsewhere in the body, would bring about a severe infection with leukolysis, but without fatal termination. In conclusion, he holds that the presence or absence of leucocytosis only shows

the virulence of the poison and is not a criterion of absolute prognosis.

He saw four fatal cases of pneumonia. In one there was no leucocytosis. Of the other three, all of which showed a leucocytosis, one had endocarditis and meningitis, another meningitis, while the third case showed extensive consolidation of both lungs.

Biegauski'" reports a series of cases, paying especial attention to the relative numerical proportions of the various forms of leucocytes. In cases showing a marked leucocytosis, 80 to 90 per cent, of the leucocytes are polynuclears, while the eosinophiles and blood-plates are practically absent. Just after the crisis in temperature the polynuclears sink to below 60 per cent., wliile the eosinophiles and blood-plates reappear in increased numbers, about three days being taken for the blood to return to its normal condition. In fatal cases the polynuclears are reduced to 50 per cent, or below. Such a condition of the blood together with an absence of leucocytosis makes the prognosis unfavorable.

He holds that the leucocytosis in pneumonia is due to a lessened destruction of the polynuclear forms. This is brought about by the toxines of bacterial origin which are circulating in the blood. The mononuclear elements are unaffected and continue to enter the circulation and to develop there into polynuclears. Here all progress ceases and there is neither any destruction of the polynuclears with formation of blood plates, nor further development of the polynuclears into eosinophiles. In the fatal cases the toxines are supposed to have a paralyzing effect upon the development of all the forms of leucocytes, and also to prevent the entrance of young forms into the circulation.

The twenty-two cases here reported were not picked ones, excepting that eight or ten were thrown out, either because too few counts were made or because the crisis in temperature occurred witliin twenty-four hours after entry into hospital. The methods and precautions used in counting the blood, and in examining and preparing tkied and stained specimens, were exactly the same as those employed in the investigations of the leucocytes in malarial fever reported by the writer in the October number of this journal for 1894.

In each case charts were made of the leucocyte and temperature curves, so that comparison of the two could readily be made. Three of these charts are reproduced in this article. The leucocytes were counted on an average of twice a day during the febrile period.

Cases.

1. W. R., a;t. 26. Illness lasted 12 days. Right middle, right lower and left lower lobes involved. Temperature ranged high until sixth day, when it .fell by lysis, taking 6 days to reach normal. Leucocytes 39,500 six hours after chill. \o daily correspondence with temperature curve ; they reached their highest point (50,000) two hours after temperature began to fall. Thenceforth they fell steadil}', reaching normal one day after temperature.

2. S. F., fet. 51. Illness lasted 8 days. Right middle and lower lobes involved. Temperature ranged at 102° for 6 days ; fell by lysis, reaching normal in 50 hours. Leucocytes 42,000

Case 4. Pneumonia and Rheumatic Fever. Showing fall hy Lysis.

8 hours after chill. They fell steadily until temperature began to fall, when they rose sharply to 38,000, reaching normal 3 days after temperature.

3. H. H., ffit. 23. Illness lasted 17 days. Right middle and lower lobes involved, with delayed resolution. Temperature fell on seventh day of disease, to rise again sharply to 102°. Fell again by lysis, reaching normal in .5 days. Leucocytes ranged between 20,000 and 28,000 until the day the temperature touched normal, when they began to fall, reaching normal eleven days after temperature.

4. E. E., a?t. 42. Illness lasted 9 days. Right middle and lower lobes involved. For temperature and leucocytes see chart. Leucocytes reached highest point (27,000) during period of fall of temperature. They reached normal at the same time as the temperature. Two days afterwards P. was taken with acute rheumatic fever, with a simultaneous rise of temperature and leucocytes. P. still had rheumatism when discharged at his own request.

5. J. 8., set. 13. Illness lasted (i days. Right middle and lower lobes involved. For temperature and leucocytes see chart. Leucocytes rose during fall of temperature, but had reached their maximum before that time. They reached normal 36 hours after temperature, the crisis in which took 34 hours.

6. E. W., !Pt. 7. Illness lasted 9 days. Left lower lobe involved. Temperature ranged high until 8th day, when there was a pseudo-crisis, the temperature rising sharply afterwards. Crisis took place the following morning, lasting 2 hours. Leucocytes ranged at 34,000 until the true crisis took place, when they began to fall, but did not reach normal until two days after temperature.

7. G. S., set. 40. Alcoholic history. Illness lasted 7 days. Left upper lobe. Temperature ranged at 105 until 5th day, when it began to fall, reaching normal in 36 hours. leucocytes ranged very low during whole course of disease, reaching their maximum (13,000) during the period of fall of temperature. This, together with the history and situation of disease, made the prognosis a grave one, but patient made an uuiuterrupted recovery. ■

8. E. F., »t. 20. Illuess lasted 8 days. Right middle and lower lobes were involved, with delayed resolution. Temperature ranged high until the 7th day. when it fell by crisis, reaching nornuil in 10 hours. Leucocytes ranged at about 25,000 until crisis iu temperature, when there was a slight fall to 16,000, followed by a gradual rise to 27,000. the leucocytes not reaching normal until 7 days after temperature.

9. C. J., a?t, 30, Patient was admitted for tertian ui.alarial fever. Lungs were clear on admission, and the pneumonia

Case h. Pseumonia. Showing fall by Crisis.

began .36 hours later. For temperature and leucocytes see chart. Quinine was given on the evening of the chill, and the malarial organisms rajiidly disappeared, and with their disappearance the number of leucocytes rapidly increased. There was successive involvement of the right lower, right middle and left lower lobes, each fresh extension of the disease being followed by a sharp rise in the number of the leucocytes. Leucocytes reached highest point (68,000) just before the fall in temperature began, and thenceforth decreased in number, reaching normal 6 days after temperature.

10. E. M., ffit. 4.5. Illness lasted 10 days. Left upper lobe involved. Temperature ranged at 103° until 9th day, when it fell by crisis, reaching normal in IG hours. Leucocytes readied maximum (36,000) two days before crisis. They fell with temperature, but did not reach iionnal until two days after crisis.

11. C, aet. 26. Illness lasted 13 days. Kight upper, middle and lower lobes involved. Temperature ranged at 104° until

11th day, when it fell by crisis, i-eachiug normal in 48 hours. Leucocytes low on admission; reached ma.ximum (29,000) during period of fall of temperature. Did not reach normal until 7 days after temperature.

12. L. K., ffit. 24. Illness lasted 8 days. Right lower lobe involved. Temperature ranged high until 8th day, when it fell to normal in 24 hours. Leucocytes ranged at 25,000 until crisis in temperature occurred, when they fell to 16,000, but rose again to 29,000 (maximum). They did not reach normal until 8 days after temperature. Delayed resolution.

13. J. IL, ajt. 41. Illness lasted 10 days. Right upper lobe involved. Temperature ranged between 102° and 104° until day of death, when it fell, being 100° 2 hours before death. Leucocytes 22,000 on admission, rose to 38,000 that p. m., falling steadily afterwards. 10,000 just before death. No autopsy.

14. J. W., net. 73. Illness lasted 8 days. Right upper, middle and lower lobes involved. Temperature ranged at

Case 9. Pneumonia and Malaria. Siiouinc. fall by Ckisis.

101° until .30 hours before deiitli, wlieu it rose to 10-1°. Leucocytes ranged at 25,000 from admission until death. Autopsy. In addition to pneumonic consolidation above noted, P. had an acute fibrino-purulent meningitis due to the dip. pneumoniae.

15. G. W., aet. 35. Illness lasted 10 days. Right upper, middle and lower and left lower lobes involved. Temperature ranged from 101.5° to 104°, being 104.3° at death. Leucocytes 8,000 on admission, rose steadily until time of death 8 days later, when they were 30,000. Autopsy showed the pneumonic consolidation above noted. No meningitis nor endocarditis.

16. K. D., a;t. 47. Illness lasted 4 days. Right upper and middle lobes involved. Temperature ranged at 102.5° until death, with a pseudo-crisis to 99° 12 hours before death. Leucocytes 18,000 on admission, where they ranged until death. 15,000 just before death. No autopsy.

17. C. L., a?t. 3G. Illness lasted 21 days (,?V Lower lobes of both lungs involved. Temperature ranged steadily at 102° until 12 hours before death, when there was a pseudo-crisis to 99°, with a sharp rise to 103° just before death. Leucocytes 13,000 on admission, fell gradually to normal iu two davs. They began to rise 36 hours before death, reaching 32.000 just before the end. No autopsy.

18. J. C, a;t. 63. Illness Listed 11 days. Right middle and lower lobes involved. Temperature ranged at 103.5° until 2 days before death, when it rose to 106.2°, falling to 104° just before death. leucocytes S.OOO ou admission. Remained normal until day before death, when they rose to 30.000. falling to 14.000 before death. No autopsy.

19. F. tS.. :et. 50. History of alcoholism. Illness lasted 24 days (?). Right upper and middle lobes iavolve<L Temix^rature ranged at 104° during the four days preceding death.

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The afternoon of the fourth day the P., being left alone for a moment, climbed through the top of a window and fell to the ground outside, breaking vertebral column and both bones of right leg. Unsatisfactory coroner's inquest showed nothing beyond the fractures and the pneumonic consolidation above noted. Leucocytes 15,000 on admission; for the first 3 days fell gradually to 11,000, but after the accident above referred to, rose to 18,000. P. lived 4 hours after the accident occurred.

•ZO. H. L., tet. 41. Illness lasted 5 days. Right lower base involved. Temperature on admission 102.5°. For next three days it ranged at 104°, being 103.8° just before death. Leucocytes 10,000 on admission, after which time they ranged steadily below normal ; from 6,000 to 1,500. They were 4,000 just before death. Ko autopsy.

21. A. N., set. 47. Illness lasted 12 days. Lower lobes of both lungs involved. Temperature ranged from 103.5°-105°, until shortly before death, when it rose to 107°. Leucocytes 15,000 on admission ; 3 days later they rose to 28,000. Eanged at 22,000 until just before death, when they touched 30,000. So autopsy.

22. A. P., set. 22. Illness lasted 3 days. Left lower lobe

leucocytes were 39,500 and 43,000 6 and 8 hours after the chill, respectively.

Of the eight eases ending by crisis, in all but one there was a marked leucocytosis during the febrile period of the disease. In the remaining case the leucocytes, while ranging at normal during the greater period of the disease, touched 13,000 on one occasion. [Case 7.] Examination of the combined charts showed no daily correspondence of the two curves before crisis occurred. The leucocytes began to fall before the temperature in three cases, with it in two, and after it in three. The fall of leucocytes was only partial in six cases, however, and they did not reach normal until from two to eight days after the temperature. In cases 6 and 7 the leucocytes and temperature reached normal at the same time. In cases 7, 9, 11 and 12 the leucocytes reached their maximum daring the period of fall of temperature. In cases 5 and 8 there was a rise of leucocytes during that period, but the maximum had been previously attained. Most of these points are well shown in a combined chart of the eight cases, showing the average temperature and number of leucocytes, twelve, twenty-four and thirty-six hours before and after the crisis in temperature.

involved. Temperatui'e ranged steadily at 103° until death. Leucocytes 50,000 on admission ; fell steadily, being 20,000 when death occurred. Autopsy showed beside a double lobar

Taking up hrst the four cases ending by lysis, we see that in all there was a marked leucocytosis at some period of the disease. Examination of the combined leucocyte and temperature charts showed that before the temperature began to

fall there was no daily correspondence between the two curves. In all four cases the two curves began to fall together, the leucocytes not reaching normal until one, four and 'fourteen days after the temperature in cases 1, 2 and 3 respectively. In case 3 there was delayed resolution of the consolidation, it not having entirely cleared up on discharge.

In cases 1 and 3 the leucocytes reached their niaxiDuun during the period of fall of temperature. There was a iff&rp rise during that period in case 3, but the maximum had been reached before the temperature began to fall.

In case 1, where there was involvement of both lungs, the leucocytes reached 50,000. In the other three cases the lower portion of the right lung was involved and the range of the leucocyte curves was moderate, being above 30,000 in only one instance.

In cases 1,2 and 4 the fall in temperature preceded the fall of leucocytes.

Case 4 is interesting on account of its complication with rheumatism. The combined chart is given and it shows well the correspondence of the two curves. The occurrence of a moderate leucocytosis during the course of rheumatic fever has been mentioned by several observers. In cases 1 and 2 the

Blaclt = Uuciciitcs. Drnhcn = tfinpa-ature.

Chart showing Temperature and Leucocyte Curves op

Pneumonia. Crisis.

In case 9 the lower portions of both lobes were involved and the leucocytes touched the highest point reached in any of the cases, viz., 68,000. In case 11 however, where there was the same extent of involvement, the leucocytes only reached 29,000. In case 7 only the left upper lobe was involved and the leucocyte range was practically normal, only once being above 10,000. The prognosis in this case was thought to be grave at first on account of the absence of leucocytosis, the position of the consolidation, the alcoholic history and patient's age. The patient made an uninterrupted recovery however, and the infection was evidently a very mild one. In the other live cases only a portion of one lung was involved and the leucocyte curve ranged moderately high.

In only one of the eight cases was it possible to count the blood before and after the chill. This was case 9, in which the pneumonia came on while patient was being treated for malarial fever of the double tertian type. In the article on the leucocytes in malarial fever, previously referred to, the

November, 1894.]

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fact is brought out that in malarial fever the leucocytes range constantly below normal during the course of the disease. This is due in some way to the presence of the malarial organism in the blood. It is not settled as to whether it is a leukocytolysis (an actual destruction of leucocytes) or a leukopenia (a diminished production). Now in case 9 there was no leucocytosis either before or after the chill, until the exhibition of quinine caused the disappearance of the malarial organisms from the blood, when the leucocytes promptly rose. It is interesting to note how, as each new portion of the lung was involved, there was a corresponding rise in the number of the leucocytes. [See chart.]

Of the ten fatal cases only one (No. 20) showed a complete absence of leucocytosis during the entire course of the disease. In cases IG and 19 the leucocytes, while being always above normal, ranged relatively low, never being above 19,000. In case 14 the leucocytes behaved as one would expect them to in an uncomplicated case ending in recovery. In cases 1.5, 17 and 21 the leucocytes were practically normal on admission, biit gradually rose dui'ing the ensuing three or four days, touching just before death .30,000, 32,000 and 30,000 respectively. In cases 13 and 22 the leucocytes were high on admission, but fell steadily from that time on until death. In case 18 they were normal for the iirst two days, but rose sharply to 20,000 24 hours before death, falling slightly just before the end.

Thus we see that in fatal cases the behavior of the leiicocytes varies widely. In six cases there was absence of leucocytosis at some period of the disease, but the continuous absence is the exception, not the rule. In none of the cases was there any daily correspondence between the temperature and leucocyte curves. In the four cases in which the leucocytes rose at the end however, there was a corresponding rise in temperature. As regards the relation of the amount of leucocytosis to the extent of lung involvement, no definite conclusions can be drawn. In case 15, where the entire right lung and a portion of the left were involved, the maximum leucocytosis was only 30,000 just before death. None of the cases were seen until at least twenty-four hours after the chill, so that no data are furnished as to how early the leucocytosis appears.

Autopsies were obtainable in only three out of the ten cases. This does not include the coroner's inquest on case 19. The results of these autopsies bear out Tchistovitch's statements however. In case 14, where the leucocytes ranged above 20,000, an acute fibrino-purulent meningitis was found to be present. In case 15, where the leucocytes ranged from 17,000 to 30,000 for 5 days, extensive involvement of both lungs was found. In case 22, where the leucocytes ranged from 50,000 to 20,000, there was found at autopsy double lobar pneumonia, acute nephritis, fatty degeneration of the heart muscle, and haemorrhage into the pericardial sac, with the presence of the diplococcus pneumoniae in the latter situation. In case 19, where the leucocytes ranged at 18,000, the fracture of the spine was probably the immediate cause of death. In case 21 there was involvement of both lungs, with a leucocyte range above 20,000. All the remaining cases, with the exception of No. 13, showed a low range of leucocytes, and it is only fair

to consider it possible that in case 13 also, an autopsy might have revealed some complication or condition accounting for the relatively high leucocytosis.

There are a number of theories as to the cause of leucocytosis. Virchow held that it was due to proliferation within the lymph glands, that it only occurred in those cases of disease associated with glandular enlargement ; also that acute glandular enlargement was followed by leucocytosis. This is negatived by the absence of leucocytosis in many diseases accompanied by glandular enlargement (tuberculosis, acute Hodgkin's disease, etc.), and by the presence of marked leucocytosis in diseases associated with very slight glandular enlargement. [Pneumonia.] Every leucocytosis is probably associated with some glandular enlargement however. Such a leucocytosis as Virchow supposes would be a lymphocytosis, which is not the case.

Schulz's theory has been already mentioned. Its falsity would seem to be proved by the work of Goldscheider and Jacob (to be referred to later), who found that in cases showing a leucocytosis in the peripheral circulation, there was no corresponding diminution in the leucocytes in the central blood-vessels.

Romer (1. c.) thinks the increase due to direct multiplication (by amitosis) of the leucocytes, the exciting cause of such multiplication being the destruction-products of the alkaliproteins, as has been mentioned. He thinks chemotaxis to play a large part. No such changes as he infers are to be made out in the blood.

Von Limbeck (1. c.) holds leucocytosis to be due to the action (" Fernwirkung ") of the bacterial products themselves upon the leucocytes. He does not speculate as to the source from which the increase is drawn.

Bieganski's theory has been mentioned. Too little is known about the so-called blood-plates and eosinophiles to justify us in drawing conclusions from any variations in their number. Most authorities deny that the blood-plates are end-products of the polyuuclear leucocytes.

Lowit" holds that every leucocytosis is preceded by a diminution in the number of leucocytes. This is due, he thinks. to an actual destruction of the leucocytes, and he calls it leukolysis. This leukolysis is in turn followed by a pouring forth of young elements from the ha?matopoietic organs. This reparation far exceeds the destruction, in this way j^ii|ing about a leucocytosis. He demonstrates by injection experiments that the artificially-produced leucocytosis is preceded by a leukolysis. His ideas as to the source from which the increase is drawn would seem to l>e negatived by the absence of evidence of new formation. Were new formation to occur, the blood would show a large number of young elements. This it does not do.

The latest work on the subject is that of Goldscheider and Jacob". They make use of the t«?rms hypo- and hyj>erleucocytosis for leukolysis and leucocytosis respectively. Their conclusious are as follows : Ilypoleucocytosis is due to the leucocytes being driven into and detained within the capillaries of certain orgiius of the body. Actual destruction plays a minor role. Hyperleueocytosis is due to an increiised quantity of leucocvtes being carried to the blood by the lymph stream.

112

JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 43

There is no new formation of leucocytes, its absence being offset by the supposition that in the bone-marrow and spleen there are a large number of adult leucocytes held in reserve, as it were, which are carried off by the lymph stream into the general circulation when occasion arises. The occurrence of new formation is negatived by the absence of young forms in dried specimens.

All these phenomena are primarily due to the bacterial products or chemical substances in the blood. In most acute infectious diseases these substances are introduced into the circulation slowly and cause no diminution in number of the leucocytes, the latter rising immediately. This statement is borne out by experiment. This would mean that in pneumonia the leucocytosis would be found to be present at the time of the chill.

The authors are led to believe that the sources of the leucocytosis are the blood-making organs. But there is no evidence of new formation ; hence their theory of a reserve force of adult leucocytes within those organs. This theory seems rather to be constructed to meet the necessity of the case than to be founded on sufficient evidence.

Sherrington^ in a recent article reports observations of his own on inflammatory leucocytosis. He discusses most of the prevailing ideas, but formulates no new theory.

It is beyond the province of this article to enter into any further discussion of these theories. All we can sayis that the leucocytosis in pneumonia is probably due in some way to the products of the diplococcus pneumoniie. While the bacteria do not enter the blood as a rule, their products do, and in this way can influence the various organs of the body. There is probably no new formation of leucocytes, or at any rate it plays a minor role in the process, and some other source for the increase in number of the leucocytes must be sought for.

The behavior of the leucocytes depends upon the virulence of the bacterial products. In fatal cases where the virulence is great, a rise in the number of leucocytes is rendered impossible. It is doubtful whether there is any actual diminution of their number, there being no evidence that actual 'destruction of leucocytes takes place. The virulence may be so modified as to permit of a gradual increase in number of the leucocytes, yet still be potent to cause death. Cases may begin favorably and the leucocytes may range high at first ; the virulence of the bacterial products may then increase, causing a gradual reduction of the leucocytes, and death. The sharp rises sometimes observed just before death may be associated in some way with the pre-agonal leucocytoses. We must not forget that the disease may be present in so mild a form that the leucocytes are unaffected and remain normal throughout. This is shown in case 7 of our series. Most of the above points are shown in the following table:

1. V'ery mild infection : No effect on leucocytes. Normal range.

2. Moderate infection: Moderate leucocytosis.

3. Severe infection (as to e.\tent of lung involvement): Marked leucocytosis.

4. Severe infection (as to virulence of bacterial product): .Moderate leucocytosis.

.5. Very severe infection : No leucocytosis.

It has not been proved, as will be shown later, that the blood condition in the fatal cases differs in any way from the normal as regards the relative numerical proportions of the various forms of leucocytes.

If this be true, it is easy to see that the examination of the blood in pneumonia is not of absolute prognostic value. The blood only furnishes an indication of the virulence of the bacterial products; the extent of lung involvement, the general condition of the patient, and the temperature must also be taken into account in every case. For instance, should we be guided by the blood condition alone, our prognosis in cases coming under the heads of 1 and 5 in the above table would be either favorable or unfavorable according to the view we took. The error would of course be fatal.

The absence of leucocytosis in the fatal cases is evidently not the cause of death. Hence the failure of Von Jaksch's treatment by injecting such substances as would produce a leucocytosis in the healthy individual.

Regarding the question of the variations of the various forms of leucocytes, too much time was taken up by the actual counting to allow of much work in this direction. Twenty counts were made in the various cases showing a marked leucocytosis, with the following average result: Polynuclears, 91.2 per cent.; mononuclears, 9.6 jier cent.; eosinophiles, 0.2 per cent. Three counts were made in cases showing no leucocytosis, and the results were practically those which would have been obtained in counting the leucocytes in normal blood, thus agreeing with neither Rieder nor Bieganski.

Polynuclears.

(rt) 71.8 per cent.

(b) 73.5

(c) 76.1

Count (c) was in case 18. As has been mentioned, the leucocytes rose sharply just before death. A count was made two hours before death and the increase was found to be in tlie polynuclears solely. Polynuclears, 95.4 per cent. ; mononuclears, 4.3 per cent. ; eosinophiles, 0.3 per cent.

These counts would seem to make it doubtful that Bieganski's conclusions hold. The number of counts however, is too small to have any weight.

C0^fCLUSI0NS.

1. In cases of pneumonia pursuing a favorable course there is, as a rule, a marked increase in the number of the leucocytes during the febrile period of the disease. This leucocytosis is probably present at the time of the chill, and may be very marked within a few hours. There is no correspondence between the daily tonipcraturc and leucocyte curves during the febrile period.

2. In those cases in which the temperature curve falls by crisis, the leucocyte curve begins to fall within a few hours of the same time. The fall of the latter is only partial however, and rarely reaches normal as soon as the temperature curve, generally taking about 48 hours longer. In cases ending by lysis the two curves fall together, the temperature always reaching nornuil first. In cases of delayed resolution the leucocytes nuiy remain elevated for days.

Mononuclears.

Eosinophiles.

28.2 per cent.

26.1

0.4 per cent

23.4

0.5

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

113

3. In a majority of the cases the leucocyte curve rises during the period of fali of temperature, and may reach its maximum at that time. Such a rise is only transient, however, and is soon follpwed by a fresh fall.

4. In cases showing extensive involvement of both lungs, the leucocytes are apt to reach a higher point than in those cases whei'e the involvement is only moderate. The correspondence of lung involvement and amount of leucocytosis is a very rough one however.

5. The fatal cases may show either the presence or absence of leucocytosis. In those cases showing a leucocytosis, some other cause of death than the virulence of the bacterial poison must be sought for.

6. The prognosis in cases showing a complete and continuous absence of leucocytosis is unfavorable as a rule. A continuous absence of leucocytosis is the exception, most cases showing a leucocytosis at some period of the disease. The possibility of the absence of leucocytosis being due to extreme mildness of the disease must not be overlooked.

7. The leucocytosis in pneumonia is a so-called pure leucocytosis, i. e. an increase in the polynuclear elements solely. In cases showing no leucocytosis, the blood condition according to the observations here reported, is normal. Further investigations are necessary before the work of previous observers can be positively contradicted.

8. The presence or absence of leucocytosis only shows the

virulence of the bacterial poison, absolute prognosis.

Literature.

It is not a criterion of

Hamatopatliol., Leipzig, 1839.

Cellular Pathologie, 1871.

Untersuch. z. Phys. u. Path., 1889.

Prag. Zeitsch. f. Heilk., IV Bd., S. 198, 188.3.

Arch. Gen. d. Med., p. 257, 1884.

Deutsch. Arch. f. Klin. Med., Vol. 41, p. 323, 1837.

Arch. f. Klin. Med., Vol. 29, p. 481.

Festschr. f. Henoch., 1890.

Path. Anat. d. Blut. b. Croup. Lungcnentziindung. Inaug. Diss.,

Petersburgh, 1890. Berl. Klin. Woch., No. 36 & 51, 1891. Cb. f. Klin. Med., No. 5, 1892. Berl. Klin. Woch., p. 765, 1892. Beit, z Kennt. d. Leucocytose, Leipzig, 1892. Grundriss z. Klin. Path. d. Blutes, Jena, 1892. Ann. d. I'lnst. Pasteur, Vol. 5, pt. 7. Berl. Klin. Woch., No. 36 & 37, 1893. Arch. f. Klin. Med., 1893. 2 and 3. Arch. Ital. d. Clin. Med., No. 3, 1893. Bost. Med. and Surg. Jour., Vol. cxxx, No. 12. N. Y. Med. Jour., Dec. 16, 1S93.

Arch. d. Sc. Biol. Imp. Inst. St. Petersburgh, Vol. 2, No. 5, 1893. Deutsch. Arch. f. Klin. Med., Vol. 53, pts. 3 and 4, 1891. Studien z. Phys. und Path. d. Blut. u. d. Lymphe, Jena, 1892. Zeitsch. f. Klin. Med., Vol. 25, Pt. 5, 1894. Proc. Roy. Soc, Vol. 55, No. 332, pp. 161-206.

A. I'OSTSCRIPT TO THE REPORT OJSJ ^RRENDICITIS.*

By W. S. Halsted, M. D., Surgcon-in-Chief, etc.

Dr. Finney's remarks on the treatment of the wound in cases of appendicitis have been abbreviated so much as possibly to mislead those who are not familiar with our methods. When he speaks of "leaving the abdominal wound open" he means that the wound is drained with gauze, and not that no attempt is made to close it. The fact is that the wound is sewed up tight about the gauze, so tight that it is sometimes necessary to cut one stitch in order to remove the packing. Whenever pus is encountered either within the appendix or outside of it the wound is drained. Sometimes one or two narrow strips of gauze are sutlicient, sometimes very many broad strips are required. Ordinarily all of the gauze is brought out at one point and between stitches which, as I have said, embrace it snugly. The gauze is used not only for drainage, but quite as much to stimulate adhesions between the coils of intestine which surround it and thus effectually shut off the general peritoneal cavity from its infected portion. The gauze is gently packed about the stump of the appendix, and should reach into every recess of the pus cavity. AVhen tlie abscess is a large and ramifying one, or when there are several abscesses, we may bring the gauze packing out of the abdomen at more than one point in the wound.

These wounds are closed with mattress sutures ; but the sutures are not always buried as they are in all uninfected

• See Johns Hopkins Hospital Bulletin, June-July, ISOl.

abdomiinil wounds which are completely closed and in which the danger of stitch infection is not so great. The stitches, where they are not buried, are prevented from cutting into the skin by pieces of rubber tubing or of gauze. These wounds should be stitched with great care. All of the divided tissues (the peritoneum excepted) should be included in each stitch unless the stitches are buried. Inasmuch as the muscles retract unevenly the sewing is sometimes a difficult task. If the wound is sewed in this way, and if sufficient care is exercised to avoid the infection of the stitches as they are being introduced and tied, there is little if any danger that a hernia will ensue.*

Even the point at which the gauze traverses the abdominal wall is not a weak one. A connective tissue membniue, the wall of the obliterated sinus, extends from the stump of the appendix to this point in the wound and binds thciutestiues to

• At the meetingof the Johns Hopkins MedioAl Society, November

5, 1891, I presented a case of appendicitis to illustrate our tre.itment of the incision. Buried sutures of silver wire had been used to bring together the cut edges of the abdominal muscles, and an uninterrupted buried suture of silver wire closed the wound in the skin. The latter suture h.id already been withdrawn and a fine pink line indicated \vhere the skin incision had been made. A little below the centre of the wound was the orifice of a sinus from which a narrow strip of gaure had just been removed. The cicatrix was three weeks old.

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JOHNS HOPKINS HOSPITAL BULLETIN.

[No. 43.

each other, and to the underside of the lips of the open part of the wound. The thickness of this membrane depends principally upon the length of time that the gauze is allowed to remain undisturbed. I have found it so strong after ten days that I could with difficulty thrust my finger through it. This membrane atrophies in time. After two years I have found the walls of a sinus to the gall bladder attenuated to little more than a trace.

With our present resources it is not justifiable to attempt to disinfect an abscess cavity of the peritoneum, no matter how infiuitesimally small this abscess maybe. Bull and two others, whose names I am not at liberty to mention, are probably not the only ones who have furnished disastrous instances of such attempts.

In operations for appendicitis we have always the strangulated stump of the appendix and usually tissues more or less necrotic in its immediate vicinity as a complication. My experiments* demonstrated conclusively the result of inoculation of strangulated tissues in the peritoneal cavity.

The problem is a very different one when we have an abscess in the cancellous tissue of bone or in highly vascular soft parts to deal with. We may safely close such abscess cavities. If, for example, the so-called pyogenic wall of an abscess in muscle is excised and the parts are then thoroughly washed with an antiseptic solution, we may so far inhibit the pyogenic organisms that the tissues or, if there is a 'dead space, the prolific granulations, assisted possibly by the blood, may altogether destroy them. In the cancellous tissue of bone a cavity large enough to hold a hickory nut becomes completely filled with granulations in about three days. Blood clots occupying such cavities, if inoculated with virulent cultures of staphylococcus aureus, rarely break down. As a rule, the so-called organization of the clot takes place in from two to four days without suppuration. But an abscess in the peritoneal ca\ity is a very different affair because (1) the wall of the abscess consists in part of strangulated or more or less necrotic tissue which we cannot excise; (2) attempts. to disinfect such an abscess would probably be futile and might be worse than futile; (3) failure to disinfect might mean general peritonitis and the death of the patient, and not merely the retardation of healing.

There cannot be a definite incision for appendicitis. In general, if there is a large abscess, the incision should be made as near as possible to the crest of the ileum, so as to diminish the chances of entering the clean peritoneal cavity and to lessen the possibility of a hernia. The muscles are thick in this region, and when divided offer broad surfaces for coaptation by suture; and if the incision is too close to the ileum to admit

• The Johns Hopkins Hospital Reports. Report in Surgery, I.

of suture there is little danger of hernia resulting, as we know from a long experience with psoas abscesses, which we open by preference in this region. But the position of the abscess or, if there is no i^us or too little pus to be detected, the position of the appendix in the given case should determine the site of the incision. If there is an abscess the tissues over it should be most carefully studied as they are being incised for signs of infiltration with inflammatory products. A little oedema of the deeper muscles (transversalis or internal oblique) may guide us to a circumscribed spot of adhesion of caecum or omentum to parietal peritoneum and enable us to empty a large abscess without entering the uninfected part of the peritoneal cavity, or to thoroughly protect the intestines about the encapsulated pus cavity from the danger of infection before the pus is liberated. AYe place several yards of gauze between the healthy intestines and the abscess before opening the latter.

From a bacteriological point of view, we must often, if not always, inoculate the healthy peritoneum, but thus far we have not in a single instance had peritonitis supervene upon an operation for appendicitis, nor have we a single death to attribute to the operation. In the case of a large abscess, which we have evacuated without entering the uninfected peritoneal cavity, we still hesitate to search for and remove the appendix if its removal would necessitate our entering the clean peritoneal cavity.

When there is little or no pus to be discovered we make our incision directly over the appendix, which can usually be palpated. Here, too, we try to cut through thick muscles if possible. The instant that the peritoneum is opened, and before it is widely incised, v>'e introduce large towels of gauze, and with these press the intestines over the appendix out of the way and towards the left. AVhen the appendix is nicely exposed and a clear field for operation obtained, we introduce more gauze to serve as an inner lining to the outer ring of gauze. The adhesions which bind down the appendix are then slowly broken up by gentle finger pressure, and if pus is present it is caught as it leaks out by additional gauze sponges. If the iuner layer of gauze packing should by accident become soiled it is immediately replaced by fresh packing, the opening into the abscess being meanwhile stopped with a gauze sponge. And so, little by little, the abscess is emptied, and finally the appendix removed. After ligating the appendix and its mesentery we may excise the mucosa which is cut off by the ligature. We never sew up the end of the stump in the infected cases, as some surgeons have advised. This would be a foolish waste of time ; for the circulation of the part stitched has been cut off by the ligature applied to the appendix. The gauze for packing is rubbed full of a mixture of iodoform and bismuth and then sterilized.

THE JOHN'S HOPKINS HOSPITAL REPORTS.

Volume IV, No. 6 (Report in 8urgei*y II), !N"o\v Ready.

Contents: The Results of Opekatioxs for the CritE of Cancku of the Breast, performed at the Johns Hopkins

Hospital from June, 1889, to January, 1894.

By WM. S. HALSTED, M. D., Profensor of Surgery, Johns Hopkins Univerrily, and Surgtonin-Chitfto the Johnu Hopkins Hospital.

Price, $1.00.

Address Thk Johns Hopkins Pkkss, Balti.mure, Mu.

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

115

THERAPEUTIC USE OF EXTRACT OF BONE MARROW.

By John 8. ]}illixgs, Jr., Assistant Resident Physician. {Head before the Johns Hopkins Hospital Medical Society, .November 5, 1894.)

The use of bone marrow in cases of anaemia and in certain diseases of the blood-making organs was probably suggested by the success of the treatment of myxcedema with thyroid extract. The marrow is thought by most authorities to be the principal seat of formation of the red blood corpuscles. A diminution in number of the red corpuscles may be due to increased destruction or to diminished formation, and it was hoped that in either case the administration of the marrow as a medicine would stimulate the blood-making organs to increased activity, and thus make up the loss in red corpuscles.

The first case of anaemia treated in this manner was reported by Fraser.' A diagnosis of pernicious anaemia was made, based upon the histoi-y of the case, the number of red corpuscles and per cent, of haemoglobin, and the poikilocytosis of the red corpuscles. No mention was made as to the occurrence of nucleated red corpuscles, the presence of which in the blood in pernicious anremia being a point upon which Ehrlich lays considerable stress. The case was given bone marrow with arsenic for the first two months, then bone marrow alone for a month, and finally bone marrow and iron for three months. In the first two months the corpuscles rose from 1,006,000 per cmm. to 4,000,000, ranging at the latter point until discharge, four months later.

Bigger' reports a case of leucocytheemia in a boy, which was treated with the bone marrow. There was rapid diminution in the size of the spleen and marked improvement within a week. No mention is made of any examination of the blood, and it is possible that the case may have been one of splenic ana?mia or of the pseudoleukaemic infantile anfemia of Von Jaksch.

Danforth' reports a case of pernicious anajmia apparently cured by the use of bone marrow. Here also the report of the blood condition is incomjilete, as only the number of red corpuscles and per cent, of haemoglobin are stated. The latter rose from 35 per cent, to 80 percent. The bone marrow in this case, as in that of Fraser, was given in combination with arsenic.

In our own cases the marrow was given in the form of a glycerin extract which was prepared in the following manner. Twelve sheep's ribs, carefully scraped, were chopped into small fragments and rubbed up in a mortar with one pound of glycerin. This was allowed to macerate for three or four days, being kept in a refrigerator during that time. It was then strained through gauze, and the resultant liquid administered in teaspoonful doses three times a day. No complaint was made by the patients with regard to its taste.

Case 1.— Chlorosis. Girl, aged 20 ; admitted June 21, 1894, complaining of dyspnoea and weakness. Past history was negative. Present illness of four niontlis' duration. Physical examination

' Brit. Med. Jour., June 2, 1894. 'Lanoet, September 22, 1894. 'Chicago Clin. Review, IV, 1894.

showed nothing beyond marked anamia, and a loud functional murmur along the left sternal margin.

Blood count on admission, reds 2,898,000, whites oCOO ; haemoglobin 32 per cent. Stained specimens of the blood showed nothing beyond the pallor of the centre of the red corpuscles, so characteristic of chlorosis. No treatment was instituted for the first ten days, i. e. until July 1st, when the extract of bone marrow was begun. The blood count at that time was, reds 3,198,000, whites 5500 ; hfemoglobin 38 per cent. The extract was discontinued July 16, as patient insisted on leaving the hospital. The blood count on the morning of discharge was, reds 4,192,000, white 7000; hemoglobin 40 per cent. She was given Blaud's pills, and subsequently did well.

Case 2. — Chloro-anoemia in a boy. Past history was negative. For a month had complained of headache and gradually increasing weakness. Inspection showed a moderate grade of ansemia, physical examination being otherwise negative. On admission the blood count was, reds 3,290,000 per cmm.; haemoglobin 35 per cent. Stained specimens of the blood showed nothing beyond the pallor of the centre of the red corpuscles. Such a blood condition in a young female would certainly lead to a diagnosis of chlorosis, but the diagnosis of chlorosis in the male is always hazardous. The extract of marrow w'as ordered, and the condition of the blood gradually improved, the red corpuscles reaching a normal point (5,000,000 per cmm.) in about a month. The hfemoglobin rose more slowly, and on discharge (see chart 3) was only (38 per cent. As a rule, in chlorosis we must be satisfied if we can get the basmoglobin as high as 75 to 80 per cent.

Case 3. — Pernicious anaemia. Man, aged 51, admitted Jnne 15, 1894, complaining of vomiting and progressive weakness. He was very pale, and had first noticed the pallor ten weeks before. Had not lost very much in weight. Inspection showed a marked grade of ansemia, with the lemon-yellow discolorization of the skin so frequently seen in pernicious aniemia. Physical examination and examination of the stomach contents were negative. The case was at first suspected to be one of cancer of the stomach, but the absence of tumor, the readiness with which the gastric symptoms yielded to treatment, and finally the condition of the blood, all pointed to its being a case of the idiopathic ana;mia of Addison, th£ so-called primary pernicious anemia. Blood count on admission, reds 1,148,( 00, whites 4400 ; bsemoglobin 27 per cent. By July Ist the red corpuscles had sunk to 918,000, and the htemoglobin to 17 per cent. Stained specimens showed marked poikilocytosis and polychromatophilic staining of the red corpuscles. Several nucleated red corpuscles seen, the greater number being normoblasts. The remainder were typical megaloblasts, w^ith large pale nuclei and polychromatophilic protoplasm. Many micro- and megalocytes. A differential count of the leucocytes showed the per cent, of the small mononuclear forms or lymphocytes to be increased to 34 per cent., almost twice the normal. This technic.il description of the blood condition is given to show the grounds on which the diagnosis was based. The absence of any .npp.irent causative factor, and the fact that the per cent, of hjemoglobin was relatively higher than that of the red corpuscles, confirmed the diagnosis. The use of the extract of bone marrow was begun June 30th. At fiist the blood condition improved, the red corpuscles rising to 1,400.000. They fell again to 970,000, however, and the extract was discontinued July ISth, it having been given 19 days without causing improvement. Fowler's solution was ordered in increasing doses, and the patient gradually improved, being discharged October 12th in fairly good condition. Blood count on discharge, reds 3,(5C0,lC0, whiles 7C00 ;

red corpuscles. 'BroHtn=^\ia:mrnjlohin. = colo?le««(

No. 1. J. K. Pernicious An;emia. Case 3.

liKmoglobin C9 per cent. Stained specimens showed no poikilocytosis, no nucleated red corpuscles, and the per cent, of the various forms of leucocytes was normal. (See chart 1.)

Cau 4.— Pernicious antcmia. Man, aged 6.5, admitted August 15, 1894, complaining of weakness and shortness of breath. Illness began about one year before admission, and has been gradually progressive ever since. Has lost very little weight. Physical examination negative beyond a marked grade of ancemia Skin distinctly lemon-tinged. The urine was high-colored, but of low specific gravity, a condition which has been frequently observed in pernicious anromia, and whirh is supposed by Hunter to be due to the presence of pathological urobilin in the urine. The recent investi

gations of Hopkins (Guy's Hosp. Rep., 1893) would seem to make the existence of this substance improbable. He found only normal urobilin and hxmatoporphyrin in the urine in pernicious anremia. Blood count August 18, reds 2.048,000, whites 5000 ; hicmoglobin 45 per cent. Stained specimens showed a moderate grade of poikilocytosis, such as is seen in severe secondary anivmia. No nucleated red corpuscles. Percentages of leucocytes normal. The number of red corpuscles gradually sank, and between September 8th and October 6th ranged between 1,120,000 and 1,392,000; during this time patient was taking Fowler's solution.

Stained specimensof the blood taken September2d showed marked poikilocytosis, many micro- and megalocytes and many polychro

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN

Blac7c = red corpuscies. Brokctt= hminonlohiii. - ■ No. 2. J. R. Pernicious Anaemia.

- ^ co/or/c-w corpuscles. Cask 4.

matophilic red corpuscles. A relatively large number of nucleated red corpuscles were seen, 80 per cent, of which were typical megaloblasts, the remainder being normoblasts. A differential count of the leucocytes showed the lymphocytes to be distinctly increased (26.5 per cent.). On October (ith the blood count was, reds l,3-)8,000, whites, 30no ; haemoglobin 31 per cent. Up to this time the patient had had two courses of Fowler's solution, but the physiological limit of the dose had not been readied. On October 10th the extract of bone marrow was ordered, the blood count next morning being, reds 1,550,000, whites 3500; haemoglobin 35 per cent. The marrow was continued for two weeks, .luring which time the patient failed visibly, the red corpuscles sinking to 822,000 ; heemoglobin 18 per cent. On October 27 the extract was discontinue! and Fowler's solution in increasing doses was ordered.

Stained specimens of the blood, taken on Oct. 27th, showed an interesting state of things. While the poikilocytosis. or deformity in shape and size of the red corimscles, was markedly increased, the nucleated reil corpuscles had almost entirely disappeared, only one megaloblast being seen in four specimens. Such a disappearance of the nucleated red corpuscles from the circulation may be interpreted in two ways: either the blood condition has improved to such an extent that great activity on the part of the bloo<i-making organs is no longer necessary, or it has deteriorated so much that new formation is no longer ]>ossible. The latter condition obtained in a case of fatal purpura h.-emorrhagica rejwrted by the writer in the John.i Uopkim JfoajiiUit J5iill<!tin. May, 1894. Ehrlich has also reported two cases. In the present case this was also the condition that probably prevailed. Blood count Nov. 3d, reds

n

'

t

(

90.000

18,000

H,000

14.000

d on Nov. 3d showed about the same condition of things as on Sept. 2d. The differential count of the leucocytes is so typical that it will be given in full :

Large. Polynuclears. Lymphocytes, mononuclears. Transition. Eoslnopliiles. 52.1 per cent. 32.2 per cent. 2.4 per cent. 4.2 per cent. 6.1 per cent.

Nucleated red corpuscles again appeared in the blood in relatively large numbers, 59 being seen while making a differential count of 500 leucocytes.* This reappearance of the nucleated red corpuscles

may be taken as a relatively favorable sign, showing that the bloodmaking organs are once more active. If improvement occurs in this case under the use of arsenic it will be slow, as it requires some time to safely increase the dose to the physiological limit (20 to 25 min. t. i. d.). The general record of the case is given in chart 2.t

• This Is a very convenient mode of expressing tUc number of nucleated red c»v|iiisc1e8 pro.ipnt In n specimen of blood, but wo must always take Into vonsiilcraticin tlie numlicr of leucocytes per cmm. For example, suppose case

A shows 2000 leucocytes per cmm., and case H flUOO. Now while making B difTcrentinl count of 500 leucocytes in a stained specimen from A we see 12 nucleated reds, in a similar count in a specimen from case B we see only * nucleated reds. Yet the number of nucleated red corpuscles in the blood is about equal in the two cases, as in case B we cover only one-third of the ground that we do in case A.

tSincc the above went to press this imtlent has died. A final blood couut on Nov. 16, made SI hours before death, showed only 700,000 reds, 1000 whites: hiemoglobin 17 per cent. No autopsy.

November, 1894.]

JOHNS HOPKINS HOSPITAL BULLETIN.

119

It will be seen that the two cases of chlorosis were benefited by the use of extract of bone marrow, while the two cases of pernicious aufemia were unimj^roved. It is difficult to understand how this remedy could be of service in cases of pernicious anaemia. Its effects can hardly be considered as analogous to those produced by thyroid extract in myxoedema. In the latter case there is atrophy of the gland, giving rise to defective secretion, so that there is an indication for attempting to supply this defect by the administration of thyroid extract. But the marrow in pernicious anemia is, if anything, in a state of hypertrophy, and the condition is far more analogous to that of the hypertrophied and supposedly over-active thyroid glaud in exophthalmic goitre than to that of the atrophied gland in myxosdema. Besides, there is no proof whatever that the marrow acts as a gland in the ordinary sense of the word. The formation of red blood corpuscles by the bone marrow cannot be properly termed a secretion, it being rather a process of cell multiplication and development, and there is no proof that this process is influenced in any way by any chemical product of the marrow itself. As regards the cases reported by previous observers, two things may be noted.

First, there is room for doubt that they were true cases of pernicious anaemia. Second, the patients were given arsenic together with the bone marrow. ISTow it is well known that some cases of pernicious ansmia do remarkably well on arsenic, and several instances of apparent cure have been reported. Such an improvement is shown in Case 3 of our series.

It is different as regards the use of bone marrow in chlorosis. The marrow contains iron in considerable quantity, and we may reasonably suppose that the glycerin extract' contains sufficient iron in organic combination to be of service in chlorosis, a disease which yields so readily to iron in almost any form. Whether its value in such cases is greater than that of the various forms of iron used in medicine is doubtful. This is well shown in chart .3, where a blood chart of a case of chlorosis treated with Blaud's pills is given together with that of Case 2 of our series. The former does not suffer bv the comparison. The conclusion is that the extract of "bone marrow may be of value in cases of ordinary ana?niia and chlorosis, such as would be benefited by iron in other forms, but that there is no proof of its being of value in cases of primary pernicious ansemia.

PROCEEDINGS OF SOCIETIES,

THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of October 1, 1894. Dr. Kelly in the Chair.

Prof. J. J. Abel was elected Chairman for the coming year, and Dr. J. G. Clark was made Secretary.

Prof. W. D. Miller.of the University of Berlin, delivered an illustrated lecture in the amphitheater before an audience of Baltimore physicians and dentists, on "Some Points in Oral Pathology in Relation to Diseases of the Associated Parts and to general Diseases."

Meeting of October 15, 1894. Dr. Abel in the Chair. Case of Hereditary Chorea.— Dr. Osler.

Dr. Osier presented the case as illustrating a somewhat unusual feature in the family form of chorea, namely, the onset at a comparatively early age.

F. T., aged 28, a native of North Ware, N. H., was admitted Oct. 6, 1894, complaining of nervousness.

His father died at 59, after an illness of two weeks' duration. His mother died when 49 years old, of a disease similar to that with which he now suffers. She had nervous twitching for as long as he can remember. The trouble grew gradually worse, so tluit she could not move from her cliair and she finally became bedridden. He does not think that any other members of his mother's family were affected. He has liad four sisters and two brothers. One brother died at the age of 32, of inlluenza, afier he hail Iwen .afllicted for eight years with the .same sort of disease as the mother. The other brother and the sisters are well and strong and have no muscular twitchings.

Personal History. As a child he had the usual disorders, but he was very well and strong until the eighteenth year. He had a comfortable homo upon a farm, and though of a nervous temperament and troubled with weak eyes at times, he remained very well. He had an accident to the right elbow when he was fifteen years

of age. When seventeen he had occasional rheumatic pains in the joints, but which never kept him from work. He has never had gonorrhoea or syphilis.

The present trouble began when in his eighteenth year. It was first noticed as a very slight twitching of the arms and hands. The movements afterwards involved the other parts of the bodv— face, shoulders and legs. He thinks the latter were involved about eight months after the arms, and a little later the muscles of the face. The twitchings have persisted uninterruptedly to the present time. He has been able to work, however, until July of last year, but the involuntary movements now interfere with his doing manual labor. In 1888 he went to California for his health, having been troubled with a cough.

NOTES ON NTEW BOOKS.

BULLETIN

OF

THE JOHNS HOPKINS HOSPITAL.

Vol. V.-Nos. 44-45.

BALTIMORE, DECEMBER, 1894.

+++

Contents

A Contribution to our Knowledge of Organic Sulphur Compounds in tlie Field of Animal Chemistry. By Joun J. Abel, M.D., 123

A Case of Paranoia, with a Study of the Cerebral Convolutions. By Heney J. Berkley, M. D., 130

Angio-Sarcoma of the Ovary. By Thos. S. Cullen, M. B., - 134

Proceedings of Societies :

The Hospital Medical Society, 136

Exhibition of Specimens from a Case of Deciduoma Ma

lignum [Dr. J. Whitridge Williams] ; — The Best Method of Sharpening a Microtome Knife [Dr. Lotsy] ; — Ureterotomy [Dr. Kelly] ; — A New Method of exploring the Rectum and Sigmoid Flexure [Dr. Kelly] ;— Double Castration for Hypertrophy of the Prostate Gland [Dr. Finney].

Notes on New Books, 138

Books Received, 140

Index to Volume V, 141

A CONTRIBUTION TO OUR KNOWLEDGE OF ORGANIC SULPHUR COMPOUNDS IN THE FIELD OF ANIMAL CHEMISTRY.^

By John J. Abel, M. D., Professor of Pharmacology. {From the Pharmacological Laboratory of the Johns Hopkins University.)

It is well known to workers in the field of aniuiiil chemistry that when freshly voided dog's urine is shaken up with milk of lime, or is made thoroughly alkaline with sodium or potassium hydrate, a peculiar, penetrating, offensive odor is developed ; but beyond the merest passing references, nothing can be found in literature regarding the compound yielding this odor, and nothing seems to have been done toward determining its nature. Thus,' Biihrn and Lauge, discussing the applicability of Schlosing's method to the determination of ammonia in the dog's urine, remark that the addition to the urine of milk of lime gives rise to a peculiar, penetrating, garlicky odor, filling the whole bell-jar even after the lapse of 48-72 hours. V. Knieriem ' makes a similar reference, but no one has gone farther than to note the presence of this odor.

' The substance of a paper with the title : " On the occurrence of ethyl sulphide in the urine of the dog; on the behavior of ethyl sulphide dissolved in concentrated sulphuric acid toward oxidizing agents, and on certain reactions for llio detection of alkyl sulphides," appearing in the December number of the Zeilschr. f. physiol. Chemie.

'Archiv f. exp. Pathol, u. Pharmakol., Bd. 2, p. 368.

»Zeitschr. f. Biol., Bd. X, p. 2l>9.

There .ire many substances known to chemistry which may be said to have a penetrating, offensive, stupefying, and in some cases, garlicky odor. Among these are the mercaptmis, the organic sulphides, selenides and tellurides, the phosphines and the isocyanides, but in the present instance no help was derived from tlie smell in identifying the body, as no one whose judgment was asked in the matter could state positively that the odor was like lUiy other known to him.

I was obliged to direct my first efforts toward gaining some notion of the ultimate qualitative composition of the body. To this end I proceeded as follows: Air from an ordinary large glass gasometer was made to bubble through two liters of urine to which about 100 cc. of thick cream of lime had been added, and the whole thoroughly agitated for a few moments, and this air, laden with the odorous substance, was forced through an empty wash bottle, then through two Muencke's wash bottles made entirely of glass, each containing a 10 per cent, solution of hydrochloric acid, then through two similar wash bottles filled with a 40 per cent, solution of sodium hydrate, then through an empty Kettle, and then through a piece of combustion tubing 60 centimeters long, filled in its middle third with asbestos fiber which had preri

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oiisly been heated piece by piece to a white heat iu the flame of a l^arthel's alcohol blast-lamp. Pure oxygeu taken from an Elkan's cylinder and well washed by being made to pass through both acid and alkali, was forced into the tube containing the purified asbestos at the point where the air laden with the odoriferous body entered it.

From the tube filled with the asbestos the current of air was next passed into a Geissler potash bulb half filled with a 2 per cent, solution of the purest hydrate of sodium. With the ap})aratus arranged as described, the combustion tube containing the asbestos was kept at a red heat in a short four-burner furnace for five hours, the air and oxygen passing at about the rate that is usual iu combustion analyses.

At the end of this time a portion of the sodium liydrate solution in the Geissler bulb was acidulated with hydrochloric acid and tested with a few drops of a solution of barium chloride, with the result that an immediate precipitation of barium sulphate occurred. It may here be noted that the air current after it had passed the heated tube turned a blue litmus strip red, whereas it had no action on litmus before being heated, thus demonstrating that the sulphur of our conij)Ound had l)ecn turned from a neutral into an acid combination. A blank experiment in which the urine was replaced hv distilled water was carried on for six hours, but in this case the sodium hydrate yielded no trace of sulphate. Our conclusion must therefore be that the volatile, odoriferous compound contains sulphur.

At this point two questions present themselves: First, can this sulphur compound be referred for its origin to the action of the hydrate of calcium upon one of the known so-called ' " neutral " sulphur compounds of the urine, such as cystin and allied compounds, or such as hyposulphurous, sulphocyanic or mercapturic acids ?

Second, does the air after passing through the system of wash bottles used in the combustion experiment, contain any other substances than this odoriferous compound 'i

The first question can be answered with considerable certainty by the method of exclusion. Cystin does not seem to be decomposed by treatment with milk of lime at room temperature. Baumann and Brenziger ^ have shown, however, that when ethyl cystein is heated with a free alkali, ethyl mercaptan is split off. M. v. Nencki' was the first to demonstrate that the nausesiting odor of the urine after asparagus has been eaten is due to methyl mercaptan, and also that methyl mercaptan is one of the products of the bacterial decomposition of proteids.' Karplus' has also found methyl mercaptan in the urine as the product of a special bacterium, and L. v. Nencki ° finds that it is always present among the gases of the large intestine. Because, then, of the proved occurrence of mercaptjms in animal fluids, one cannot neglect making the proper tests for them where an offensive, not strictly definable odor is

'Salkowski : Archiv f. path. Anat. u. Physiol., Bd. 58, p. 472. 'Zeitschr. f. physiolog. Chem., Bd. 16, p. 565. "Archiv f. exp. Pathol, u. Pharmakol., B.l. 28, pp. 200-209.

• M. v. Nencki and N. Sieber: Monatsli . f . Chemie, Bd. 10, pp. 52G-31 .

'Archiv f. pathol. Anat. u. Physiol., Bd. 131, pp. 210-222. •Sitzb. d. kaia. Akad. in Wien, Mathum. Classe III, Abth. 98, pp. 437-8.

met with. But in the case under consideration the making of such tests will be seen to be unnecessary, for the very process of setting free our odoriferous compound with alkalies would have bound the mercaptans and prevented them from leaving the bottle, and an impassible barrier would also have been found in the wash bottles filled with sodium hydrate.

As for the other neutral sulphur compounds of the urine, the acids above mentioned, it may be remarked that the calcium and alkali salts of at least one of them, sulphocyanic acid, is stable and therefore could not come in question. The alkali salts of hyposulphurous acid are readily soluble and stable; the calcium salt is equally soluble but unstable.

Now, to exclude hyposulphurous acid as a possible source of the sulphur found in our combustion experiment, we have only to state that this experiment yielded the same result when fixed alkali instead of milk of lime was used to free the odoriferous substance. But even with the employment of calcium hydrate it seems hardly possible for sulphur dioxide to escape from a fluid containing such an excess of lime.

As to the mercapturic acids being a possible source of our sulphur compound, we have only to note Baumann's ' discovery that when they are decomposed with alkalies mercaptans are split off, a fact that has been adopted into the methods of urinary analysis. But we have demonstrated that it would be impossible for a mercaptan to pass over into the combustion tube. A further proof that excludes both the mercaptans and also sulphureted hydrogen is seen in the fact that two strips of filter paper moistened with alkaline lead solution and placed, the one between the bottle of urine and the first wash bottle, and the other between the last wash bottle and the combustion tube, never showed the slightest change of color.

It is therefore fair to conclude that our sulphur compound is not a derivative of one of the known " neutral " sulphur compounds of the urine, but that it is split off by the milk of lime from a still unknown sulphur compound of the urine.

We now turn to the second question : Does the air after passing through the system of wash bottles used iu the combustion experiment contain any other substance besides this odoriferous compound ? If we bear in mind the contents of the series of wash bottles, it will be seen that no substance with acid or basic properties could have passed them ; in other words, that only a chemically indifferent substance could have been found with the sulphur compound at the end of the series of bottles. This disposes not only of the mercaptans, but of all the various compounds spoken of in the beginning as having an odor similar to the compound in question, with the sole exception of the organic sulphides."

The phosphines, too, are excluded, for, being basic substances,' they would be held back by the hydrochloric acid. Then, too, the phosphines are very readily oxidized, and in

' Baumann : Zeitschr. f. physiolog. Ch., Bd. 8, p. 194.

■The selenides and tellurides are obviously out of theciuestion as constant products of animal metabolism, but see a late interestinfi paper by F. Hofmeister in Arch. f. exp. Pathol, u. Pharmakol., Bd. 33, p. 198, on the ability of the organism to form the nauseating methyl telluride and selenide on the introduction of selenium and tellurium or the salts of their acids.

" With the exception of the primary phosphineB.

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sniiill amoniits could not be made to bubble np through so many wash bottles without being destroyed by this long contact with the air. A long series of experiments was, in fact, undertaken to determine whether or not a volatile phosphorus compound was present along with the sulphur eoniponnd before it was washed, but all with negative results.

It therefore seemed fair to assume that our sulphur compound was the only substance carried by the air through the series of wash bottles, and all the subsequent experiments made to establish its identity furnish additional support for this assumption.

SOLUTION OF THE COMPOUND IN CONCENTRATED SULPHURIC ACID, AND PROPERTIES OF THIS SOLUTION.

A series of experiments was next undertaken to determine how this sulphur compound could be collected in suiBcient quantities for study and analysis. It was finally found that concentrated sulphuric acid completely absorbed the body and the resulting solution is without color and also without odor unless the air current is allowed to bubble through the sulphuric acid for several days, when a faint oniony smell is perceptible. In concentrated sulphuric acid we have then a means of storing considerable quantities of this sulphur compound.

Chapman suction pumps were used to draw air through large flasks containing urine and milk of lime, then through two wash bottles containing a 10 per cent, solution of hydrochloric acid, then through two wash bottles filled with a 40 per cent, solution of sodium hydrate, then through a U tube 12 inches high and 1 inch in diameter filled with pieces of potassium hydrate, then through two similar TJ tubes filled with granular calcium chloride, and from this last tube the air hiden with the sulphur compound passed through a Geissler bulb or through a small wash bottle containing concentrated sulphuric acid. The connections beiween the bottles were glass to glass held in place by the best black English tubin<r Iwo such circuits were usually kept at work bv the same suction pump, and the pump was operated day and night -Vfter about 72 hours, in which time 1.5-30 liters'of dog's urine had been exhausted of the sulphur compound, the (Jeissler bulb containing sulphuric acid was replaced bv another. On diluting with water some of this concentrated sulphuric acid hat has been charged with the body, or on neutralizing it with ree alkalies, or on the addition of almost any metallic salt at hand, an intense odor like that of one of the organic sulphides pervades the room. These properties of dissolvincr i„ considerable quantities in sulphuric acid and of formino- ^vith it a nearly or quite odorless solution, and of being^set free unchanged on dilution with water or on neutralization of the su phuric acid, are possessed, so far as I know, bv the sulphides' only among organic sulphur compounds. I have repeatedly dissolved 10 or 12 grams of ethyl sulphi.le in 100 cc. of concentrated sulphuric acid, having previously cooled both fluids and found that the resulting solution had no odor whatever but^i^idduigjo this solution half its weight of water, or,"

'In all probability, however, the analogous seleni.les and telh.rIdes behave in the same way toward concentrated sulplinric acid.

better still, of ice, the ethyl sulphide soon appeared floating on the top of the diluted sulphuric acid. Dimethyl sulphide and methyl ethyl sulphide were found to behave in the same way. Reference books on chemistry do not mention this property, and It was only after the completion of mv experiments that I learned that this method is employed in refining crude Ohio petroleum, and that Mabery and Smith ' had by it= help recovered alkyl sulphides from the "distillates of crude petroleum."

OXIDATION OF THE URINARY SULPHIDE.

The alkyl sulphides arereadily oxidized to the fluid sulphoxides, and then further to the very stable crystalline sulphones. Ihus, if ethyl sulphide, (CJUS, is oxidized with nitric acid specific gravity 1.2, ethyl sulphoxide, (aH;;,SO, is produced, a thick, unstable fluid, easily soluble in water. If. however, fuming nitric acid is used, then diethyl sulphone, (C.H,),SoJ results, which crystallizes in large rhombic plates vefy soluble in water, melting at 70° and distilling at 248° without decomposition. The sulphoxides have the property of being reducible with zinc and sulphuric acid to the original sulphide. The sulphones, however, are very stable substances, unaffected bv treatment with zinc and sulphuric acid. It was hoped that oxidation of the concentrated sulphuric acid solution of the sulphide from the dog's urine with potassium permanganate would yield a sulphone, the composition and properties of which would determine which particular sulphide we were dealing with. Accordingly, about 100 cc. of a concentrated sulphuric acid solution containing the sulphur compound rallected from about 25 liters of dog's urine was treated in the following manner: A beaker containing it was placed in pounded ice, and from time to time were added a few drops of a concentrated aqueous solution of potassium permano-anate also cooled to 0° C. When the permanganate ceased to be decolorized, a cold 4 per cent, solution of sulphuric acid wa* slowly added until the acid in the beaker was reduced in strength to about a 20 per cent, solution. The whole was then heated on the wat«r-bath. while potassium permanganate was again added.

I'nder the influence of the heat an additional quantity of the permanganate was reduced, and the heating on the waterbath was kept up as long as any permanganate was decolorized.

The slight excels of permanganate, when reduction no longer occurred, was removed bv the addition of a little sodium formate.

The solution was then made alkaline with potassium hydrate, evaporated till crusts of potassium sulphate formed; the potassium sulphate filtered off, ajrain concentrated, again filtered, and now evaporated to dryness. The drv residue was extracted with a little absolute alcohol, half of thealcohol evaporated on the w ater-bath and the rest allowed to evaporate

' Americ. Chem. Journ., Vol. 13, p. 243, and Vol. 16, p. 3S. R. H. Smith h»s also treated ethyl fulphide with an equal hulk of strong sulphuric acid diluted with much waterand neutralized with barium carbonate for the purpose of forming barium-ethvl-hvposa!pbite, but makes no mention of the separation of the sulphide on dilution with water. Journ. of tlie Chem. Soc, 22 (1S69), p. 302.

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[Nos. 44-45.

spontaneously. A small quantity of a deliquescent compound remained. To remove all trace of potassium carbonate, the residue was extracted a third time with absolute alcohol and the alcohol again evaporated. On the addition of dilute sulphuric acid to some of the deliquescent residue, the odor of acetic. acid became very apparent. The characteristic odor of acetic ether was at once brought out on gently heating with the addition of concentrated sulphuric acid and alcohol, and the addition of ferric chloride to a neutral solution gave the characteristic blood red color of a solution of ferric acetate. These properties, viz., the deliquescence of the potassium salt, the odor of the free acetic acid and of its acetic ether, and the color of its ferric salt, leave no doubt of the occurrence of acetic acid as an oxidation product of the sulphur compound under examination. I was unprepared for this outcome, as I had hoped to secure a sulphone. On the supposition that a little of the sulphone might yet be mixed with the acetate, I acidulated its aqueous solution with sulphuric acid, drove away the acetic acid as far as possible on the water-bath, and again extracted the dry residue with alcohol, but only a trace of potassium acetate and sulphate was taken up. I now repeated the oxidation experiment twice over, making slight . variations in the method, such as the employment of finely powdered potassium permanganate instead of an aqueous solution, and sodium instead of potassium hydrate, yi the neutralization. 1 used also a little less than the necessary amount of permanganate, so as to avoid the after-use of sodium formate, but the iinal outcome was the same as before: an acetate again appeared.

A blank oxidation experiment was next undertaken in order to determine whether the reagents used contained any thing oxidizable to acetic acid, but not a trace of acetate was found.

We may therefore safely conclude that our sulphur compound contains one or two ethyl groups. It is not easy to draw conclusions as to the presence of a methyl group in the sulphide, as such a group would have been oxidized to carbon dioxide and water. Carbon dioxide is, in fact, given off when the acid solution and permanganate are boiled, but this can be referred to the destructive oxidation of some of the sulphide, for it also takes place when synthetically prepared diethyl sulphide is treated in the same way.

OXIDATION OF SYNTHETICALLY PREPARED ETHYL SULPHIDE UNDER THE SAME CONDITIONS.

It was now in order to compare the behavior of synthetically prepared ethyl sulphide with our sulphide. Accordingly, a preliminary experiment was first made as follows: Five grams of ethyl sulphide, which distilled at 91.9°-92° C, were dissolved in .50 cc. of sulphuric acid, and oxidized by adding small quantities of powdered permanganate very gradually to the concentrated sulphuric acid kept in a freezing mixture, an hour and a half being consumed in adding 12 grams. When too much was added at one time, a Hash of light would appear, showing that some of the sulphide was being completely oxidized, and the odor of ethyl sulphide also became apparent. 25 cc. of cold concentrated sulphuric acid were now stirred into the mixture, and from time to time

small portions of a concentrated aqueous solution of permanganate were added together with about 20 cc. of water. A colorless solution of an oniony odor now resulted and this was slowly diluted with water up to a liter, permanganate still being added. The solution was then boiled for a short time and as the permanganate was still being reduced, more was added. AVhen no more permanganate was reduced about 200 cc. of the fluid was distilled off. This distillate, which was plainly acid, was caught in a little strong potassium hydrate and subsequently enough more hydrate was added to give a neutral reaction, and it was then evaporated on the water-bath. There was obtained a small quantity of a deliquescent salt consisting of potassium carbonate and potassium acetate, which gave the reactions that we have already mentioned as sufficient to identify acetic acid. In a similar experiment it was observed that when the distillation was undertaken before the oxidation was complete, that is, at a time when the permanganate was still being reduced, the distillate had a most disagreeable odor, reminding one both of onions and of acetic acid. Also when evaporated to dryness with an alkali, it gives all the reactions of a sulphite, viz., it reduces permanganate, it yields sulphureted hydrogen on reduction with zinc and sulphuric acid, it decolorizes an iodine starch solution, it gives a red color to a weak solution of sodium uitroprusside, and it gives off the peculiar stinging odor of sulphur dioxide on acidulation with sulphuric acid. In such a case, therefore, one must first oxidize the sulphurous acid with permanganate before undertaking the tests for acetic acid or the preparation of one of its salts. When boiling is resorted to in order to hasten the progress of the oxidation, it is found that much carbon dioxide is given off. It is evident that in the above experiments the greater part of the sulphide was oxidized to the end products, sulphuric anhydride, carbon dioxide and water.

As, to my knowledge, the alkyl sulphides have hitherto only been oxidized to sulphoxides and sulphones, and not as in the manner indicated above, to acetic and sulphuric acids, it seemed worth while to attempt the quantitative oxidation of ethyl sulphide to these latter products. Accordingly, 12 grams were dissolved in 100 cc. of concentrated sulphuric acid, the latter being cooled in a freezing mixture; 65 grams of finely powdered permanganate, somewhat less than the quantity theoretically necessary to oxidize the sulphide to acetic and sulphuric acid, were then dissolved in 200 cc. of cold sulphuric acid, and this solution was slowly added to the cold solution of the sulphide. The permanganate was at first entirely decolorized and none of the sulphide was liberated or destroyed, but toward the end of the operation, as more and more of the oily heptoxide of manganese from the bottom of the beaker came to be added, the black mixture began to foam up, flames now and then shot forth and much carbon dioxide was given off. A repetition of the exi)eriment led to no better results. In both cases, however, water was added to the black, agitated mass, and after diluting to about a liter, the odor of acetic acid became plainly perceptible. When diluted to several liters and distilled, a little of the distillate treated as before gave all the tests for acetic acid. A little silver acetate was also produced which crystallized out of water in

December, 1894.]

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long, shiuing needles, gave off fumes of acetic acid, deposited silver on gentle incineration, and also emitted the odor of ethyl acetate on treatment with concentrated sulphuric acid and alcohol.

On account of the fact, however, that by far the greater part of the sulphide had been destroyed, it was evident that it would be useless to attempt the estimation of the amount of acetic acid produced. It would seem, therefore, impracticable to oxidize ethyl sulphide in this way with the intention of securing a large output of acetic acid, but any one can convince himself by an off-hand experiment that acetic acid IS one of the products of the oxidation of diethyl sulphide under the above circumstances. This is another point of agreement between the sulphide from dog's urine and ethvl sulphide.

What light this oxidation throws on the natureof tJie union existing between ethyl sulphide and concentrated sulphuric acid, and also whether thio-acetic acid may not be an intermediate product in the oxidation with permanganate, 1 cannot here discuss.

DOUBLE COMPOUND WITH MERCURIC CHLORIDE.

As the new sulphur compound from the dog's urine has so many points m common with ethyl sulphide, its behavior towards mercuric chloride was next examined.

Some of the concentrated sulphuric acid solution of the sulphide from the dog's urine was placed in an ice mixture and diluted with a cold 4 per cent, solution of sulphuric acid until the resultant liquid was equal in strength to about a 30 per cent, sulphuric acid solution. The odor found to arise from such large amounts of the diluted fluid was vei-y strong, and not to be distinguished from the odor of ethyl sulphide dissolved in concentrated sulphuric acid and treated in the same way. Indeed, none of the workers in mv laboratory could tell in any given case whether I was using the compound obtained from dog's urine or that svntheticallv prepared. The diluted solution of the sulphide was now shaken out with ether and the separated ether was washed twice with distilled water; an alcoholic solution containing 1 gram of mercuric chloride was then added to the ether and the whole evaporated to about one-third on the water-bath, after wliich It was allowed to stand in vacuo over sulphuric acid. The residue, which smelled strongly of the sulphide, was well washed on a filter with water in order to dissolve away the excess of mercuric chloride. It was then dried on the filter over sulphuric acid, dissolved when dry in a little alcohol and allowed to crystallize. Some of the crystals, long, slender in-isms mixed with some amorphous material were collected and their melting-point taken without further purification I his was found to be in one case about U5° C, and in another batcii of crystals prepared in a verv similar manner, ir>0° C. The noteworthy fact in both determinations was that the crystals melted to a black fluid, and after the capillary tubes had cooled, long slender prisms could be seen to stand out from the congealed drop.

I am personally convinced that this sulphide from the urine of the dog forms a double compound with mercuric chloride aUhough it must he a.lniitted tiiat Iho evidence, so far as it*'

melting-point is concerned, does not furnish conclusive proof that this compound is (CJi^\S.KgC\.

In support of this opinion that a double compound is formed, we may urge the odor of the compound, its insolubility in water, its solubility 'in alcohol, its behavior in the melting tube and its crystalline character. After standing over sulphuric acid /« vacuo, no odor, or at least onlv a very faint odor, is perceptible; but exposed to the air fo"r only" a few moments, the odor of the sulphide becomes very marked. The mercuric chloride compound of ethyl sulphide behaves in the same manner.

It is exceedingly difficult to separate a small amount of this unstable double compound, say a few centigrams, from an excess of mercuric chloride ; the various operations, such as the long and repeated washings with water, the necessary drying, etc., all involve so much loss of substance that sharj) results cannot be obtained when there is onlv little material on hand.

MELTING-POIXT OF THE DOUBLE COMPOUND (C,H.).S.HgCI,

The plan that was followed above in the attempt to secure and purify the double compound of ethyl sulphide from the dog's urine was based on previous experiments made in the same way with synthetically prepared ethvl sulphide. Five grams (boiling-point 91.9° C.) were dissolved in 50 cc. of concentrated sulphuric acid, and by following out the method described above, except that less of the theoreticallv required amount of mercuric chloride was used, the double compound crystallizing out of absolute alcohol in long, transparent. highly refracting prisms was obtained. This"^ recrvstallized out of alcohol, washed with cold absolute alcohol aiid ether, and dried in vacuo over sulphuric acid and paraffine, began to melt at 118° C. and melted to a coloriess fluid at 119° C. Subsequent recrystallizations out of ether caused no change in the melting-point. When the double compound is prepar^ by mixing alcoholic solutions of the sulphides and of mercuric chloride the melting-point is also 119°.

AVheu some of the finely powdered crvstals that show a melting-point of 119° are allowed to sbmd'over sulphuric acid forjiwo weeks, the melting-point is found to have risen to 131° C. Some of the unbroken crystals, however, that had stood for the same length of time over sulphuric acid melted at 120° C. When the temperature reached 180°-1S5° C. a rapid evolution of gas bubbles took place, but the liquid remained transparent and did not blacken.

Now Loir' gives 90° C. as the melting-point of cC^H.^S.HgCl, crystallized out of ether. An observation made bv me in'^the course of the above experiments may perhaps explain how Loir came to put the melting-point at 90° C. I prepared some of the ethyl sulphide mercuric chloride, recrystjillized it out of absolute alcohol, washed it with absolute alcohol and ether, and exposed it for half an hour to an air current produced by a Bunsen suction pump. At the expiration of this time the melting-point was taken and it was found that the substance melted at 80° C, yielding a perfectly transparent, colorless

'.\nn. il. Chem. u. riiarm. S7, p. 370.

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liquid. After standing for twelve hours over sulphuric acid in vacuo the melting-point was found to have risen to 119° C. It may be remarked in passing that Blomstrand ' finds one of Loir's melting-points, that of the platinum compound 2(C,H,.),S.PtCl„ 70° too low, it "being in reality 178° instead of 108° as given by Loir.

HEHAVIOK OF THE SULPHIDE TOWARD SOI.UTIOXS OF BROMINE AND IODINE.

It must be remembered that we- are confined to solutions of the urinary sulphide in concentrated sulphuric acid for a study of its properties. The behavior of bromine and iodine toward these solutions is characteristic and in every respect like their behavior toward similar solutions of synthetically prepared ethyl sulphide. If a drop or two of a 2 per cent, solution of bromine in potassium bromide be added to a sulphuric acid solution of the urinary sulphide, or to an equally weiik solution of ethyl sulphide, it will be observed that bromine is absorbed. The same thing is observed when bromine vapor is allowed to fall into a sulphuric acid solution that has previously been diluted with a few drops of water. If the sulphuric acid be poured off from the undissolved drop of bromine after having been thoroughly agitated with it, and then be diluted with water, it will be found that the sulphide odor no longer returns. If a piece of pure washed zinc and a litt>e more concentrated sulphuric acid be added, the sulphide odor returns as the reduction proceeds. A solution of ethyl sulphide of about the same strength as that from the dog's urine behaves in the same way. But if a strong solution be made, the absorption of bromine is very evident, for now considerable bromine may be added before some of it remains undissolved. Such a concentrated solution of ethyl sulphide treated with bromine still smells somewhat of the sulphide after dilution with water, but if left to stand for a few days the odor disappears, and may then be caused to reappear on reduction with zinc and sulphuric acid. We are in all probability dealing here with the bromine addition compound (Ci;H5)jSBr„, which, as described by Rathke," forms with water a colorless solution. Out of its aqueous solutions, iodine in potassium iodide precipitates an iodine addition product, (CJl5)jSI„ as a dark oily iluid.

Far more striking is the behavior of iodine, the study of which has led to a reaction which may under certain circumstances serve to indicate the presence of an alkyl sulphide. On the addition of a few drops of a 6-10 per cent, solution of iodine in potassium iodide, or of a ^^ normal iodine solution, an immediate precipitation occurs. The sulphuric acid solution becomes a dark brown, turbid fluid in which a precipitate of infinite fineness is suspended. After standing over night a small quantity of a dark brown oil separates out in minute droplets and settles to the bottom. This is undoubtedly the addition product (C,H*5)aSI,."

If the acid be poured off and water be added to this oily substance, the odor of a sulphide becomes at once apparent. The addition of a few drops of potassium hydrate immediately

' ' ,Tour. f. pract. Chem. (n. f.), Vol. 24, p. 190. 'Ann. d. Chem. u. Pharmac, BH. 162, p. 214. ' Kalhke, loe. rit.

causes the oil droplets to dissolve, and bringsout the sulphide odor in full strength. Iodine solutions also cause the dark cloudy precipitations in sulphuric acid solutions of the sulphides even when these are very much diluted with water, so that this reaction must be regarded as a very sensitive one.

Furthermore, a drop or two of the sulphide shaken up with much distilled water, say 60 cc, also gives a cloudy precipitate on the addition of a ^V^ormal iodine solution, and this precipitation occurs even when the aqueous solution has been allowed to stand for weeks, when we niily be sure that the ethyl sulphide is really dissolved and not merely suspended. Out of these aqueous solutions of the sulphide to which iodine solutions have been added, the oily product referred to also settles on standing. This last reaction demonstrates very clearly that ethyl sulphide, contrary to the usual statements, is by no means insoluble in water. I daresay that its solubility in water is fully equal to that of ethyl mercaptan.

Methyl sulphide and methyl ethyl sulphide behave in almost the same way toward solutions of iodine. The oily compound that is precipitated from dilute solutions of methyl sulphide in sulphuric acid seems, however, to pass again into solution on standing.

If to a distillate of dog's urine that has been shaken with milk of lime or made strongly alkaline with a free alkali, a few drops of an ^"^-iodine solution be added, a cloudy precipitation, very like that seen under the same circumstances in aqueous solutions of ethyl sulphide, will be observed. In this instance, however, the reaction is of uncertain meaning, for Schiff ' has shown that the distillate of the dog's urine contains a primary amine, and Abbott ' has found that aqueous solutions of amines give cloudy precipitates on addition of /^-iodine solution.

BEHAVIOR OF ETHYL SULPHIDE TOWARDS NITROUS ACID.

While trying to establish the identity of the sulphide treated of in this paper, I observed that when a drop of an aqueous 5 per cent, solution of sodium nitrite was added to some of the sulphuric acid solution of the sulphide from the dog's urine, the latter at once took on a beautiful deep green color. A drop or two of Liebermann's' nitrose sulphuric acid solution gives the same color and is preferable as a reagent to an aqueous solution of a nitrite, as if used in e.xcess it does not so readily cause the disappearance of the green color. The color persists for some time, but disappears if the solution is left to stand over night, and when the nitrite is not added in excess the reaction will be found to be of great delicacy.

To get this reaction with the urinary sulphide in perfection it is best to conduct the well-dried air and sulphide as

' Zeitschr. f. physiol. Chemie, Bd. IV, p. 54.

• Private communication from Dr. A. C. Abbott, of the hygienic

laboratory of the University of Pennsylvania, on the detection of amines in sewer air with N/20-iodine solution, which induced me to study the behavior of aqueous solutions of ethyl sulphide toward iodine solutions.

•• Ber, d. deutsch. chem. Gesellsch., Bd. 20, p. 3231 b. In making up the solution of a nitrite in cone, sulph. acid I used sodium instead of potassium nitrite.

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described on p. 135, with at least 5 or 6 liters of urine in the circuit, through a few cc. of concentrated sulphuric acid in a test tube an entire day. Special attention must be given to the drying of the air laden with the sulphide, for it is only when a completely dry current is passed into the concentrated sulphuric acid for the length of time named that a solution is obtained which will give at once the deep green color referred to, although solutions that have not remained so long in the circuit will also give a tinge of green, in which case, however, only a mere trace of the nitrite, such as adheres to a glass rod dipped into a solution of it, should be added. Now a drop or two of pure ethyl sulphide dissolved in a few cc. of concentrated sulphuric acid gives identically the same reaction on the addition of a drop or two of a nitrite solution or of nitrose sulphuric acid.

WHAT CHEMICAL CHANGES OCCUR IN THIS KEACTION ?

As long as the color persists, the sulphide can be liberated by the addition of small pieces of ice or by dilution with water, but after standing over night exposed to the action of an excess of the nitrose sulphuric acid, the now colorless solution no longer throws out the sulphide on the addition of ice. The reason for this is that the sulphide has been slowly oxidized by the nitrous acid to a sulphoxide, while the latter is reduced to nitric or niti'ous oxide. That this oxidation has occurred is demonstrated by adding a few pieces of zinc and allowing the reduction to continue for some hours and then diluting with crushed ice, when the original sulphide will again make its appearance. No further demonstration is needed to prove that the sulphide has been oxidized to a sulphoxide in the above exjjeriment. Since methyl sulphide and methyl ethyl sulphide also behave in the same way toward nitrose suljjhuric acid, it is fair to conclude that the reaction holds for the series of sulphides of the general formula

(C„H,„^,).« It might be suspected that the color reaction just described is due to thiophene formed on dissolving the sulphide in concentrated sulphuric acid, in analogy with the pyrogenous synthesis of thiophene first demonstrated by Kekule.' That we are not dealing with thiophene is, however, shown by the absence of that characteristic play of colors (green, blue to purple) that is always observed when a little nitrose sulphuric acid is added to a freshly prepared, sulphuric acid solution of thiophene, and by the fact that a solution of thiophene in concentrated sulphuric acid soon fails to give Lieberniann's reaction, in consequence of the rapid conversion of the thiophene into thiophene sulphonic acid. Then, too, that the green color described does not owe its origin to thiophene is proved by the fact that solutions of ethyl sulphide in concentrated sulphuric acid do not give the indophenine reaction, a reaction quite as delicate as Liebernuiun's reaction for thiophene.

The mercaptans, too, do not appear to give this reaction. As is well known, these sulphur compounds, when dissolved in concentrated suli)huric acid, are changed to the corresponding disulphides. Sulphuric acid solutions of ethyl mercaptau, the only one of the mercaptans that 1 have thus far

'See V. Meyer : Ber. il. ileutsch. chem. Gesell., Bd. 18, p. lilTa.

prepared for comparison, become murky and take on a reddish yellow color on the addition of a few drops of Liebermann's solution. The sulphides of the series C„Hj„S also fail to give this reaction.' Ethylene sulphide and propylene sulphide, when dissolved in concentrated sulphuric acid in small amounts, yield slightly green solutions. On the addition of a few drops of nitrose sulphuric acid the green color instantly disappears, giving place in the propylene solution to a 3-ellowioh turbidity, while the ethylene solution remains colorless. Methylene sulphide gives a colorless solution with concentrated sulphuric acid, which undergoes no change on the addition of the nitrose sulphuric acid.

It may be mentioned in conclusion that the vapor of pure ethyl sulphide was subjected to a destructive oxidation by passing it mixed with moist oxygen over asbestos heated to redness, exactly as described in the combustion experiment with the urinary sulphide in the early part of this paper. Here, too, the air that escaped from the combustion tube was laden with acid vapors, and an examination of the weak sodium hydrate solution in the Geissler bulb showed that sulphuric acid was present. When the supply of oxygen was insufficient, the bulb also contained sulphurous acid.

HAS THE SULPHIDE AN INTESTINAL ORIGIN ?

'J'he fact that methyl mercaptan is found among the gases of the large intestine,' and that there exists between ethyl mercaptan and ethyl sulphide a close relationship, suggests for the latter a possible intestinal origin, and that after absorption it unites with a compound that prevents its oxidation to end products and allows of its excretion in the urine. But an experiment in intestinal antisepsis' with calomel performed on a large well-nourished dog, showed after six days of abstention from all food except water and the administration of a total of 8 grams of calomel during the last three days, no appreciable diminution of the amount of the sulphide yielded to concentrated sulphuric acid. While this result is not absolutely conclusive because of the lack of quantitative methods for estimating the sulphide, and also because we cannot be certain that the bacterial activity in the intestines was completely suppressed, yet the evidence, so far as it goes, is against the bacterial origin of the sulphide. More conclusive is the negative outcome of all attempts to tiud the sulphide in the fseces of the dog by the use of the methods successfully applied to the urine.

The negative outcome of both experiments at least points to the probability.- that ethyl sulphide is a product of retrogressive metabolism. The urine, too, appears to contain decidedly more of the compound when the dogs are put ou an exclusively meat diet than when fed on the mixetl diet of refuse from the hospital kitchens.

So far as I have been able to discover, crude petroleum is the only other natural source besides the dog's uriue, of the

' This point was not established in time for its appearance in the German version of this paper.

' L. v. Nencki : Sitzb. d. kais. .\kad. in Wieu, Malhem. Classe III. Abth. 9S. 43:--13S.

■' Baumann : Zeiteohr. f. physiol. Chem., Bd. 10, 1SS6, S. 129.

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saturated alkyl sulphides. Now that we have methods for their detectiou, it is not unlikely that they will be found to be as widely distributed as are the mercaptaus. I hope soon to be able to offer something definite as to the properties of the compound from which the sulphide is liberated in the dog's urine on treatment with alkalis, and also to be able to isolate the pure sulphide in sufficient amount for the determination of its boiling-point, etc. It is only after having accomplished the isolation of the compound with which the sulphide is united that wc can say anything definite as to amounts in which the sulphide is excreted. Since, however, easily demonstrable quantities of sulphuric anhydride can be obtained by o.xidizing its vapor, one is justified in the opinion that it is present in equal or greater quantity than are such compounds as sulphocyanic or thiosulphuric acid. And it seems fair to conclude that it will be found on quantitative estimation to answer to the still uuideutified sulphur compounds in the dog's urine.

KKSUJIK.

It will be seen that the difficulties encountered in the collection and study of the new compound were not few. The following points have, however, been clearly established :

1. When dog's urine is treated with alkalies, an odoriferous compound is liberated which contains sulphur and which is taken up with avidity by concentrated sulphuric acid and from which it is again liberated on dilution with water or on neutralization. The odor arising during the progress of the dilution or neutralization is not to be distinguished from that of ethyl sulphide, (0,115)38. Ethyl sulphide is likewise absorbed by concentrated sulphuric acid with great avidity.

2. Oxidation of the urinary compound in the form of its solution in concentrated sulphuric acid yields sulphuric aud acetic acids, thus demonstrating the presence in it of an ethyl group. Oxidation of ethyl sulphide under the same conditions yields the same products.

3. Mercuric chloride forms with the urinary sul2)hide a double compound which behaves, as far as could be determined, in regard to odor, solubility and crystallization, like the corresponding ethyl sulphide mercuric chloride, (CaHJjS.HgClj.

■1. Bromine and iodine behave toward its solutions in concentrated sulphuric acid in every way as toward similar solutions of ethyl sulphide.

."). A nitrite added to its solutions in couceutrated sulphuric acid gives the same intense green color as with solutions of ethyl sulphide.

6. The organic sulphide thus shown to exist in dog's urine is ethyl sulphide, (CjH5)jS. The mixed sulphide, methyl ethyl sulphide (CHj.CJIs)^, might be thought to have an equal claim with ethyl sulphide as a urinary constituent, since its solutions in concentrated sulphuric acid behave in the same way toward bromine, iodine and nitrous acid, and since the products of its oxidation by the method described are the same, but pure methyl ethyl sulphide that has been several times rectified is easily distinguishable from ethyl sulphide by its odor, which has an additional smell like that of rotten cabbages, not possessed by the latter.'

PURELY CHEMICAL RESULTS.

The points of more especial chemical interest are :

1. The oxidation of ethyl sulphide to acetic and sulj)huric

acids.

3. Its great solubility in concentrated sulphuric acid, and the

ease with which it can again be liberated from this solution

even when dissolved in minute quantities.

3. Its oxidation to a sulphoxide by nitrous acid ;ind its green color reaction with this reagent.

4. Its solubility in water and the ease with which its aqueous solutions can be detected with solutions of iodine in potassium iodide.

5. Also to be noted is the fact that the melting-point of ethyl sulphide mercuric chloride lies at 119° C, and not at 90° C. as stated by Loir and since his time in all- reference books on chemistry.

' See J. Finckh (Ber. d. deutsch. cliem. Gesellsch., 1894, No. 9, p. 1239), wlio finds that these organic sulphides lose their nauseating odor on being repeatedly heated to 290°-300° C. in a sealed tube with powdered copper.

A CASE OF PARANOIA, WITH A STUDY OF THE CEREBRAL CONVOLUTIONS.

By Henry J. Berkley, M. D., Clinical Lecturer in Psychiatry.

Since the pathology of the mental disease known as primary paranoia is entirely unknown, the macroscopic examiiuvtion of the brain in this case nuiy not be devoid of clinical interest. The reader's attention is i)articularly called in the right hemisphere to the region of the post-central furrow, the very broken arrangement of the gyri of the parietal region, the unusual development of the third f rontjil convolution, short, broad, and standing isolated from the other convolutions of the lobe except on its orbital aspect. The external aspect of the left hemisphere is much more in conformity to recognized types, but the inner surface has many points of dissimilarity with the opposite brain-half. Altogether the impression given by

both hemispheres is considerably at variance with the usual types of convolutional development, and the asymmetry between the hemispheres is very marked.

The early history of the patient, Sarah Janet N u, is to

a large extent shrouded in obscurity. Born in Scotland of respectable parents, she was given a fairly good education, and though moderately intelligent, she preferred wandering in the fields with the sheep and heather, to attending school.

She stated that she was always on good terms with her school companions, but at home was restless, all her affections centering in a sister, to the exclusion of the rest of the household. The parents, as well as the brothers and sisters, are

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represented as being healthy, mentally and physically. She also stated that she was married at an early age, and had two children by this husband and another by a lover.

About the age of thirty-five years she emigrated to this country and obtained employment as a housekeeper. She seems to have been fairly successful in giving satisfaction to her employers, though there were several changes during the five years previous to her admission to the City Asylum, and she was discharged from her last situation by reason of her quarrelsome disposition.

In 1890, when she was in her thirty-ninth year, the climacteric began, and by the commencement of July, 1891, all evidence of menstruation had ceased. There were during tlie menopause hemorrhages of some intensity from the uterus, for which she was treated at one of the city hospitals, where she resided several months and until she was obliged to leave. Finally she was sent to the City Almshouse (admitted August 6, 1889), where it was soon recognized that she was insane, being irritable, suspicious, and having marked delusions of persecution, the principal ones being that for a person of her position she was not treated with sufficient respect by the officers of the institution, and that her food was poisoned.

These delusions led to a number of outbreaks of violence against the inmates of the almshouse, and proceeded to the extent of an attack upon the superintendent, and on July 27, 1892, she was transferred to the City Insane Asylum.

At the time of her admission N. was extremely suspicious, and it took the physicians in attendance some time to gain her confidence, and then only by a complete acquiescence with her delusions, the slightest correction annihilating any one in her esteem, and afterwards it was impossible to make her hold any communication.

The jDatient was a tall, angular woman, without any marked signs of somatic degeneration. The skull was sub-brachycephalic, without irregularity in the cranial bones. Physical examination showed the viscera to be healthy with the exception of the lungs, these showing the signs of a beginning tuberculosis at the apices. The heart's action was steady, regular, and without abnormal murmur. There was no history of a traumatism, alcoholism, or of a previous attack of any of the infectious diseases, to supply an etiological factor for the development of the mental trouble.

After the few days necessary to overcome the suspicions she entertained in respect to the medical stafE of the liospit^il, she unburdened herself fully of her troubles and insistent ideas. Delusions of persecution were strongly marked, but by no means paramount. On account of her mission she was molested and persecuted by a multitude of enemies, and though she made a strong effort to preserve outward calmness, occasionally she burst into a torrent of invective upon the heads of her enemies, magnifying the smallest offense against herself into mountains of malice and wickedness.

The delusions of persecution were, however, of small interest in comparison with other fixed ideas, and by contrast sank into the. background. N. believed that she was a prophetess called of God, and was the " woman clothed with the sun, and the moon under her feet, and upon her head a crown of twelve stars," of the XII chap, of the book of the Revelation, and

that her present abode represented the allegorical wilderness where she was to be fed for a space of one thousand three hundred and threescore days, the time representing that of her earthly tribulations, at the end of which period there was to be the judgment day, and without dying she was to be translated to the presence of God. Not only was she to be translated undying, but in some way now unknown to her, and only to be revealed on that great and awful day, she was to take a chief part in the redemption of the human race and intercede between them and the Almighty. At the end of the day of judgment she was to ascend to her prepared abode in the heavenly Jerusalem amidst the rejoicings of the multitude and the "voice of mighty thunderings, saying Alleluia, for the Lord God omnipotent reigneth. Let us be glad and rejoice and give honor to him, for the marriage of the Lamb is come, and his wife has made herself ready" (Eev. xix).

The child spoken of in the first quoted chapter played a very secondary part in her delusion ; she considered the passage to refer to the last of her two male children and the subject played no further part in her history.

The mission on earth was to be a secret one, and while not hesitating to inform those in the immediate circle of her confidence of its purport, she chose not to herald it to the world, preferring to bide the proper time for the revelation.

N. had in her possession a small, well-thumbed Bible, which she carried with her even at meal-times, and coustiintly referred to; in truth, the principal part of her time was spent in delving over its pages, searching for references to herself. Each one when found she marked with a round lead-pencil mark of a definite size. Not only were the passages referring to her marked, but a large number of scattered verses of different import were equally distinguished by a mark, having special reference to some idea or thought.

A few typical passages referring to her may be selected, as (Judges xiii) " Behold thou shalt conceive and bear a son, and now drink no wine nor strong drink, neither eat any unclean thing," a mandate she faithfully endeavored to carry out : or. (I Kings iii) " 1 have given thee a wise and undersbiudiug heart, so that there was none like before thee, neither after thee shall any arise like unto thee," or, "For thy Maker is thine husband, the Lord of hosts is his name, and thv Redeemer the Holy one of Israel, the Lord of the whole earth shall he be called."

The other passages marked in the Hible were exceedinglj numerous. Commencing with a systematic indication in Judges, they increased greatly in .Fob and Psalms, gradually diminished in Isaiah and Jeremiah, and decreased to a small number in the latter books of the Old Testament, In the four Gospels they were comparatively infrequent, increase*! very slightly in the Acts and Epistles, except in Corinthians and Hebrews, where the marks were frequent, and then gradually diminished to Revelation, where only a few chapters were marked, these having especial reference to herself and the New Jerusalem. A rather pathetic notice of the loss of her personal liberty occurred in II Corinthians, where she had m.wked '• where the spirit of the Lord is, there is lil»erty."

The other very nnmerous marked verses may be arrayed under six headings: (1\ Every passage concerning women in

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travail and labor ; (2), all passages referring to the rebuilding of the Temple and descriptions of the New Jerusalem, which she appeared to confound ; (3), numerous references to her troubles: (4), ajjpeals for help; (5), occasional songs of rejoicing ; and lastly, denunciatory passages, which were everywhere indicated and were the most numerous of all, for example, " Behold the day of the Lord conieth, cruel both with wrath and tierce anger to lay the land desolate, and He shall destroy the sinners thereof out of it" (Isaiah xiii).

A considerable number of mouths passed, N. still retaining her delusions perfectly tixed and systematized, without the addition of hallucinations either visual or aural. She refuted all assertions combating any of these ideas by references to various passages in the Bible, and by the argument that all things in that book are from the mouth of God and therefore beyond the possibility of dispute.

Toward the end of the year 1893 the pulmonary tuberculosis began to make rapid advances, persistent diarrhceas set in, accompanied by much abdominal pain that narcotics only partially relieved. Neuralgic pains in the intercostal nerves also added greatly to her sufferings. Nevertheless she clung persistently to life and waited patiently for the day of her translation, not believing in the least that death would result from disease. Albuminuria now shortly developed, and finally death occurred on February 3, 1894.

A summary of the autopsy shows little of interest. All the principal organs with the exception of the lungs were normal. The brain was slightly reduced in volume; the membranes were normal, the gray matter not reduced in thickness to any appreciable extent. The general texture of the cerebral substance was firm.

The Desckiption of the CuREUituM akteii Hahdeninu. a) The Principal Fis^iireit.

The Sylvian fissures conform to the usual arrangement, neither ascending limb penetrating upward more than is ordinarily seen.

The Rolandic sulci of neither side show any unusual variations, though the right reaches a little closer to the interhemispheric fissure than its companion sulcus.

Inter-parietal sulci. — In the right hemisphere the post-central furrow commences in the depths of the Sylvian fissure, and extends to within 3 mm. of the margin of the interhemispheric fissure. It is unbroken by secondary gyri throughout its entire length. The inter-parietal furrow commences 33 mm. above the edge of the Sylvian fissure, and is entirely .separated from the post-central furrow by a tongue of cortical substance extending from the gyri of the superior parietal lobe to the inferior parietal lobe. After running oblicpiely upwards and backwards about 30 mm., the fissure is broken by a broad convolution connecting the upper parietal lobe with the region of the angular gyrus. x\gain commencing behind this gyrus, it immediately throws off a rectangular branch toward the median surface of the brain, the furrow being deeper and longer than is usual, and then following its usual course 30 mm. further, it breaks up into six deep but short radii, and ends, not pene

trating downward into the occipital region after the usual fashion.

The companion sulcus of the opposite hemisphere commences at the margin of the Sylvian fissure, runs obliquely upwards, then horizontally, and descending, penetrates deeply into the occipital lobe. The post-central gyrus of this side offers no anomalies in conformation.

The occipito-parietal sulci of both sides are deep; the left extends 3 mm. further into the lateral surface of the brain than the right, and at its innermost point there is a considerable depression, out of which extend five short branchlets, all having their origin in the fissure. The left fissure extends into the fissure of the hippocampal gyrus, the right runs into the calcariue fissure.

The calcarine fissures and tlie furrow of the corpus callosum follow the usual type.

The formation of the convolutions presents considerable variations from what may be considered the usual development.

b) (■omparison of Ike Conrohitions.

The gyri of the orbital surfaces of the frontal lobes, the convolutions of the island of Keil,the cerebellum and medulla oblongata, present neither asymmetry nor departure from the usual type.

The Frontal Lobes.— Eight Hemisphere.— The superior frontal is very narrow, only 14 mm. in average breadth ; and at its posterior end is almost completely separated from the paracentral lobe by a deep upward extension from the sulcus prtecentralis crossing through the lobe to the median aspect of the hemisphere. At its anterior end it is fused with the substance of the middle frontal gyrus. The surface is furrowed by a few transverse sulci of little depth. The superior frontal sulcus has nothing noteworthy.

Left Hemisphere.— The first frontal of this side is also narrow, averaging 13 mm. The posterior half of the convolution is split into two separate gyri by a horizontal extension forward of a branch of the pra-central sulcus. The upper limb of the convolution joins the convolutions of the prsecentral region, the lower turns obliquely downwards and joins the base of the middle frontal. At its anterior end it is fused with the intricate convolutions of the tip of the lobe. The first frontal sulcus is free from bridging.

Middle Frontal, Left Hemisphere. — This convolution is single, though in its posterior half it is 43 mm. broad, and is conjoined with the anterior central gyrus by a deep-seated pli-de-passage. The gyrus has a large number of short horizontal and transverse sulci of short extent.

Middle Frontal, Kight Hemisphere.— The convolution is much broken by short tertiary fissures, and averages 35 mm. in breadth. At its base a strong bridge is thrown across the pnecentral sulcus, uniting it with the gyrus cent. ant. About midway of its anterior border, a gyrus 6 mm. in breadth crosses the inferior frontal sulcus to the inferior frontal convolution, and divides the sulcus into two unequal portions, the anterior being the longer. The posterior limb of the sulcus turns downward, penetrates completely through the third frontal, and ends far within the fissure of Sylvius.

The Inferior Frontal, Left Side.— This convolution is

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diminutive in comparison with the extraordinarily thick though short fellow of the op2)osite hemisphere. It averages 11 mm. in breadth, and as already described, is united in its middle portion with the second frontal, and at its anterior extremity with the convolutions of the orbital aspect of the lobe, the inf. frontal sulcus extending far forwards, separating it completelv from the convolutions of the second frontal in this region.

The Inferior Frontal, liight ISide. — This convolution is of rounded oval form, averaging 32 mm. in width by 59 mm. in length. It is completely separated from all other convolutions of the lateral surface of the lobe ; in its posterior portion by the praicentral sulcus, and in all other regions by the inferior frontal sulcus, which winds completely around it and descends to the orbital surface of the lobe. This sulcus is confluent at its posterior end with the prajcentral furrow. The convolution is much more complicated than any other of the lobe, the tertiary gyri being numerous. The opercular regions present a uniform view in both lobes.

The sulci prsecentrales presentthe usual bridging extending from the frontal convolutions to the gyrus pri^centralis.

Right Prajcenti'al Gyrus. — This gyrus averages 11 mm. in breadth, and is sjjlit at its base by a deep tertiary fissure extending from the depths of the Sylvian fissure obliquely upward, finally debouching into the prajcentral furrow, thus separating off a portion of the convolution nearly Vi mm. in length. The superior third of the' gyrus is slightly broader than th,e middle portion, and is cut off from the pai-acentral convolution by a deejj transverse incision.

Left Paracentral Gyrus. — This convolution averages 10 nun. in breadth, and is completely broken in its middle third by an unusually deep transverse incision from the sulcus pra^centralis penetrating into the IJolandic fissure just above tlie mentioned bridge from the middle frontal. This deep incision is the only furrow on (he convolution, the remaining portions being smooth.

Right Postcentral Gyrus. — The convolution only averages 8 mm., otherwise there is nothing to note.

Left Postcentral Gyrus. — This fold is exceedingly uneven and rugged; in some portions it is (i mm. wide, in otiiers it is 15 mm.

Right Parietal Lobe. — Besides the unusual development of the gyri crossing the interparietal fissure, the upper lobe is much broken by small vertical sulci, some communicating with the interparietal sulci, others separate from it. In the upper lobe, the gyri supermarginales, while complicated, are not irregular. The angular gyrus is connected with the upper lobe by the above-mentioned inconstant gyrus, otherwise the usual api)earance of the region is retained.

Left Parietal Lobe. — The upper parietal lobe is divided into four gyri running vertically from tlie margin of the interparietal furrow. 'IMie inferior lobe luis no departure from the customary type.

The occipital convolutions on both sides conform to the ordinary arrangement. The intervening sulci are deep.

Right Temporal Region.— The superior convolutions are doubled in their posterior portions by tertiary sulci, and are correspondingly broad. The inferior convolution is narrow in its anterior half, but broadens out considerably where it is confluent with the third occipital gyrus. The fissures present nothing of importance. Tlie occipito-parietal and hippocampal gyri also have no departure from the usual form.

The left temjjoral region is in conformity with the usual type.

Median Aspect of the Right Hemisphere. — The inner aspect of the superior frontal averages 20 mm., in breadth, and is much broken by shallow transverse fissures. !Ncar the paracentral lobe a number of oblique fissures mingle with the transverse. The sulcus calloso-marginalis follows its customary course. The gyrus fornicatus is smooth, except where it merges into the pnecuneus, and averages 10 mm. in width.

The precuneus, cuneus, and the internal aspect of the occipital convolutions have no departure from the common types. The sulcus hippocampi is unbroken by bridges.

Median AsjDect of the Left Hemisphere. — The internal portion of the superior frontal averages 13 mm. in breadth, and is deeply incised by a tertiary furrow at the point where it joins the paracentral lobule.

Passing toward the corpus callosum we immediately come upon a secondary furrow, which, beginning under the knee of the corpus callosum, extends without break to the middle of the inner aspect of the paracentral lobule, ending within the lobule in a forked branch. Beneath- this fissure is a second convolution exactly paralleling the superior frontal, ha^^ng a breadth of 10 mm. It begins in a thin fold confluent with the superior frontal at a point 10 mm. in front of the optic commissure, and extends from tliis point unbroken by any deep incision into the anterior portion of the paracentral lobule, joining it just in front of the sulcus paracentralis by a tongue 3 mm. wide. Beneath this convolution lies the proper sulcus calloso-marginalis, which begins by an incision reaching nearly to the floor of the brain and immediately in front of the optic commissure, and after following the course of the corpus callosum, giving off on the way the sulcus paracentralis, it ends in the usiuil place behind the sulcus centralis. This configuration of the region gives a very broken lobus paracentralis, of less size than ordinary.

The gyrus fornicatns parallels the corpus callosum. is narrow and smooth, and joins with the i)i-a?cuneus after the usual manner.

There is nothing unusual to note in the configuration of the prtvcuueus, cuneus or lingual lobe, except that they are more broken into minor convolutions than in the corresponding regions of the opposite hemisphere.

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[Nos. 44-45.

^:ngio-s^rcom^ ok the ov^^ry.

By Thos. S. Cullen. M. B.

(Reported at the Johns Hopkins Medical Society, Notember 5, 1894.)

L. R, £et. 48. Admitted to the .lohus Hopkins Hospital in the service of Dr. Kelly, July 3, 1894.

Upon entering, the patient complained of enlargement in the lower part of the abdomen, pain in the abdomen and also in the back.

Menstruation commenced at 14 years, has ahvays been regular. She has been married over twenty years, has had two children, the youngest of which is 12 years of age. There is also a history of numerous miscarriages.

Family history unimportant.

History of present illness. — In January the menses became profuse and painful and have continued to be so. During May she first experienced severe grinding pain in the left ovarian region. This has continued and at times radiates down the thighs. Simultaneous with the first appearance of the pain a mass was noticed in the abdomen just above the pubes ; this gradually increased in size.

On physical examination the lower zone of the abdomen is found distended. The superficial veins are congested, and palpation reveals a firm bilobate mass springing from the pelvis. This extends slightly higher on the left than on the right side.

The anterior lip of the cervix is flush with the vaginal wall ; the OS is very patulous, admitting the index finger, and on the left side of the cervical canal a soft mass can be felt. The uterus is enlarged and appears to be continuous with the mass on the left side.

July 7, 1894. Operation by Dr. Kelly. Patient in Trendelenburg position.

An incision 19 cm. long was made in the abdominal wall. On the left side the pelvis was found to be choked by a soft mass ; this was slightly movable, and extending over it was the rectum, which had been displaced toward the right side.

Both the rectum and sigmoid flexure were attached to the tumor by their posterior surfaces. The left ovarian vessels Avere secured and enucleation commenced. In loosening the left side the tumor conmienced to tear, and it was necessary to hurry the operation as much as possible on account of hemorrhage. The uterus was then amputated at the cervix and the cervical stump closed by five silk sutures. Nodules of the growth still remained in Douglas's cul-de-sac, on the left side where the tumor had been separated, and also between the cervical stump and the posterior wall of the bladder.

A large gauze drain was placed in the lower angle of the wound and the abdomen closed by silkworm-gut sutures which included all the abdominal coats. Duration of the operation 51 minutes.

On the following day the drain was removed and about 15 cc. of thick bloody fluid escaped. The discharge gradually assumed the character of pus, and was still present when the patient left the hospital. There was a slight rise of temperature for the first two weeks, 102.5° F. being the highest point reached T'atient discharged .September :i 1.S94.

Pathological report. — That portion of the uterus present is 10x12x9 cm. It is irregularly globular, bright red in color, and covered both anteriorly and posteriorly by a few delicate adhesions. The under cut surface is 5 cm. in diameter. The uterus is firm and non-yielding ; its walls average 2.5 cm. in thickness, and scattered throughout them are numerous homogeneous fatty-like masses, varying from .5 to 1.5 cm. in diameter. One of these presents dark red patches which are apparently small blood-vessels. The posterior part of the fundus is occupied by a submucous nodule 8x7x5 cm. This is somewhat lobulated and resembles raw beef in color. Springing from the lower margin of the nodule and continuous with it is a finger-like mass 6x4x1.5 cm. This projects into the cavity, and its lower teat-like extremity protrudes from thicervix. The uterine cavity is 7 cm. long and approximately 2.5 cm. in diameter. The mucosa on the anterior surface is whitish yellow in color and 1 mm. in thickness.

.Springing from the right side of the cavity is a polyp 1.5 cm. in diameter. The large submucous nodule which projects into the uteriue cavity is not covered by mucosa, but presents a slightly worm-eaten appearance.

The right tube and ovary are of small size and apparently normal.

On the left side of the uterus is a mutilated liiduey-shaped mass 16x10.5 cm., the convexity of which is directed away from the uterus, while the concave portion is adherent over an area 8x9 cm. During operation the tumor was partially divided into three lobulated masses. On separating these still further from one another, they are seen to be composed of fibres which run in parallel rows. These fibres are light red in color and resemble strands of muscle. In the centre of each fibre and running parallel with it is a delicate blood-vessel. Other portions of the tumor are pale, homogeneous and resemble brain tissue, but on further examination are found to be also composed of fibres. There is apparently no breaking down of the tissue. The left tube is 11 cm. long, 5 mm. in diameter. Its outer extremity is adherent to the tumor. The parovarian is intact. No trace of the ovary is to be made out.

Histological examination. — The left ovary is found intimately adherent to the tumor, there being no dividing lintbetween the two. A portion of the ovary is recognized by several large corpora fibrosa and a corpus luteum. The tumor mass is composed of spindle cells cut longitudinally and transversely, these tending to arrange themselves around bloodvessels, which are very numerous.

The vessels have an inner lining of endothelium, surrounding which in some places is a delicate muscular coat, the outer portions of which appear to have undergone hyaline degeneration. Immediately surrounding the muscular coat are 8 to 10 la)'ers of spindle-shaped cells running parallel to the vessel. Such is the condition present where the vascular fibres were seen.

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In other portions of the tumor the blood-vessels are not so abundant, and the spindle cells do not maintain any definite arrangement. Many of the spindle cells have large oval nuclei, others show nuclear figures, while some apparently contain 2 to 3 deeply staining nuclei.

Here and there the tumor shows coagulation necrosis, sometimes with, sometimes without nuclear fragmentation, while in other places polyuuclear leucocytes are present.

The Uterus. — The nodules scattei'ed throughout the uterine wall are composed of cells precisely similar to those of the tumor. There is, however, no tendency toward the arrangement around blood-vessels. The large nodule projecting into the uterine cavity is similar in nature and presents numerous necrotic areas. On its free surface very little degeneration can be made out.

Uterine mucosa. — The cervical glands are for the most part normal ; a few, however, ai'e dilated. The change from the cervical to the uterine mucosa is gradual, the latter being exceedingly thin. The surface epithelium is intact. The glands are scanty in number, cylindrical, and have an intact epithelial lining. Those glands in the depth of the mucosa run parallel to the surface. The stroma of uterine mucosa is of moderate density.

The left tube presents some hemorrhage in the muscular coat, and a few calcareous nodules are seen just beneath the peritoneum. Tiie right tube and ovary also contain a few calcareous nodules.

Z)f«^?iOA'js.— Angio-sarcoma of left ovary. Extension into uterus by continuity and also apparently by metastases, the growth in the uterus being a spindle-celled sarcoma. Atrophy of uterine mucosa, calcareous nodules in both tubes and also in right ovary.

Round and spindle-celled sarcomata of the ovary, although not common, occur with a moderate degree of frequency, and we have been able to gather more than 70 cases from the literature.

Angio-sarconia of this organ is, however, rare, and in most instances has been described under the title " Endothelioma."

Macroscopically the ovary may retain its normal contour, but be greatly enlarged ; sometimes it is lobulated and may be either firm or soft. On section it is often found to contain cyst-like cavities. Some of the tumors appear to be composed of fibres with blood-vessels traversing the centre of each fibre. In these cases a diagnosis can immediately be made.

These tumors have two chief sources of origin : 1st, those arising from the blood-vessels (Aniann (4 cases), Ackermann, Bckardt, Marchand) ; 3d, those springing from the lymphatics (Amann, Flaischlen, Leopold, Marchand, Pomorski, V. Rosthorn, v. Velits and Voigt). These two divisions are again subdivided according as the sarcoma arises from the outer sheath of the vessels or from their endothelial lining,

Otir ease was uniloubfedly perithelial in origin, growing from the outer coats of the blood-vessels. As it is sometimes very difficult, and in fact impossil)lo to say whether it arises from the outer or inner sheath of the vessels, we think the two

divisions are sufficient, viz., those arising from the bloodvessels and those springing from the lymphatics.

These tumors have occurred in children 7 years of age, and in women 64 years old. The average of 11 cases was 33 years.

The chief points in our case were the marked adherence of the tumor to the surrounding structures, the typical vascnlar fibres enabling us at once to diagnose it as angio-sarcoma, and the metastases in the uterus.

Dr. Welch. — I have jjut under the microscope a specimen of an angio-sarcoma which is parallel to that of Dr. Cullen's. It is a most typical example of angio-sarcoma. A large tumor had grown in the axillary region, developing from the axillary lymphatic glands. It was operated upon by Dr. Keyes in New York. The operation was of unusual difficulty on account of the severe and almost uncontrollable hemorrhage. After the operation the tumor rapidly returned and there were metastases widely distributed in many organs of the body.

Dr. Cullen described his tumor as looking like a mass of muscle fibres. In my case it looked more like a mass of nerve fibres running parallel to each other, each fibre presenting a small central lumen. The tumor consists of blood-vessels running parallel with each other, and the tumor cells form the covering to the blood-vessels. There is an endothelial wall, then a few strands of circular muscle, then a little hyaline material, and then the tiimor cells proper. The tissue between these strands is made up to a large extent of extravasation of blood, a few cells and a few strands of connective tissue.

Amann : Arcliiv f. Gyn., lS<t4, Bd. XLVI, S. 4S4.

Eckardt : Zeitschr. f. Geb. u. Gyn., 1SS9, XVI, S. 344.

Flaischlen : Zeitschr. f. Geb. u. Gyn., Bd. VII, S. 449.

Leopold : Arehiv f. Gyn., 1873-74, Bd. VI, S. 202.

Marchand : Beitrage zur Kenntniss der Ovarien-Tumoren, Halle, 1879, S. 50.

Pomorski: Endothelioma Ovarii. Zeitschr. f. Geb. n. Gyn., 1890, XVIII, S. 92.

v. Rosthorn: .Archivf. Gyn., 1891, XLI, S. 328.

V. Velits : Zeitschr. f. Geb. u. Gyn., 1890, XVIII, S. 106.

Voigt : Z'lr Kenntniss des Endothelioma Ovarii. Arcliiv f. Gyn., 1894, XLVII, S. 560.

Description of Pl.vte. f natural size.

The specimen is viewed from behind, the uterus being cut open. On the left side a large, somewhat lobulated and torn mass is se«n ; attached to the outer margins of this are a good many adhesions. The lower and inner portion of the tumor is composetl almost exclusively of fibres running parallel to one another. The mass is intimately adherent to theleft side of the uterus.

The uterus is at least three time.'* its normal siie, its walls being twice their usual thickness, while studding the uterine niascle are irregularly lobulated or round nodules. These are of a yellowish waxy appearance and stand out prominently. The uterine cavity is occupied by a large submucous nodule, attached to the lower surface of which is a ragged mivss that projects into the cervix. The lower portion of the uterine cavity and 'a small part of the cervical cjinal are visible.

To the right of the uterus portions of the right tul>e and ovary can be distinguished.

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JOHNS HOPKINS HOSPITAL BULLETIN.

[N08. 44-45.

PROCEEDINGS OF SOCIETIES.

THE JOILNS HOPKLXS HOSPITAL MEDICAL SOCIETY.

Meeting of November 5, 1894.

Dr. Kelly in the Chair.

NOTES ON XKW BOOKS.

BOOKS RECEIVED.