Talk:The Johns Hopkins Medical Journal 8 (1897)

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POSTURAL METHOD OF DRAINmG THE PERITONEAL CAVITY AFTER ABDOMINAL OPERATIONS.

By J. G. Clark, M. D.


The general trend of recent medical literature relating to iutraperitoueal drainage tliroiigh the abdominal incision has been towards the limitation or reduction of the number of conditions demanding its employment, and a few European gynecologists have even gone so far as to discard drainage entirely, leaving the peritoneum to protect itself.

In a forthcoming article* on drainage based upon the bacteriological study of a large number of cases and upon the clinical records of 1700 cases of abdominal section performed in the gynecological department of the Johns Hopkins Hospital, I have been forced, notwithstanding my preconceived ideas in favor of drainage, to draw conclusions against it and to coincide with those few writers who discard it altogether.

The benefits to be derived from any form of drainage when used for the purpose of removing infectious matter from the peritoneal cavity, are infinitesimal compared with the untoward or disastrous results which may follow its use.

The greatest safety lies in closing the abdomen without drainage, except in cases of purulent peritonitis or in operations when there has been extensive suturing of the intestines, and in a few other rare conditions which I shall consider in detail in my paper on drainage.

Escape of pus during an operation, oozing of blood or serum, extensile raw areas in the pelvis, are usually sui:)posed toindi


  • A Critical Review of 1700 Cases of Abdominal Section from the

Standpoint of Intraperitoneal Drainage. The Johns Hopkins Hospital Reports, Vol. VII.


cate the necessity of some form of drain ; on the contrary, these are the cases which should be left to the care of the peritoneum, as demonstrated by a comparative study in our series of 1700 cases of abdominal section of a hundred cases each of similar pelvic inflammatory affections, drained and undrained. The undrained cases presented by far the best results.

Every surgeon recognizes the dangers of dead spaces in the abdominal cavity and endeavors to prevent their formation, but frequently this is impossible. Mikulicz first called attention to this subject in a forcible paper, and devised a siJecial drain for the prevention of oozing and for the removal of fluids from dead spaces; but this method, like all others, is unsatisfactory because the principle upon which it is based is wrong.

In an article (1889) by Laude the statement is made that it is not the principle but the methods of drainage which are wrong. I would reverse this statement by saying that it is not the method but the principle which is wrong. Zweifel claims that the subject of drainage should no longer be considered in surgical treatises, but should be relegated to medical history.

The chief objections to drainage of dependent pockets in the pelvis or abdomen through an abdominal opening are, first, fluids are frequently not removed, but on the contrary are pent up by the gauze drain ; and second, instead of removing infection, the gauze or tube may be the means of introducing it from the outside into the degenerated fluids.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 73.


To overcome the dangers of dependent pockets and dead spaces in the pelvis, I would suggest the elevation of the patient's body after operation to a sufficient height to start the flow of collecting fluids from the pelvis towards the diaphragm, and thus promote the rapid elimination by the normal channels of exit from the peritoneal cavity, of infectious matter and of vital fluids which may stagnate in these pockets and form a culture medium for pyogenic micro-organisms.

Although it would appear at first sight that this method of drainage is opposed to sound surgical principles, I hope to offer proof from a review of recent literature bearing upon the function of the peritoneum under normal and pathological conditions, sustained by the clinical report of three cases, that it is not only a safe but may be a life-saving measure.

Function of the Peritoneum under Normal and Pathological Conditions.

G. Wegner,* the first investigator who by experiments upon animals endeavored to arrive at some definite conclusion concerning the ability of the peritoneum to rid itself of injurious fluids or solid particles, was convinced that a comparatively large quantity of infectious matter could be eliminated or encapsulated by the peritoneal exudate without serious harm to the animal.

Grawitzf next took up the experimental study of infection of the peritoneum, pursuing his investigations under improved bacteriological technique, and arrived at the following conclusions :

1. The introduction of non-pyogenic organisms into the abdominal cavity, either in small or large quantity, or mixed with formed particles,J produces no harm.

2. Great quantities of organisms which ordinarily produce no symptoms, may give rise to a general sepsis if the absorptive function of the peritoneum is impaired.

3. Injection of pyogenic organisms into the peritoneal cavity may be quite as harmless as injections of non-pathogenic varieties. (In these experiments he injected a flocculent emulsion of staphylococcus albus and aureus and the streptococcus pyogenes in ten cubic centimeters of water without any visible reaction.)

4. The introduction of pus-producing cocci into the normal peritoneal cavity produces a purulent peritonitis, first, if the culture fluid is difficult of absorption, and second, if irritating materials are present which destroy the tissues of the peritoneum, thus preparing a place for the lodgment of the organisms, and the production, of an exudate upon which they may grow.

Pawlowsky,§ in an excellent experimental study, reviewed Wegner's and Grawitz's work, with whom he agreed in many


  • Chirurgische Beobacbtungen uber die Peritonealhole mit besonderer Beriicksichtigung der Ovariotomie. Verhandlung der deutschen Gesellschaft fiir Chirurgie, Berlin, 1877.

tCharite Annalen Jahrg., XI, 1886.

t A solution of fecal matter containing solid particles was injected ; the fluid was absorbed while the larger particles were encapsulated.

§Virchow's Archiv, No. 117, p. 469, 1889.


particulars, but disagreed in others. The main point of difEerence, however, between Pawlowsky and Grawitz related to the ability of the normal peritoneum to deal with the staphylococcus aureus.

Pawlowsky found that the large quantities of staphylococci injected by Grawitz without harm into dogs produced death very rapidly in the animals upon which he experimented, and that only a minimum quantity was harmless.

Reichel* went over the same ground in an experimental research, and in the main agreed with Grawitz. The essential points of value in Reichel's paper are, that peritonitis usually arises, first, because more organisms gain entrance than can be handled by the peritoneum, and second, because the stagnation of degenerating fluids in dead spaces favors the growth of the organisms.

He also accounts for Grawitz's and Pawlowsky's conflicting results, on the ground that some animals are more susceptible to infection than others, and that there are marked differences in the virulence of cultures of the same organism under varying conditions.

A carefully conducted experimental research by Waterhouse,t carried out under the oversight of Orth, appears to me to satisfactorily settle the question of the ability of the normal peritoneum to take care of infection.

He injected 6 cc. of a cloudy culture of staphylococcus aureus into the abdominal cavity of dogs, employing both the methods of Grawitz and Pawlowsky, and all of the animals survived. The same results were obtained with the streptococcus, bacillus pyocyaneus and the intestinal bacteria.

Waterhouse then endeavored to simulate the conditions occasionally met with after operations, by introducing 8 cc. of urine and small quantities of blood with the cultures, and again the results were negative. If, however, 15 to 20 cc. of fresh blood were introduced into the peritoneal cavity, followed in a few minutes by the staphylococcus aureus, severe peritonitis was produced.

In these experiments Waterhouse agreed with Pawlowsky and Grawitz that the dangers of peritonitis are increased by tardy absorption of fluids, which in effect leaves a culture medium for the growth of the organisms.

After the introduction of blood clots 3 cm. in size, followed by the staphylococcus aureus, death occurred from peritonitis in 24 hours.

Waterhouse also found that the purulent exudate from acute abscesses is extremely virulent, 2 cc. of the staphylococcus aureus and 1 cc. of the streptococcus from this source causing death in twenty-four hours. If a very small quantity of the pus, however, was introduced with water, the animals frequently survived.

After the introduction of turpentine with the organisms, as done in Grawitz's experiments, peritonitis did not follow, which is explained by Waterhouse on the ground that the organisms are rendered inactive or are killed by the turpentine. He proved this point by injecting the turpentine first


  • Beitrage zur Aetiologie u. chirurg. Therapie der Sup. Peritonitis. Deutsche Zeit. f. Chir., Vol. XXX, 1889.

t Virchow's Archiv, Vol. 119, p. 342, 1890.


April, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


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and following it in a short time with the infecting germs ; in every instance the animal died of peritonitis.

Dogs with a strangulation of the intestines were easily infected.

In three instances the staphylococcus aureus was introduced into the peritoneal cavity of cats suffering from ascites, followed quickly by death from peritonitis, which resulted, as Waterhouse says, because there was a favorable culture material, a diminished absorption, and an injury to the peritoneal endothelium.

Burginsky* in a series of experiments also came to the conclusion that the discrepancies in the results of Pawlowsky's and Grawitz's experiments were due to variations in the virulence of the cultures employed.

Halstedf confirmed and extended the views of previous observers concerning the resistance of the normal peritoneum to infection, and called attention to the dangers of introducing pyogenic organisms about a ligated or strangulated area, or in conjunction with insoluble bodies. Pieces of sterile potato introduced into the peritoneal cavity of control animals were soon encapsulated and produced no disturbance, but when infected with pyogenic cocci, invariably caused peritonitis.

A recent paper by Cobbett and Melsome,J on " Local and General Immunity," contains some valuable observations bearing upon the resistance of the peritoneum to infection.

Notwithstanding the injection of large quantities of virulent streptococci, a few of their animals survived. They state that " in those animals which succumbed quickest, free cocci were very numerous in the peritoneal exudation, and in those which survived longest they were either absent or contained within phagocytes."

These observers, in order to discover how quickly the organisms disappeared from the peritoneal cavity, killed two rabbits which appeared about to recover. " In the first, which had received 5 cc. of broth culture thirty hours before, only one chain of streptococci was found after prolonged search, but many cocci were contained in cells, and broth inoculated with this fluid grew a good culture."

"The second rabbit having shown no signs of illness after an injection of 6 cc. of anaerobic broth culture, received next day 10 cc. of a similar material swarming with streptococci. When killed five and a half hours later, not only could no streptococci be seen, either free or in cells, but no growth grew on cultures made from the abdominal fluid."

From this review of the literature bearing upon infection of the peritoneum I make the following summary :

1. Under normal conditions the peritoneum can dispose of large numbers of pyogenic organisms without producing peritonitis.

2. The less the absorption from the peritoneal cavity the greater the danger of infection.

3. Solid sterile particles, such as fecal matter, potato, etc., are partly absorbed and the remainder are encapsulated without the production of peritonitis.


•Baumgarten's Jahresbericht, Vol. VII, 1891.

tThe Johns Hopkins Hospital Reports, Vol. II, 1891.

t Journal of Pathology and Bacteriology, 1895.


4. Death may be produced by general septicaemia, and not by peritonitis, where large quantities of organisms are taken up by the lymph streams.

5. Irritant chemical substances destroy the tissues of the peritoneum and prepare a place for the lodgment of organisms which becomes the starting-point for peritonitis.

6. Stagnation of fluids in dead spaces favors the production of peritonitis by furnishing a suitable culture medium for the growth of bacteria.

7. The association of infectious bacteria with blood clots in the peritoneal cavity is especially liable to produce peritonitis.

8. Traumatic injury or strangulation of large areas of tissue are strong etiological factors in the production of peritonitis when associated with infectious matter.

The accumulated evidence of all these investigators proves beyond question that the peritoneum, under normal conditions or even when greatly handicapped by disease or artificial conditions, is capable of overcoming the invasion of comparatively large quantities of pyogenic bacteria.

Mechanism of Absorption of Fluids and Solid Particles in the Peritoneal Cavity.

Recent investigations by Muscatello* on the histology of the diaphragmatic peritoneum and the mechanism of absorption of substances from the peritoneal cavity, when considered in conjunction with the above conclusions, give ample ground for my suggestion of the elevated posture as a prophylactic measure against post-operative peritonitis.

Muscatello accepts Bizzozero's and G. Salvioli's classification of the component parts of the diaphragmatic peritoneum which occur in the following order: endothelium, membrana limitans and connective tissue framework. Up to the time of Muscatello's publication, histologists were equally divided on the question of the presence or absence of stomata between the endothelium. He proved beyond doubt that these openings are optical illusions, due to the defective preparation and staining of the microscopical sections. According to Muscatello's opinion, minute foreign particles, leucocytes and fluids pass through openings between the endothelium of the diaphragm made by the retraction of the protoplasm of the cells.

Beneath the peritoneal endothelium of the diaphragm and between the connective tissue fibres are open spaces 4 to 16 mm. in diameter, occurring in groups of 50 to 60, which communicate with the lymph vessels. A careful search for these spaces failed to reveal them in any other portion of the peritoneum.

G. Wegner first proved that the peritoneum was capable of absorbing the most remarkable quantities of fluids, equivalent to three to eight per cent of the bodily weight in one hour, or the animal's entire weight in twenty-four hours.

By the injection of foreign particles suspended in a fluid medium into the peritoneal cavities of dogs, Muscatello was able to demonstrate the existence of an intraperitoneal current which carried fluids and small particles towards the diaphragm, regardless of the animal's posture. The rate of transmission


Virchow'a Archiv, 1895.


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[No. 73.


of the foreign particles from the peritoneal cavity to their ultimate repository, the lymph glands, could, however, be increased or retarded by the influence of gravity.

In those dogs which were suspended with head down, carmine bodies appeared in the retrosternal and thoracic lymph glands in from five to seven minutes, while in animals in which the posture was reversed it was five and a half hours before they could be recovered from these glands.

Muscatello proved that small particles were carried from the peritoneal cavity into the lymph spaces of the diajihragm through the opening made by the retraction of the endothelium, then into the mediastinal lymphatic vessels and glands, then into the blood current, by which they were transported to the various organs of the body, from which they were picked up by the lymph vessels and deposited in the collecting glands of each organ. For this reason the large vascular organs, such as the liver, stomach, spleen and pancreas, show the particles first and in the greatest numbers, while the lymph glands of the mesentery, which gather their vessels from a limited area of the intestine, contain but few of the granules.

The function of the leucocyte is of especial importance in the elimination of foreign particles from the peritoneal cavity.

Muscatello and other observers find, on examining the precipitate in the peritoneal cavity after injecting innocuous foreign particles or bacteria, wandering cells interspersed among the particles, some of which are lightly laden with granules, while others are apparently distended to the point of bursting, and still others which have not yet taken up their burdens.

In some instances where the granules are too large for one leucocyte to encompass it, two or more join forces to surround the invader. The leucocytes are found in greatest abundance beneath the omentum. Prom the peritoneal cavity Muscatello traces the course of the leucocyte through the channels above described and finally finds them deposited in the lymph glands in various parts of the body.

In Muscatello's experiments the leucocytes were able to dispose of the innocuous particles rapidly and without apparent ill effect to the auimals. In Pawlowsky's, Cobbett's and Melsome's experiments, on the other hand, the conditions were different, the leucocyte having to meet an antagonistic invader. In those animals which survived the injection the infectious organisms were quickly encompassed by the leucocytes and carried into the general circulation, while in the fatal cases the peritoneal exudate was found swarming with free organisms and only a comparatively few enclosed in leucocytes.

The points in Wegner's and Muscatello's articles which I wish to draw especial attention to are :

1. Large quantities of fluids may be absorbed by the peritoneum in a remarkably short time. (Wegner.)

3. Minute foreign particles are carried from the peritoneal cavity through the diaphragm into the mediastinal lymph vessels and glands, and thence into the blood, by which they are transmitted to the organs of the body, especially those of the abdomen, and later appear in the collecting lymph glands of these organs. (Muscatello.)


3. The leucocytes are largely the bearers of foreign particles from the peritoneal cavity. (Muscatello.)

4. There is normally a current in the peritoneal cavity which carries fluids and foreign particles towards the diaphragm, regardless of the posture of the animal, although gravity can greatly favor or retard it. (Muscatello.)

Postural Method of Draining Dead Spaces in the Pelvis.

The many bacteriological studies in cases of experimental and post-operative peritonitis and in experimental infections of the peritoneum show conclusively that the infecting organisms are quickly distributed more or less generally in the peritoneal cavity, from whence they are carried into the system at large.

Where there is no persistent source of infection, virulent species of bacteria may be destroyed effectually in this way; but when a nidus of infection exists in which the microorganisms are propagated, the patient is either carried off by a rapidly fatal septicaemia or peritonitis, or the peritoneal exudate forms a barrier to the further distribution of the infectious matter, which then follows the clinical course of any localized collection of pus.

To avoid this danger the most scrupulous care should be observed in every abdominal operation not to leave behind any condition which may furnish a starting point for an infectious process.

Oozing should be controlled as far as possible, injury and exposure of the peritoneum should be guarded against, raw areas should be covered with adjacent healthy peritoneum when practicable, and all debris and fluids should be removed as far as possible before the abdomen is closed.

Notwithstanding every precaution, dead spaces will be left after many operations, which may become collecting places for degenerating fluids. In addition to these artiflcial spaces, oozing serum and blood may collect in Douglas' cul-de-sac or in the ante-uterine space, and become the focus of a genei'al peritonitis or a localized pelvic abscess.

To offset these dangers all dependent spaces should be drained as rapidly as possible, thus preventing the collection and stagnation of vital fluids, which are active germicides when first secreted, but become excellent culture media when degenerated.

By elevating the pelvis after operation, the normal intraperitoneal current may be assisted greatly in at once draining dead spaces, and thus give the general peritoneal cavity and system at large the best opportunity to meet the invading organisms before they have had time to increase in numbers. To remind one of the incredible rate of multiplication of micro-organisms it is only necessary to quote Cohn's classical statement that "one germ under proper conditions may give rise to more than a half million of similar organisms within twenty-four hours."

Stagnating fluids in the dependent parts of the abdominal cavity or in dead spaces may furnish such a favorable culture bed that a few organisms may quickly generate myriads of others and overcome the most resistant germicidal forces ; if on the other hand these spaces can be prevented from filling with fluids the organisms may easily be overcome.


April, 1897.]


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In additiou to tbe mere transportation of the organisms from an area of decreased resistance to one of normal resistance, the irritant chemical toxines elaborated by the bacteria are diluted and the infectious matter is divided into a fine granular state, thus giving the leucocytes the best opportunity to encompass the organisms.

Although fatal septicasmia may be produced in animals by the absorption of large quantities of organisms from the peritoneal cavity, it appears to me correct to assume that after a well-conducted abdominal operation no such quantities of organisms will be left behind as are necessary to jiroduce septicemia in the animal experimentally. If such a condition should exist the patient would certainly die from the rapid multiplication of the organisms in dependent cavities. Hence I conclude that the better chance for the patient's recovery lies in the direction I have indicated.

My arguments therefore in support of this postural method of drainage are, first, stagnating fluids are prevented from collecting in dead spaces in the pelvis; second, infectious organisms are quickly carried into normal areas of the body where they are destroyed before they can increase in numbers; and third, toxic substances elaborated by the organisms are diluted and prevented from expending their irritant effects on a wounded area.

The method which I desire to offer is briefly as follows: At the conclusion of an operation all fluids and debris should be removed as far as possible by sponges, after which the abdominal cavity should be thoroughly irrigated with normal salt solution until the fluid comes away clear.

When the irrigation fluid is all sponged out, 500 to 1000 cc. of salt solution should be poured into the peritoneal cavity, so that when the patient is elevated after she is returned to the ward the artificial current may be started at once towards the diaphragm, thus supplementing the normal current.

After the introduation of the salt solution the omentum and intestines should be replaced in an orderly way and the abdomen closed.

As soon as the patient is returned to her room, the foot of the bed should be elevated about 30 degrees, which gives sufficient inclination of the posterior pelvic wall to assist the flow towards the general peritoneal cavity. This posture should be maintained for twenty-four to thirty-six hours, after which the bed may be lowered.

Leaving the salt solution in the abdominal cavity is not a novel procedure, as it has been done in a large number of cases during the last two years in the gynecological department, and other abdominal surgeons have used it with good effect.

This postural method of drainage is offered as a prophylactic measure against post-operative peritonitis, but not as a curative measure after the peritonitis is established.

It should therefore not be employed when an operation is performed for the relief of purulent peritonitis or for inflammatory conditions associated with general peritonitis, as for instance some cases of appendicitis.

From the experiments of Waterhouse in which he proved the danger of infection in cats suffering with ascites on account of the defective absorptive mechanism, it would also appear unsafe to adopt the postural method in cases when


this complication is coincident with the surgical affection. Pawlovvsky has sliown in his excellent experimental investigations that the lymph channels leading from the peritoneal cavity are choked with the infectious bacteria and inflammatory products in purulent peritonitis, and therefore advises free drainage through an abdominal incision.

In these cases it is evident that the multiplication and virulence of the organism have been too great for the phagocytes to overcome successfully, and that the only method of treating this condition is to remove as much pus as possible by irrigation with salt solution or by mopping the peritoneal surfaces with sponges wet with salt solution, as suggested by Finney, and then to insert a very free drain.

Only one of the cases which I report in this paper showed organisms on culture. The presence of pyogenic organisms is not a contraindication to the employment of the jiostural method, because all investigations have proved conclusively that the peritoneum can overcome the invasion of large numbers of the most virulent organisms. Cases of pelvic inflammatory diseases, howevei-, rarely come to operation while the organisms are yet active, as shown by Miller of the Johns Hopkins Hospital, Schauta, Menge and others.

In forty-four cases of hysterectomy, mostly for pelvic inflammatory disease, examined by Miller, the cultures made from the interior of the uterus were negative, and cultures from the pus obtained from 51 cases of pyosalpinx, ovarian abscess and pelvic abscess, were negative in all but one case which showed gonococci.

Report of Cases in which the Postural Method of Drainage was employed.

Case I.

In this case all of the conditions usually supposed to indicate imperatively the emjiloynient of some one of the established methods of abdominal drainage were present.

Among these the chief indications were a sejitic temperature with great prostration of the patient before operation, and during the operation the separation of wide-spread adhesions which produced extensive injury to the peritoneum and free oozing of blood, the escape of a large quantity of pus and degenerated blood clots into the abdominal cavity. In addition to these conditions portions of the cyst wall and degenerated matter, and, most dangerous of all, a large cupshaped dead space beneath the intestines and mesentery, were left at the close of the operation.

Gynecological No. 4946. E. B. L., admitted January 18, 1897. Married, age 47 years.

Complaint. Pain in the lower abdomen, more marked on the right side. Slight cough.

Marital History. Married 16 years ; one child 16 years old; labor easy, puerperium normal, no miscarriage.

Menstruation. Began at 13 years, regular, normal. Last period terminated December 18, 1896.

Present Illness. November 15, 1896, she had a severe chill, lasting two hours, followed by fever. The next day she had great pain, which continued one week and was accompanied with diarrlia.'a. Since then she has grown steadily weaker.


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[No. 73.


fever and chills occurring frequently, and for the last week she has been confined to bed.

General Condition. Well nourished woman; tongue slightly coated, bowels regular, appetite poor. Micturition and defecation painless. For the past four weeks she has had a dry cough.

Examination of heart and lungs negative.

Temperature on admission 103° F., pulse 110.

Diagnosis. Large suppurating ovarian cyst.

Operation by Dr. Kelly, January 20, 1897. Cystectomy; part of cyst wall could not be removed.

Complications. Extensive adhesions to mesentery, bowel and vermiform appendix. Adhesions to entire posterior pelvis, to omentum, to bladder, and to anterior abdominal wall. Patient greatly prostrated, pulse before operation 118, at close 144, during operation as high as 156.


Incision 14 cm. in length, exposing red mottled and whitish cyst wall, closely adherent to anterior abdominal wall over a surface 10 cm. above symphysis pubis. Omentum adherent to anterior face of cyst over an area 10x8 cm. Adhesions separated; free oozing from thickened omentum checked by catgut sutures, no omentum removed; just above this point there was a fringe of flat adhesions, binding cyst to intestines and skirting the whole upper border of tumor from left to right. Adhesions so dense that separation was impossible without great injury to intestines.

Tumor tapped, about 3000 cc. of thick, fetid, yellow pus evacuated; the puncture was then closed with sutures.

Ten minutes were spent in separating tumor from anterior abdominal wall, bladder and anterior pelvic wall.

Large Fallopian tube on left side was exposed up to a point


Jan.


18


19 20


21


23


24


25


26


Temp.

103 102 101 100

99

98

Temp.

Pulse Resp.

Stools


Day of Operation


6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 12 6 le 6 12 6 l2 P^l'se



5(10


540


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670


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190 +


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130 120 110 100 90


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Case I. Plain line indicates temperature. Broken line indicates pulse.


where it was lost in the tumor. Adhesions to uterus, to pelvic floor on right side, and to part of left pelvic wall divided. On floor of pelvis a sac coutaining 300 cc. of thick brown pasty blood was evacuated. Ovarian vessels at left pelvic brim exposed by dissecting with knife, fingers and scissors, and ligated, the left cornu uteri was then tied off and cyst cut loose from top of left broad ligament.

In separating adhesions on pelvic floor a sac was ruptured, discharging a large quantity of fetid pus into the peritoneal cavity. This was quickly mopped out and the hole in the sac stuffed with gauze. Cyst cut loose, leaving a portion of abscess wall 5x8 cm. in dimensions on the pelvic floor. Gauze


packed over this to protect it during the rest of the operation. Sac was peeled up and out of a dense bed of adhesions in the pelvis ; it was then found that the adhesions, extending between the entire length of the mesentery and out onto the intestines, were too extensive for further separation. The outer layers of the cyst wall were slit 2 cm. from bowel on all sides and dissected out from beneath the mesentery, thus completing the enucleation and leaving behind a large cup-shaped dead space. Slight capillary oozing occurred from the portion of cyst wall remaining behind.

The portion left in the pelvis also required six or eight ligatures to control oozing. Small epithelial cyst on right side


April, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


65


piiuctured. Eight ovary normal. Eight tube adherent and closed.

Adhesions of right ovary to sac bled freely, requiring two sutures to control hemorrhage.

At completion of operation the abdomen was freely irrigated with many litres of salt solution, after which 700 cc. of salt solution were left in the abdomen. Abdomen closed with buried silkworm gut and subcutaneous catgut sutures.

Day of Operation. Patient's cough very troublesome, pulse 116, temperature 101° F. before operation. Eeturned from operating, room at eleven o'clock, pulse 140, respiration -18, profuse perspiration over entire body. Twelve o'clock, pulse 132, respiration 46. One o'clock, pulse 129, respiration 44. Two o'clock, foot of bed elevated twenty inches. Five o'clock, pulse 116. Six o'clock, pulse 116, temperature 100.4° F. Twelve o'clock, temperature 100.3° F., pulse 128. Patient uncomfortable, but not suffering great pain.

Second Day. Six o'clock A. M., temperature 99.6° F., pulse 126. Patient slept in all about two hours, often rendered uncomfortable by cough and heavy perspiration. Bed lowered.

Twelve o'clock noon, temperature 98.8° F., pulse 126. Patient has been comfortable up to this time, cough more troublesome, she now feels nauseated. Six o'clock, patient has vomited four times during afternoon, but is now comfortable, temperature 99.4° F., pulse 120.

Twelve o'clock midnight, temperature 99.3° F., pulse 124. Cough troublesome.

Third Day. Patient slept most of the night, awakened at intervals by paroxysms of coughing. Bowels moved. Temperature 98.8° F., pulse 124.

Twelve o'clock noon, temjDerature 98.6° F., pulse 114. Six o'clock, temperature 98.8°, pulse 108. With exception of pain produced by coughing, patient has passed a comfortable day.

Twelve o'clock midnight, temperature 100.4° F., pulse 118.

Fourth Day. Six o'clock, temperature 99.6° F., pulse 118. Bowels well moved, patient comfortable. Twelve o'clock noon, temperature 99.4° F., pulse 116, patient very comfortable. Six o'clock, temperature 99° F., pulse 110.

From the fourth until the tenth day the patient made as perfect a recovery as the most uncomplicated cases of abdominal section. The abdominal dressings were removed on the tenth day; incision healed /;er primam, subcutaneous suture entirely absorbed. Cough ceased about this time. Patient sat up in bed on the sixteenth day, and was out of bed in a wheel chair on her nineteenth day, and was able to walk on her twenty-fifth day. She was discharged from the hospital on her thirty-fifth day, feeling perfectly well.

Case II.

In this case the operation was very difficult and attended by many complications. The peritoneum was injured extensively, pus escaped during the operation, the intestine was injured and required suture, free oozing occurred during the operation and persisted at its completion, and large denuded areas were left in the pelvis.

Gynecological No. 4892. A. E. T., widow, aged 34 years.

Complaint. Pain in the right inguinal region, pain in the rectum, and swelling of the abdomen at times.


Menstruation began at fourteen, flov scanty but regular, lasting two to three days; always painful before marriage, since then painless.

Marital History. Married 14 years ago ; husband has been dead eight years. Four children, oldest 14 years, youngest 8 years of age. First labor instrumental, the others were easy. No miscarriages.

Family History. Negative.

Present Complai?it. Three years ago she was confined to bed for three weeks with fever and chills and severe pain in the lower abdomen, which began in the right side and then shifted to the left. During the attack she had a constant discharge of thick tarry blood from the uterus. After the attack she was able to get up, but it soon recurred, and the abdomen became greatly distended and excessively painful. Ten days ago another attack began, which has not been so severe up to this time as the former ones. She complains of pain during defecation and micturition, backache and bearingdown pains. Temperature on admission 101° F., pulse 120.

Diagnosis. Pyosalpinx duplex ; retroflexio uteri adherens; pelvi-peritonitis.

Operation. Enucleation of both ovaries and tubes.

Complications. Dense adhesions binding pus sacs to pelvic walls and rectum, close relation of abscess on right side with the iliac vessels, persistent oozing following operation, escape of pus during the operation into the abdominal cavity.

Incision 12 cm. through thin abdominal walls, intestines packed back into abdomen with gauze bolsters. Impossible to differentiate pelvic structures at first on account of the dense adhesions covering in and binding all of the organs together.

Sigmoid flexure released from mass to which it was bound by dense adhesions. Outer coat of the bowel torn for about 3 cm. during the separation, but was at once closed with interrupted catgut sutures.

The enucleation was then begun on the floor of the pelvis, working upward and freeing the ovary and tube which formed a sac containing 30 cc. of pus. These structures were then tied off and cut away from the pelvic wall.

The fundus of the uterus was then partially liberated from adhesions, but this was discontinued on account of the free bleeding and danger of tearing into the rectum.

A long fusiform mass on the right side extended along the iliac vessels, with which it was closely adherent, around in front of the bladder. The sac contained 60 cc. of thick white pus, which partly escaped during the operation.

After freeing all the adhesions, the round ligament and ovarian vessels were tied off and the mass excised.

Active oozing to the right of the fundus over the ureteral area, also posterior to the fundus. After controlling several of these points there was still free hemorrhage at a point on the pelvic floor to the left of the rectum and from another point on the under surface of the broad ligament. This oozing was sufficient to stain a sponge as fast as it could be applied. The abdomen was irrigated thoroughly with salt solution, after which the bladder and fundus and the fundus and parietal peritoneum were stitched together to control oozing and to cover the raw areas with peritoneum.


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[No. 7.3.


500 cc. of salt solution left in abdomen. Pulse at beginning of operation 93, at end 150. Time of operation one hour and a half.

First Day. Patient returned to ward at four P. M., pulse 140. Bed elevated. Four thirty P. M., pulse 120, of good volume; six o'clock, pulse 104; seven o'clock, 100; nine o'clock, 96; twelve o'clock midnight, 88. Patient recovered quickly from ether without symptoms of shock.

Second Day. Six o'clock A. M., temperature 100° F., pulse 9G. Patient complains of much pain. Twelve o'clock, pulse 92, temperature 100.8° F., patient sleeping quietly. Six o'clock P. M., temperature 100° F., pulse 100. Twelve o'clock midnight, temperature 99.8° F., pulse 92. Patient sleeping quietly.


Tliird Day. Six o'clock A. M., pulse 84, temperature 99.3° F. Bowels slightly moved. Condition remained about the same during day. Patient complained of some nausea, but did not vomit.

Fourth Day. Six o'clock A. M., pulse 80, temperature 99.4° F. Patient rested well, still slightly nauseated.

Fifth Day. Six o'clock A. M., temperature 99.6°, pulse 72. Bowels effectually moved, well formed stool. Patient passed a very comfortable day. From this time on the patient made a good recovery. On the tenth day after her operation the temperature rose to 100° F., and continued about this point until her seventeenth day, when it dropped to normal. At the time of her discharge she was feeling well.



V)a.y a?

Operation


Case II. Plain line indicates temperaiure. Broken line indicates pulse.


Case III. In this case there were dense adhesions binding a large suppurating ovarian cyst to the intestines and the abdominal wall. A suppurating fistulous track extended between the caput coli and one loculus of the cyst, requiring a number of silk sutures to repair the opening in the intestine left after the enucleation of the cyst. Pus escaped into the abdominal cavity, and large handfuls of clotted blood were ladled out of


a hirge cavity in the pelvis. Pieces of the cyst wall and much debris remained behind at the completion of the operation.

There was considerable oozing and extensive traumatism produced by the separation of tlie wide-spread adhesions.

Pus from the cyst injected into a mouse killed it within twenty-four hours.

Notwithstanding all these complications the patient made a good recovery.


April, 1897.]


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67


Gynecological No. 4928J. A. E. S., admitted January 9, 1897. Single, age 35 years.

Complaint. Increasing size of abdomen, severe constipation, feeling of obstruction in abdomen. Menstruation began at 15 years, recurring every 28 days, 4 to 5 days duration, normal.

Family History. Negative.

Present Illness. Patient was always strong and well until four years ago; at this time she suffered with indigestion, and was treated by her physician for displacement of the uterus. She had an attack of peritonitis in September, 1895, which confined her bo bed four weeks. In October, 1896, she suffered


9 10 II 12 13 14 15 16 17


with " chills and fever," which lasted eight weeks. During the attack she passed pus from the rectum, her abdomen was swollen and very tender to pressure. Enlargement of the abdomen persisted after this attack, and has lately been increasing rapidly.

She suffers from stricture of the rectum, which followed an operation for hemorrhoids performed in 1892.

Present Condition. Body emaciated, complexion pale, expression anxious. Appetite good. Micturition normal.

Examination of heart and lungs negative. Temperature on admission 100.5° F., pulse 120.

Diagnosis. Suppurating ovarian cyst.



Case III.

Plain line indicates temperature. Broken line indicates pulse.


Operation by Dr. Kelly, January 16, 1897. Cystectomy.

Complications. Dense adhesions between cyst and intestine, fistulous opening between intestine and cyst. Pyogenic urea over bladder and anterior abdominal wall.

Puncture and evacuation through the abdominal incision of 2800 cc. of fetid pus, part of which escaped into the abdominal cavity. During enucleation of cyst it tore, allowing 150 cc. of pus to escape. Large hematoma filling lower pelvis opened and handfuls of thick putty-like blood were ladled out, in all about 200 cc. ITydrosalpinx and adherent ovary on the right side released, but not removed.

Adhesions between caput coli and tumor released, exposing


a fistulous track between the two 5 cm. in diametei-. Appendix thickened and twice its normal size, adherent to a black ragged area 2x2 cm. It was not removed, as it showed no disease and the patient's condition was very critical.

On right side the tumor was adherent to the anterior abdominal wall over an irregular area 6x3 cm., running down to cornu uteri. This area was scraped free of pus and lymph and covered with peritoneum from side to side.

Eagged area on colon covered in by base of appendix, which was sutured over it with interrupted catgut ligatures. Silk sutures were used to close the opening in the colon. Abdominal cavity thoroughly irrigated. Salt solution infusion (500 cc.)


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[No. 73.


under breasts, 500 cc. of salt solution left in the abdominal cavity. Pulse before operation 132, after 150.

First Day. On returning from operating room the pulse was 136, having dropped 14 beats in twenty minutes. Foot of bed elevated. Five o'clock in the evening pulse 128. Nine o'clock, 120. Twelve o'clock, 108. Patient comfortable and complaining of little pain.

Second Day. Pulse 108, temperatui'e 99.4° F. Patient complained of pain during the night, but slept three hours. Twelve o'clock noon, pulse 104, temperature 99.4° F. Six o'clock, pulse 104, temperature 100.4° F. Comfortable day. Foot of bed lowered.

Third Day. Passed an uncomfortable night. Pulse 104, temperature 90.4° F.

Afternoon, patient comfortable, pulse 100, temperature 99.8° F. Small liquid movement.


Fourth Day. Pulse 96, temperature 99° F. Considerable pain in abdomen.

Fifth Day. Temperature 98°, pulse 90. Patient had a comfortable night.

Sixth Day. Pulse 80, temperature 98° F.

Tenth Day. Convalescence has been uninterrupted. Dressiugs removed from abdomen, union of incision ^ler primam.

Patient sat up on her 20th day.

Bacteriological Examination. Cover-glass preparations showed many cocci and bacilli. Two cc. of pus injected into a guinea jjig produced death from septicaemia in twenty-four hours. Cultures from pus at the time of operation and from autopsy of guinea-pig became contaminated, consequently it is impossible to make a definite statement as to the species of organisms present. The fact, however, that the cyst communicated with the intestine makes it practically certain that all of the intestinal bacteria were present in the pus.


KEPORT OF FIVE CASES OF INFECTION BY THE BACILLUS AEROGENES CAPSULATUS (WELCH).

By Edward K. Dunham, M. D., Professor of Bacteriology, Bellevue Hospital Medical College, Neiu York.


Within the past year the writer has had occasion to study five cases of infection in which he believes the bacillus aerogenes capsulatus, described by Welch and Nuttal, and Welch and Flexner, either caused or hastened death.

In all but one of these cases the bacillus was found in material taken from the tissues of the patient during life.

The first case died on the 11th of March, 1896.

The patient was a woman, aged 23 years, who was admitted to St. Vincent's Hospital, New York, on the 7th of that month, and then gave the following history :

Three days before her admission to the hospital she had noticed a swelling beneath the lower jaw ou the left side of the neck. This swelling was the seat of throbbing pain.

From the time she first noticed this swelling she suffered increasing malaise, with chilliness, headache, loss of appetite, nausea, and pains in the back.

At the time of her admission she had diflBculty in swallowing, stiffness of the jaw, and pain, with a sense of constriction, in the throat. The left submaxillary triangle was swollen, pale and oedematous. There was no fluctuation in the swelling, though it appeared somewhat softer near the angle of the jaw. On the left side of the lower jaw some of the teeth were carious. The floor of the mouth bulged upwards and was tense. The left tonsil was enlarged, but showed no signs of inflammation. Temperature 101.2°, respiration 22, pulse 98.

Hot applications were made to the neck, and a mouth-wash of listerine prescribed. She also received morphine subcutaneously, and phenacetine and quinine by mouth.

The next day, March 8th, the swelling had increased considerably in size, swallowing was very difficult, and the patient suffered somewhat from dyspnoea. The neck was stiff and gave great pain on the slightest motion. Articulation was also interfered with. An exploratory puncture of the swelling failed to reveal the presence of pus.

On the day following, March 9th, the pain in the neck was


excruciating; swallowing was practically impossible; the voice was husky and the dyspncea marked. The swelling was hard and rapidly increasing in size, the pulse rapid and weak, the facies drawn and anxious. The urine was found to contain " 5 per cent." of albumen. On this day the patient began to show signs of delirium.

During the afternoon of the succeeding day, March 10th, cedenia of the glottis set in and at one time completely arrested respiration, but by means of an O'Dwyer tube and artificial respiration for a few minutes the patient was restored and the tube could be removed. The patient gradually lapsed into a comatose condition.

Ou this day an incision was made into the swelling and a small quantity of fetid, " very virulent-looking " pus obtained.

The next morning, March 11th, there was no discharge from the wound, but emphysematous crackling was felt at the angle of the jaw. At 6 A. M. the patient was dead.

The pus obtained on the 10th of March reached the Carnegie Laboratory on the 11th, accompanied by a message stating that it came from an acutely septic case in which infection with the anthrax bacillus was suspected.

Cover-glass preparations of the very fluid pus revealed the presence of cocci and of bacilli of large size.

Agar tubes iu four dilutions were prepared and placed in the incubator. Upon these two sorts of colonies developed, one of a yellow color and the other white. All of these colonies were made up of cocci, the bacilli in the pus having failed to grow. Subsequent cultures of the cocci served to identify them as the staphylococcus pyogenes aureus and albus.

On the same day that the pus was received bouillon tubes were inoculated from it and placed in a Novy jar, in an atmosphere of hydrogen, at 37° C. The next day the broth in these tubes was cloudy, and a hanging drop showed the presence of cocci and bacilli.

A guinea-pig was inoculated subcutaueously with 1 cc. of one


April, 1897.]


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69


of these bouillon cultures and died during the following night. At the autopsy the subcutaneous tissue was oedematous and emphysematous, and the fluid contained both cocci and bacilli, the lattei" predominating.

An effort was now made to isolate the bacillus and obtain it in pure culture for the purpose of identifying it.

A minute quantity of the broth culture used to inoculate the guinea-pig was distributed over the surfaces of several oblique agar tubes, which were placed in hydrogen in the incubator. No colony entirely devoid of cocci was found in any of these tubes, but one in which the bacilli greatly predominated was used to inoculate four rather dry blood-serum tubes, and upon these pure colonies of the bacillus were obtained and utilized for further study.

The bacillus was a large straight rod, about 0.9,a in diameter, with rounded ends, usually occurring singly or in pairs, but occasionally forming threads made up of four or five individuals. It stained readily with methylene blue, gentian violet and carbol fuchsin, and was very retentive of the dye when stained by Gram's method, resisting the decolorizing solution of iodine for ten minutes or longer. No spores were observed in any of the cultures, except those upon blood serum, though occasionally old agar cultures contained involution forms with an intimation of beginning sporulation, but without spores demonstrable by differential staining. In the subcutaneous fluid of animals it possessed a capsule, but this was usually not observed in cultures on artificial media.

It formed a moderately thin, moist, gray growth upon agar, and sometimes produced bubbles of gas in the condensation water at the bottom of the tube or between the agar and the wall of the tube.

Bouillon was rendered cloudy, and usually a few bubbles formed at its surface, while a gray sediment appeared at the bottom. In hanging drops, to which air had access, no evidence of motility could be detected.

Milk was coagulated in 24 hours and rendered acid, with a production of gas.

In all the media the bacillus proved to be a strict anaerobe.

The bacillus grew well in bouillon to which 1 per cent of glucose had been added, and these cultures evolved a considerable amount of gas when incubated in an atmosphere deprived of oxygen by means of potassium pyrogallate.

In order to determine the nature of this gas, six fermentation tubes containing glucose bouillon (1 per cent of glucose) were inoculated with the bacillus, and, after 24 hours, the gas collected in a eudiometer over mercury. 28.6 cc. of gas were obtained. This was subjected to the action of caustic potash, and when no more shrinkage in volume took place, air was introduced and an electric spark passed through the mixture. This was repeated until no more shrinkage in the bulk of the mixture resulted after the passage of a spark.

In this way the following approximate composition of the gas was determined :

Hydrogen 64.3 per cent.

CO2 27.6

Nitrogen (?) 8.1*

100.00 per cent.


On the 22d of March, i. e. eleven days after the pus was received at the laboratory, a guinea-pig was inoculated, subcutaueously, with a pure 24 hour culture of the bacillus in bouillon, one cubic centimeter being injected. The animal was found dead the next morning. The hair over the body was loosened so that it could be readily plucked from the skin, leaving it smooth and clean. The subcutaneous tissue was (Edematous, and so friable and filled with gas that the skin could be reflected from the abdominal wall without dissection. The gas burnt with a pale blue flame. The organs were of a dull gray color and very friable. The subcutaneous fluid contained great numbers of the bacilli surrounded by capsules, and apparently no other micro-organisms.

On April 3d, 23 days after obtaining the material from the hospital, another guinea-pig was inoculated, by means of a platinum needle, with a very small amount of a three-day culture of the bacillus on agar. The animal became very ill on the second day after inoculation and it was thought at that time that he would surely die in the following night, but he recovered after two days and remained well.

When injected into the blood of a rabbit, which was then killed after the lapse of a few minutes, the bacillus caused enormous swelling of the body of the animal within 20 hours, and the liver, kidney and spleen, as well as the subcutaneous tissue, were the seat of a very marked emphysema. The skin was rendered so tense by the accumulation of gas that it seemed on the point of rupturing.

The foregoing characters of the bacillus under study appear to identify it with the bacillus aerogeues capsulatus of Welch, the only point of difference being the spore-formation which was observed in cultures on blood serum. As the authors mentioned do not describe cultures on this medium, this spore-formation cannot be regarded as evidence against the identity of the two bacteria.f

A number of observations were made upon the resistance of these spores, and it was found that when taken from the condensation water of a blood-serum tube they could endure a temperature of 94° C. for one minute, but that an exposure of 5 seconds to the temperature of boiling water (99.5° C. at the time the observations were made) killed them. After being dried upon threads for 5 months and then immersed in water, they survived a temperature of 99° C. when subjected to it for one miuute.J

The vegetative form of the bacillus appeared to be killed by a temperature of 55° C. within one minute.

Ten mouths of desiccation and exposure to the air failed to kill the spores, which, at the end of that time, grew readily


  • The composition of the residual gas in the eudiometer was not

determined, but it did not contain CO3, for no diminution occurred when a fresh piece of caustic potash was introduced. This fact proves the absence of marsh gas or of any other hydrocarbon.

+ In a letter to the writer, dated February 19th, 1897, Dr. Welch states that the bacillus aerogenes capsulatus in his possession produced spores when cultivated on LoefHer's blood serum. This observation tends to still further establish the identity of the bacillus isolated by the writer.

i The author has observed that the spores of bacillus subtilis are much more easily killed by moist heat when freshly formed than after a lapse of time and drying.


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[No. 7.3.


when placed iu broth at the body temperature under anaerobic conditions, and those cultures caused the same extensive production of gas when injected into the blood of a rabbit which was soon thereafter killed, as did the earlier cultures obtained from the original material.

The spores stain readily in hot solutions of fuchsin in anilin water, and are not decolorized by a moderate exposure to the action of a 3 percent, solution of hydrochloric acid in absolute alcohol.

They have an oval shape and are usually situated near the middle of the bacilli in which they have been formed, their long axes coinciding with those of the bacilli. Their short diameter exceeds the diameter of the bacilli, so that the latter appear swollen at the points where the spores are situated.

The cultures containing the spores frequently contain involution forms of the bacilli and threads of the latter, which stain but faintly with methylene blue, and appear more attenuated than the individuals in fresh cultures on other media.

A partial antojDsy of this first case of infection was made on the day following the death of the patient by my assistant, Dr. Harlow Brooks, from whose notes I take the following data: General nutrition excellent. Rigor mortis present. There was extensive post-mortem discoloration about the neck on the left side, and the tissues in this region were the seat of marked emphysema.

The incisions in the neck made before the death of the patient were opened and a focus of suppuration was found, which apparently arose from the left tonsil. The walls of this abscess cavity were not well defined, but appeared necrotic, and this condition extended far into the fascise of the neck.

The liver, kidneys and spleen were examined, but did not appear emphysematous. Microscopical examination of bits of those organs failed to reveal the bacillus.

Sections from the organs of the rabbit into the veins of which the bacillus was injected, when stained by Gram's method, revealed the presence of the bacillus in great numbers in the blood-vessels. (See " I," temperature chart.)

The second case of infection occurred in a boy, seven years of age, who fell over a banister from the fourth to the ground floor of a house and sustained a compound comminuted fracture of the right humerus. This accident took jjlace at 3 j). m. on the 19th of September, 1896.

After being under the care of a physician not connected with the hospital for a couple of hours, the patient was admitted to the Gouverueur Hospital at 6 p. m., in a semi-conscious and delirious condition. He had a lacerated wound of the forehead as well as a fracture of the humerus. The arm was very dirty and its tissues much contused. The wounds were treated antiseptically and the patient sent to the ward iu a poor condition.

At 8 p. m. his temperature was 100°, respiration H, pulse 130 and very feeble.

On the 20th he was delirious throughout the day. On the 21st the dressings were removed and the arm and shoulder found to be much swollen, the skin over them tense and of a greenish bronze color, the discoloration extending over the pectoral region. There was no sign of emphysema noted at this time.


Free incisions were made and the subcutaneous tissues found in a necrotic condition. The wounds were washed with mercuric chloride and drained.

On September 22d the patient was still delirious, very weak, with a fluttering pulse. The dressings were again removed and fresh incisions made in the arm. The cedema had extended well into the pectoral region and down to the elbow, and at this time, I believe, some emphysema of the tissue was noticed. There was, however, no discharge from the wounds, owing to the prostration of the patient.

At 3 p. m. the patient died, just three days after the accident which resulted in the fracture of the humerus.

Some of the discharge from the incisions made on the 2l8t of September was collected in a sterilized test-tube and sent to the Carnegie Laboratory. It was delayed in transit and had an offensive odor when received. Cover-glass preparations showed it to contain cocci and a large bacillus, with I'ounded ends, positive to Gram's stain, and, in some fields, surrouuded by a capsule.

Slant tubes of agar were prepared and placed in the incubator; one-half in a Novy jar with pyrogallate of potassium, the other half with access of air.

After 48 hours the aerobic cultures showed only colonies of cocci, while the anaerobic cultures contained colonies in which both cocci and bacilli had developed. The latter tubes gave evidence of gas production, the agar being raised from the bottoms of the tubes. These colonies, though not pure, were used for the preparation of bouillon cultures grown under anaerobic conditions, aud, after 2-1 hours, they were cloudy and covered with a froth, due to the evolution of gas. Jn hanging drops both cocci and bacilli were found, the latter iu greater number. One cubic centimeter of one of these cultures was injected under the skin of a guinea-pig, and iu a few hours the animal showed signs of illness. Its fur was ruflled, the animal drew itself together and avoided the light. But it recovered, and after three days appeared to be quite well again.

A few drops of the same culture were introduced into an ear-vein of a rabbit and five minutes later the animal killed. The next morning its body was greatly distended by universal emphysema of the subcutaneous tissues. Puncture of the skin permitted the escape of a gas which burned with a pale blue flame.

On autopsy the abdominal cavity was found to contain much gas, aud the liver, kidneys, spleen, aud the mucous membranes of the digestive tract aud bladder were emphysematous.

Cover-glass preparations from the viscera and subcutaneous fluid demonstrated the presence of the bacillus, accompanied by a few cocci.

Agar cultures prepared from the organs of this rabbit formed the basis of future pure cultures, which served to identify this bacillus with that found in the first case. No spores were found in any of the cultures, but, unfortunately, the bacillus was not grown on blood serum.

No autopsy was performed on this second case of infection. (See " II," temperature chart.)

The third case of infection was a man, a't. 33, of alcoholic habits, who had suffered from urethritis on two occasions the last time three years before he presented liimself for final treatment at Belle vue Hospital.

When he was admitted to the hospital, on November 6, 1896, he had difficulty in voiding his urine, owing to a stricture of the urethra which could not be passed by instruments.

On December 5th, at 3.30 p. m., external urethrotomy \yas performed, and the patient did well until 2.30 p. m. on December 8th, when a sound was passed.

Twenty-one hours after this procedure a chill ensued, which was followed by severe pains in the joints and back, and from that time the patient rapidly grew worse and died on the 10th of December at 8 p. m.

At 9 p. m. on the day preceding death, an area of subcutaneous emphysema appeared over the front of the right thigh, and others over both shoulders. These areas increased rapidly in size up to the time of death and afterwards.

The following notes on the bacteriological examinations of material from this case and of the autopsy are kindly furnished me by my assistant, Dr. F. M. Jeffries, who conducted them. At 1 p. m. on December 10th, i. e. -1 hours before the death of the patient, three agar tubes were inoculated from the subcutaneous tissue in the emphysematous area on the thigh. These, although placed under anaerobic conditions, failed to develop, probably because of excessive acidity of the agar.

At the autopsy made 18 hours after death, cultures on agar and in bouillon were made from the heart, lungs, liver, brain, and the emphysematous area on the thigh. These cultures were incubated under anaerobic conditions in Novy jars with pyrogallate of potassium.

After 24 hours the cultures from all these sources had developed, with evolution of gas. They all consisted of bacilli resembling the bacillus aerogenes capsulatus. They wei'e not motile and stained well by Gram's method. All the cultures contained only this one bacillus, without admixture of other bacteria.

Intravenous injection of a bouillon culture in a rabbit which was killed five minutes later, resulted in the post-mortem changes already noted in the other cases just described.

The bacillus produced spores when cultivated on l)lood serum.

The autopsy on this case was pei'formed on December 11th, 1896, at 2 p. m.

The general nutrition was good.

Subcutaneous emphysema was noted, extending over the whole body, with a greenish discoloration over the thorax, right thigh and posterior surface of the body; most marked over the penis, scrotum and anus Puncture of the emphysematous area permitted the escape of gas, which burned with a faint blue flame.

The connective tissue under the skin of the thorax and abdomen was soft, pulpy and emphysematous. There were emphysematous areas on the pleurte and pericardium. There was general emphysema of the lungs. The cavities of the heart were distended, their walls soft and oedematous, and the blood they contained dark and fluid.

The liver was of a dark cliocolate color, soft and the seat of emphysema.


The spleen was dark plum-colored, extremely friable and emphysematous.

The kidneys were enlarged, showed subcapsular emphysema, and were plum-colored.

The mucous membrane of the bladder was extremely emphysematous.

The brain showed submeningeal emphysema, its substance was soft, the ventricles normal.

Microscopical examination of smears from the organs revealed the presence of large encapsulated bacilli resembling those found in the cultures. (See " III," temperature chart.)

The fourth case was a man, 23 years of age, who was admitted to the J. Hood Wright Memorial Hospital on the 6th of .January, 1897.

Four years ago he had gonorrhrea, which persisted for eight months, and three years ago he had another attack of the same trouble which lasted three months. Neither of these attacks was accompanied by symptoms pointing to inflammation of the bladder or testes.

Two years ago, i. e. about one year after the beginning of the second attack of gonorrhcEa, he felt pain on urination and noticed that the stream of urine was diminished in size. Shortly after this he had retention of urine, and was catheterized with some difficulty, and the urethral stricture then gradually dilated with sounds, the treatment lasting for two months. Since that time he had omitted all treatment.

At the time of his admission to the hospital the patient complained of pain on micturition, but there was no discharge from the urethra or increased frequency of urination. The urine was acid ; sp. gr. 1029; no albumen or sugar.

A urethral examination gave the following results :

No. 23 (French) bougie a boulu passed the meatus, but was stopped just bej'ond the urethral orifice.

No. 30 entered the urethra for a distance of 24 inches.

No. 25 slipped past a constriction at 23 inches, but was arrested at about 6i inches.

No. 30 and No. 15 sounds met with an obstruction at the same point.

No. 4 and No. 2 bougies also failed to pass that point, as did also a filiform bougie. Even a bunch of filiform bougies failed to demonstrate a passage, although, subsequently, after etherization in preparation for the operation, a filiform bougie was successfully passed.

External urethrotomy was pei'formed on January 9th, at 4.40 p. m., and a perineal drainage tube was left in the bladder, held in place by a silk ligature passing through the skin. The bladder and urethra were irrigated with saline solution and an aseptic dressing applied to the perineal wound. The urethra admitted a No. 34 (French) sound.

The patient was returned to the ward at 5.20 p. m., and a conducting tube, with its distal end immersed in a 2J per cent, solution of carbolic acid, was attached to the perineal drainage tube.

At 6.30 p. m. the patient vomited some blood. The dressings were found to be saturated with blood and were renewed. A slight oozing of blood from a wound in the bulb of the urethra was noticed. This had ceased at 9 p. m., and the patient then felt comfortable.


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[No. 73.


At 10.30 the bladder was agaia irrigated.

On January 10th the patient felt well and the bladder was draining nicely.

At 1.30 the urethra and bladder were irrigated with a warm saturated solution of boric acid. The anterior urethra contained some dark fluid blood which was washed away, and the perineal wound then dressed.

On the 11th and 12th of January the patient was doing well and the bladder was simply washed out.

The patient complained of some pain in the penis on the 13th, and at 3.30 p. m. sounds were passed down to the stricture, and gradually increasing in size up to No. 33 (French). The perineal drainage tube was then removed and a No. 33 sound passed through the entire urethra into the bladder, without difficulty. The perineal wound appeared healthy, and there was no discharge from the urethra except a small amount of blood which followed the manipulations. The auterior urethra was irrigated with saline solution and the perineal wound dressed. The patient felt somewhat chilly and received half an ounce of whiskey.

At 9.30, seven hours after the sounds were passed, the patient had a severe chill, lasting half an hour.

At 3.30 a. m., January 14th, a slight bleeding took place from the urethra.

At 8 a. m. pain in the left shoulder was complained of.

At 11 a. m. a catheter was introduced throiigh the perineal wound and about 3 ounces of bloody fluid having a foul odor evacuated from the bladder, which was then irrigated with saline solution. The bladder and anterior urethra were again washed out at 5 p. m., this time with a solution of permanganate of potash, jtW- '^^^ wound was dressed at this time and looked clean. The patient conn^lained of pain on pressure in the left buttock.

At 9 p. m. the pains in the shoulder and buttock had become severe, and at 11 p. m. these parts were found to crepitate on manipulation. The skin over these areas was not reddened and the parts were only slightly swollen. The area on the left buttock did not extend to the perineum, but was limited to the region about the trochanter and the external aspect of the ilium. The area at the shoulder was confined to the region overlying the left scapula.

On January 15th, at 4 a. m., the emphysematous areas had become somewhat larger and more swollen, firmer to the touch, and a little darkened in color. The patient, who was conscious, had an anxious expression and presented an extremely septic appearance.

At 7 a. m. the body was jaundiced, except over the emphysematous areas. Of these, that on the buttock looked much darker than before and was irregularly mottled with purple spots.

At 8.15 a. m. an incision, two inches in length, was made into the emphysematous area on the left buttock. A considerable amount of gas escaped through the wound, and a slight oozing of sanguineous fluid took place, but there was no sign of pus. Material for culture and bits of tissue for microscopical examination were taken from the walls of the incision.

At 9.30 the patient was still conscious, but died at 10.10


a. m., forty-five hours after the sounds were passed on the 13th of January.

Dr. Brooks performed the autopsy on this case, and the following account is taken from his notes :

The autopsy was made 5 hours after death, while the body was still warm.

Rigor mortis was marked; the general nutrition good.

Post-mortem discoloration was extreme from the pelvis up, and there was emphysematous crepitation over the abdomen, especially in the suprapubic region ; over the back, the buttocks, and the thigh, leg, and dorsum of the foot on the left side ; also, though in less degree, on the right side.

Puncture of the emphysematous areas permitted the escape of a gas which burned with a blue flame.

The abdominal wall was greatly distended, and when an incision was made the inflated intestines protruded.

The liver was of a light clay color and crepitated under the fingers. Its tissues were very friable, and filled with minute vesicles containing gas. The cut surface appeared oedematous.

The spleen was enlarged, of a dark purple color, and very friable.

The kidneys were enlarged; their capsules adherent.

The lungs were somewhat (Edematous.

The cavities of the heart were distended on both sides by fluid blood which contained bubbles of gas.

The autopsy was necessarily both hurried and incomplete, as the relatives of the patient refused to have any of the organs removed from the body.

During the autopsy agar tubes were inoculated by Dr. Brooks from the blood in the left auricle and from the tissues of the liver, spleen and kidney. A bouillon culture was also made from the blood. These cultures were then incubated in a Novy jar with pyrogallate of potassium, and after 14 hours developed pure cultures of a bacillus identical with those found in the preceding cases.

When grown upon blood serum these bacilli developed spores identical in character with those produced by the bacillus isolated from the pus from the first case.

Cover-glass preparations made at the autopsy from the same organs from which cultures were taken showed the presence of the bacillus.

One cubic centimeter of the bouillon culture from the blood was used to inoculate a guinea-pig subcutaneously. Within three hours the animal was manifestly ill, appearing to feel cold and to wish to avoid the light. It died within 30 hours, and at the autopsy presented marked emphysema of the areolar tissues and orsrans.

A rabbit was also inoculated, intravenously, with the bouillon culture, killed and put in a moderately warm place. The next day it showed the emphysematous condition of the subcutaneous tissues and internal organs which has already been described in connection with the other cases.

The material removed when the incisions were made into the emphysematous area on the buttock at 4 p. m. on the day of the death of the patient was used to inoculate agar tubes, part of which were cultivated with access of air, the rest under anaerobic conditions. Those exposed to the air showed no growth. Those grown with exclusion of oxygen contained


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a growth of a non-motile bacillus, positive to Gram, and morphologically resembling the bacillus aerogenes capsulatus. These cultures were lost and no further observations could be made, but as considerable work on this bacillus was being done at the time, no doubt exists as to the identity of the bacillus.

About 2i honi's after the death of the patient a sterile cotton swab was introduced into the urethra, and the moisture thus obtained used for the preparation of cultures.

Two bacilli developed in these cultures, and as they were both at least facultative anaerobes, efforts to separate that which proved to be a strict anaerobe were unsuccessful. One was smaller than the other and grew when air was admitted to the cultures. The other was morphologically identical with the bacillus aerogenes and did not grow in cultures exposed to the air. The smaller bacillus was thought to be the bacillus coli communis. A mixed bouillon culture of the two bacilli was injected into one of the veins of a rabbit's ear, and 15 minutes later the animal was killed. The next day the body was bloated and the large bacillus was found in the subcutaneous fluids, which were both emphysematous and (Edematous.

As a check upon this experiment a second rabbit was inoculated with a pure culture of the colon bacillus in the same manner and at about the same time as the first rabbit. The next day there were no signs of emphysema in its body. (See " IV," temperature chart)

The fifth case occurred in the private practice of a New York physician, who has kindly furnished the writer with the following facts concerning the history of the case.

The patient was a man, 73 years of age. His general condition was good, there being no organic trouble except some hypertrophy of the prostate.

On January 17th, 1897, the patient complained of pain and uneasiness in the perineum. This was traced to enlargement and tenderness of the prostate and of the tissues near the rectum in the median line.

The next day the pain was more severe, and a diagnosis of prostatitis was made. The pain was alleviated by means of opium and belladonna suppositories, and by the 20th of January the patient felt able to be about again.

That night, because of difliculty in voiding his urine, the patient passed a hard rubber catheter and drew some blood.

On the 21st, pain in the right ischio-rectal fossa was noticed, and the tissues at the site of the pain were found to be firmer than normal.

On the 22nd the pain in the right buttock was more severe. The patient was in bed, felt prostrated, and had a dry tongue and some fever. Temijerature about 101°.

On the 23rd the general condition was about the same as on the day before. Temperature 102°. There was increased harduess of the tissues of the right buttock, and the pain there was very great.

On the 2-l:th there was evidence of a pointing abscess in the buttock, in which the pain was excessive.

At midnight a sudden rupturing of this abscess into the neighboring tissues was felt, and immediately the scrotum became enlarged and the pain in the buttock was relieved.

The next morning, January 25th, the attending physician


found the scrotum emphysematous, with spots of gangrene upou it. Temperature 103°.

Later in the day the perineum was tense and distended, red and tympanitic. The scrotum was the size of a child's head (8 to 10 inches in diameter), dark in color, in places almost black, and cold to the touch. The skin of the penis was ballooned with gas and dark.

Very extensive incisions were made to the right of the raphe, from the penis to the tuberosity of the ischium. No pus was found, except at one point near the anus, where there was a cavity containing a dirty grayish-yellow pus of offensive odor.

The areolar tissue of the scrotum and penis were of an inky blackness and emphysematous, but contained no pus. A slight ojdematous condition prevailed in the deeper structures.

The tissues were irrigated with mercuric chloride and an iodoform dressing applied.

On the following day, January 26th, the emphysema had extended over the pubes and the hypogastric region, the skin being raised about half an inch. The color of the skin over this area was either normal or had a pinkish blush.

Two free incision* were made to evacuate the gas, and it was discovered that the subcutaneous areolar tissues were blackened. No pus was present.

A portion of this black slough was removed with sterile instruments and put in a sterilized bottle for examination.

On the 27th the emphysema and necrotic area had extended upwards to the sternum, and laterally to the shoulder-blades, and fresh incisions were made. A single focus of pus found above the navel.

In all the places where prior incisions had been made the sloughing had extended so as to include the skin, but without the formation of pus.

The patient lapsed into a low typhoid condition, then into coma, and died on the 31st of January.

Cover -glass preparations of the material removed from this patient on January 26th were examined on that day at the Carnegie Laboratory, and showed the presence of three species of bacteria : 1, a large bacillus, resembling the bacillus aerogenes capsulatus ; 2, a more slender bacillus; 3, streptococci.

The slender bacillus was identified as the bacillus coli communis, and when obtained in pure culture, produced no emj)hysema in the body of a rabbit killed shortly after the injection of the culture into a vein of the ear.

Experience with the mixed cultures, obtained from the cotton swab used to collect material from the urethra in the fourth case, had shown the difliculty of separating the bacillus aerogenes capsulatus from the bacillus coli communis. Without waiting, therefore, to obtain pure cultures of the large bacillus found in this ca^e, a mixed bouillon culture of the two bacilli was injected, intravenously, into a rabbit, which was shortly afterwards killed. The usual post-mortem emphysema was produced within a few houri?, and from the subcutaneous fluids pure cultures of the bacillus aerogenes capsulatus were finally obtained. These, unfortunately, died out in future cultures, owing, it is thought, to the reaction of the agar which was employed as a culture medium and which was found to be strongly acid.


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No accurate temperature chart could be obtained in this case, and there was no autopsy.

The foregoing cases appear of interest as showing that the bacillus aerogenes capsulatus is sometimes capable of rapid development within the human body, during life, and of causing an acute and speedily fatal infection.

They serve also to show that the bacillus is of pretty wide distribution ; for within eleven months these five cases have come under the observation of a single individual and were, notwithstanding, wholly unconnected with each other, occurring as they did in various parts of the city of New York and coming under the care of different physicians.

The mode of infection was not the same in all of the cases. But it is a striking circumstance that in three of the cases the infection started near the perineum after injury to the urethra, and in two of these the bacillus aerogenes capsulatus was associated, as far as the wound was concerned, with the bacillus coli communis.

In the case in which the site of infection was the wound of


a compound fracture of the humerus, the history states that the wound was covered with dirt. This fact naturally leads to the suspicion that the bacillus aerogenes capsulatus, like so many of the anaerobic bacteria with which we are familiar, may occur in the soil ; and the occasional production of spores, noted in the account of the first case and also observed in similar cultures from the fourth case, might readily explain the persistent vitality of the species under conditions which would otherwise be fatal to it.

From the soil to the intestinal tract of man would be a simple route by which the bacillus might gain access to the human body and find conditions not unfavorable to its development and, perhaps, spore-formation.

If the bacillus once gained access to the intestinal tract its presence in the perineal region couldoccasion no surprise. And if, through the wounded urethra, or some other lesion, it once reached the subcutaneous tissues and possessed sufficient virulence, the gangrenous process illustrated by these cases would ensue as a matter of course.


OBSERVATIONS TO DETERMINE THE MOTILITY OF THE BACILLUS AEROGENES CAPSULATUS

UNDER ANAEROBIC CONDITIONS.

By E. K. Dunham, M. D.


Bouillon cultures of the bacillus were studied in flattened capillary tubes from which the oxygen of the air had been absorbed by means of pyrogallate of potassium. Although these cultures were examined at intervals varying from 15 minutes to 24 hours, at no time could any evidence of motility on the part of the bacilli be detected.

The details of the experiment were as follows :

The cultures were obtained by putting threads, containing spores of the bacillus, which had been kept in a dry state for 11 months, into tubes containing sterile bouillon. Three such tubes were prepared, and after incubation in a bottle containing pyrogallate of potassium, they all showed an abundant growth of the bacillus within 24 hours. These cultures proved to be pure. One cubic centimeter of one of these cultures was then mixed with about 3 cc. of fresh sterile bouillon, in order that the bacilli present might have a good supply of nourishment, and this mixture used for the observations on motility.

The capillary tubes were prepared by heating a piece of glass tubing, about 8 inches long and with a bore measuring about i of an inch, strongly in the middle, then bringing the two halves parallel to each other and separating them about two inches (Fig. 1). In this way a U-shaped tube with a flatted bend was obtained. The limbs of this tube were then bent at right angles, so that their axes were in the same straight line. The ends of the tube were plugged with cotton and the tube sterilized by dry heat (Fig. 2).

A few moments before use, the middle of the flattened portion of the tube was heated until quite soft, and then rapidly drawn out to form a capillary tube. This was then broken in the centre and the end immersed in the bouillon culture.


A portion of the culture quickly filled the capillary part of the tube for a distance of from 2 to 3 inches. The end of the capillary tube was then sealed in the edge of the flame of a Bunsen burner. Enough pyrogallic acid to closely fill about 1 inch of the tube was then introduced into its large end, this was moistened with a 50 per cent, solution of caustic potash in water, and then the end of the tube was closed by means of a piece of rubber tubing plugged at the other end with a bit of glass rod (Fig. 3).


Fto. I.


Fig. <3.


F,g.l.

When prepared in this way the capillary tube containing the culture was so flat that it was possible to examine the whole contents of the tube under a Jj oil immersion objective.

Eight such tubes were prepared, and four of them preserved at the room temperature, the other four being placed in the incubator where the temperature was maintained at 35° C. They were examined at intervals of 15 minutes, 1 hour, 3J hours, 21 hours and 34 hours. In no case could any locomotion of the bacilli be detected.

After two and a half hours the bacilli were present in


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greater numbers than when the cultures were first introduced into the tubes, showing that the conditions were favorable for their multiplication. At the end of 24 hours the number had increased enormously, and there were two small bubbles of gas in one of the tubes which had been kept in the incubator. It might, perhaps, be thought that the chilling, occasioned by removing the tube from the incubator for the purpose of examining its contents under the microscope, would be sufficient to check the locomotion of the bacilli, before a clear


view of them could be obtained. That this was not the case is shown by the fact that in all the tubes the bacilli soon subsided to the bottom, leaving the bouillon above them free from bacilli. If the tube was turned a little about its long axis and kept in that position for a time, the bacilli settled towards the lower side of the tube.

These observations appear to demonstrate that this bacillus does not possess the power of locomotion, even under anaerobic conditions.


MULTIPLE TUBERCULOUS ULCERS OF THE STOMACH, WITH A REPORT OF THREE CASES.

By Alice Hamilton, M. D.

[From the Pathological Laboratory of the Johns Hopkins University and ITospital.]


Tuberculous ulcer of the stomach is conceded by all writers on pathology to be of extremely rare occurrence, some indeed of the earlier ones considering that organ almost immune from tubercular infection. Again, some few of the earlier writers claim to have found it with comparative frequency in the autopsies of tubercular subjects ; but as their results vary so greatly from those of the large majority, one is forced to believe that they have included cases of simple ulcer among the number. Forster, Rokitansky, Cornil et Ranvier, Ziegler, Orth, Birch-Hirschfeld and Klebs are unanimous in declaring the extreme rarity of this lesion.

Single cases purporting to be of this disease are reported from time to time in the literature, but it is imjjossible to accept all of these as actually cases of tubercular ulcer. As the greater number were reported before the discovery of the bacillus tuberculosis, one does not expect to find the diagnosis resting on its presence; but in many of these cases no histological examination was made, and in others no details of such examination are given. All such cases must be dismissed as doubtful or merely probable. Only those can be classed as proven where the report shows by a detailed description of the results of the microscopic examination that the histological characteristics of tubercle were present and which were confirmed or not, as the case may be, by the demonstration of the bacillus tuberculosis.

The earliest of these is Litten's. It was a case of tuberculosis of lungs and peritoneum with no lesion in the intestines, but with a single ulcer in the anterior wall of the stomach, which on microscopic examination showed typical caseating tubercles with giant cells. Talamon also describes tubercles found in the walls of ulcers in the stomach of a child which had died of pulmonary tuberculosis. In this case the ulcers were seven in number, scattered over the surface from cardla to pylorus. Brechemin's case resembled Litten's in presenting no lesion in the intestines. There was a single ulcer— its location not mentioned — with thickened edges and a floor covered with nodular elevations consisting of " caseated masses surrounded by embryonic and lymphoid cells." Eppinger's two cases are described in great detail and are interesting in being the first cases of multiple ulcer which have been accurately reported. Here, too, the intestines in both cases


were intact. The first one was a case of general miliary tuberculosis, and the stomach contained many miliary tubercles as well as innumerable small losses of substance in the mucosa. These ulcers had hard, elevated, regular " rampart-like " walls, and their bases were covered with whitish granulations, which on section proved to be caseated. His description of the microscopic appearances leaves nothing to be desired in either of the cases, the second resembling the first very closely.

Barbacci's case showed tuberculosis of lungs, peritoneum and intestines, besides which the stomach contained five ulcei'S near the pylorus, two of them having a diameter of 6 cm. These showed nodules of embryonic cells with caseation in the centre. The case of Pozzi is not quite positive. He found an ulcer near the greater curvature in the stomach of a man who had succumbed to pulmonary and intestinal tuberculosis. The walls and base of this ulcer showed no nodules, only "diffuse tubercular tissue." As it was impossible that the diagnosis here should be confirmed by the discovery of the tubercular bacillus — the case was published in 1868 — it must be regarded as somewhat doubtful. Duguet's case of a single ulcer near the pylorus in a phthisical patient is so obscurely described that one can come to no definite conclusion about it. Marfan rejects it in his resume of tubercular lesions of the stomach.

Coats was the first to demonstrate the bacillus in a gastric ulcer. His case, a child with pulmonary tuberculosis, presented numerous losses of substance in the mucosa of the stomach, and the examination showed not only the histological elements of tubercle, but also the specific bacillus. Serafini, Musser and Mathieu et Remond also found the bacillus in their cases. Mathieu et Remoud's case goes to swell the list of those which showed no lesion in the intestine.

J. Kiihl reports four cases from the Pathological Institute at Kiel. He examined all for the tubercle bacillus, but failed to demonstrate it in the two older specimens which had been a long time in the museum. Nevertheless, the histological appearances in the first of these cases point quite positively to tuberculosis; in the second his description is too scanty and obscure to place it above question. The third and fourth instances, which were recent, are described as containing caseating nodules with tubercle bacilli. R. G. Hebb and G. Lava


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report each a case of single ulcer — at the lesser curvature and at the pylorus respectively — and describe the microscopic findings as tubercles with caseation and giant cells. It is to be regretted that these observers failed to make any search for the bacillus tuberculosis. This omission is still more striking in Letorey's otherwise exhaustive description of a case of diffuse ulceration near the pylorus. He states that tubercle bacilli were found in the lungs and in the diseased part of the femur, but seems not to have looked for them in the ulcers, where he, however, found typical caseating nodules.

In the following cases it is difficult to decide whether the lesions described are really tubercular or not, the authors having satisfied themselves of the correctness of their diagnoses, but having failed to establish them by giving the facts on which they were founded. So, for instance, Hattute merely states that his case showed "elements of tubercle in the granulations." Lorey, Anger, Matthieu, (Jazinaud Beadles give no details at all. Finally, a large number must be utterly rejected as, according to the explicit statement of the authors, no microscopic examiuation was ever made. Such are the cases of Bignon, Paulicky, Chvostek (four), Hebb (second case), Lauge, Barlow and Quenu, which last rests for its diagnosis on a mere statement of the author, no description of its macroscopic appearance being given. Several others which have been placed in the list of tubercular ulcer were really miliary tubercles in the walls of the stomach. Kiihl's fifth case is an example, also Earth's. Labadie-Lagrave's case showed a cicatrix near the lesser curvature, its tubercular origin being merely hypothetical. Oppolzer's is described as a perforating ulcer connecting stomach and colon, supj)osedlyof tubercular origin, but it was impossible to say in which organ it originated. This covers all of the authentic literature so far as I have been able to discover, and it will be seen that it contains fifteen undoubted cases and nine more which are probable but not proven.

The two cases which I wish to report are, I think, undoubtedly tubercular, although neither could be considered as strictly typical. Indeed, the histological findings in the second case were so little suggestive of tuberculosis that, had it not been for the discovery of the tubercle bacillus, I should not have ventured to class it as tubercular, but the large numbers of bacilli present leave no doubt that they were the prime factor in causing the ulcerative process. The first case, which contained very few bacilli, presented an appearance that was much more characteristic of tuberculosis. I will omit the histories of these cases, which offered nothing of special interest, merely stating that both patients were admitted to the Johns Hopkins Hospital, to the service of Ur. Osier, in the advanced stages of pulmonary phthisis. The autopsies were performed by Dr. Flexner, from whose reports I will give merely the essential points.

Case 1. Colored female, aged 30 years. The right lung contained near the apex a cavity about the size of a small walnut, with smooth walls; the lung tissue adjacent was densely infiltrated and converted into a caseous mass. In the lower portions of the upper lobe, beneath the anterior surface and near the middle line, a small cavity existed with smooth walls which communicated freely with the bronchi. Its walls were caseous, and


adjacent to it were large caseous masses surrounded by oedematous and congested tissue, which often presented a gelatinous appearance. The upper portion of the lower lobe was taken np by a series of cavities, more or less communicating, the deepest of which extended almost to the pleura, and was separated from this only by thin granulation tissue in which could be seen many opaque tubercles. Over this cavity the two layers of the pleura were adherent. The dependent portion of this lobe anteriorly was drawn out to a tongue-like aj)pendage in which were caseous masses, the intervening lung tissue presenting a gelatinous appearance. Firm, dry and caseous tissue surrounded the cavity in the upper lobe, and most of the remainder of this lobe was converted into similar tissue. The lower lobe contained scattered caseous foci, while the pleura covering all of the left lung was scattered over with gray and opaque tubercles. The bronchi, larynx and trachea showed numerous superficial losses of substance reaching only through the mucous membrane. This ulcerative process in the larynx extended to the mucous membrane of the mouth and tongue, but did not pass to the esophagus. The bronchial lymphatic glands were pigmented, enlarged and caseous. Tubercles were observed in the liver and kidneys.

The intestines were the seat of numerous ulcerations, which occurred at intervals, beginning 165 cm. below the duodenum and extending to within 10 cm. of the rectum. They were partly circular, partly elongated — " girdle-ulcers " — and penetrated to the muscular coat. In many, small tubercles were visible in the depth. On the peritoneal surface a few tubercles were seen. The appendix vermiformis was free from ulceration.

The stomach showed a large number of losses of substance, from 115 to 120, scattered over the entire organ, but most thickly on the anterior aspect near the greater curvature. These ulcers were round or oval, usually smaller than a penny, with rounded thickened edges, generally smooth and undermined for a variable distance.

The chief interest for our purpose centers in the ulcerations existing in the stomach. Our studies embraced the examination of many of these, often in serial sections, both with respect to their pathologic histology and to the presence of tubercle bacilli. Ulcers of various sizes were sectioned, stained and examined microscopically. The details are purposely omitted. The ulcers vary in their histological appeai-auces, depending somewhat upon the extent of their development. Even in the youngest and most superficial the glandular elements are much disturbed, and a considerable proliferation of cells has taken place in the mucosa. The cells are small, round and lymphoid in type, but among them are also some which have the character of epithelioid cells. The deeper ulcers show a greater number, even a preponderance, of cells of an epithelioid habitus, and an arrangement at times into nodules of the size and I'oughly of the appearance of miliary tubercles, whose centres are formed by epithelioid, and whose peripheries by lymphoid elements. Giant cells were not discovered. On the other hand, necrosis of cells existed with fragmentation of nuclei, and, within the new tissue, even larger areas suggesting definite caseation. The nodules with central necrosis were sometimes in the mucous membrane, perhaps in


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the overhanging edges of the ulcers, and again upon the floor formed by the submucosa, which was always found when exposed to be infiltrated with new cells, partly lymphoid, partly epithelioid in character. The thickened, undermined edges showed an increase of spindle-S'haped cells, suggesting a new growth of connective tissue, forming at times a decided band. Tubercle bacilli (Ziehl-Neelsen method of staining) appeared in small numbers along the free surface of the ulcers, and singly, imbedded in the tissues, among the clusters of epithelioid cells.

Case 3. Male, colored, age fifty years. The right lung was bound by adhesions to the chest wall and the diaphragm, and the lobes were bound to each other. On section the whole lung was quite consolidated. Old fibrous processes extended in all dii-ections through the lung, but they were most abundant posteriorly and at the apex. Small foci of caseation partly calcified were found, and in addition actual cavities lined with thin pyogenic membranes, the largest of them not exceeding the size of a walnut. The bronchial glands were enlarged, caseous and partly calcified.

The left lung, on the other hand, was free from adhesions except at the apex, the upper lobe was retracted at the apex, slaty in color and contained caseous masses, but elsewhere this lobe was quite smoothly consolidated. The lower lobe was voluminous, congested, containing very little air. In some smaller branches of the pulmonary artery partly decolorized thrombi existed, without infarction. Both bronchial and mediastinal glands were enlarged and caseous.

The small intestines were free from ulceration, but in the patches of Peyer in the ileum near the valve there were several elevated gray nodules, about the size of bird-shot or a little larger, with central depression, doubtless small tubercles with loss of substance in the centre. The large intestines were free; the appendix vermiformis contained about its centre an elevated grayish nodule similar to those in the ileum.

The mucous membrane of the stomach was congested and covered with sticky mucus, and along the greater curvature, almost over its entire extent, small losses of substanceoccurred, 70 to 75 in number. They presented worm-eaten edges and uneven bases, which sometimes, but rarely, were covered with small granulations. They extended usually only partly through the mucosa. The follicles of the oesophagus were enlarged, but without ulceration.

The histological and bacteriological examinations of these ulcers were carried out in the same manner as in the preceding case, fourteen of the ulcers in all being subjected to study. For this purpose ulcers of various sizes were chosen. With the exception of two or three, those examined involved only the upper layers of the mucous membrane, and the deepest ones did not extend beyond the muscularis mucosae. The edges of these ulcers were never deeply undermined, and the infiltration of the mucous membrane passed a very little way only beyond the ulcerations. In general the appearances presented were those of superficial and small ulcerations, whose floor was formed by the infiltrated mucous membrane, still showing glands or vestiges of glands, but in which the proliferation of cells had so altered the latter that they were often with difficulty recognizable. The new cells consisted chiefly of


the lymphoid variety, and they were diffusely scattered, but epithelioid or larger cell elements were not entirely absent. Only once was a perfectly distinct nodule, the size of a miliary tubercle, discovered, and this consisted of epithelioid cells more centrally and lymphoid more peripherally placed. On the other hand, in the floor of the ulcer it was possible to distinguish more nodular formed masses of lymphoid and epithelioid cells, but definite and typical tubercles, in the usual sense, were entirely wanting. The free surface of the ulcers showed more or less necrosis ; the deeper layers, which were in an excellent state of preservation (the tissue having been perfectly fresh), were quite free from such indications. Tubercle bacilli were present in great numbers; in no section were they wanting, and often they occurred in great clumps. The main masses were on the free surface of the ulcers, but they were also found deejjer down among the glands or within their luniina.

The foregoing cases seem to possess sufficient interest to warrant recording them, even though it is now admitted generally that the stomach at one time or another becomes directly involved in tuberculosis of the alimentary tract. It is interesting to consider for a moment a fact alluded to by many writers, that there is a want of correspondence between the appearance of lesions of a tuberculous nature in the stomach on the one hand and in the intestine on the other. While in the great majority of cases the latter shows great disposition for the development of tuberculous ulcers, it is interesting and striking to see how often in the cases reported in the literature, where ulcers existed in the stomach, the intestines entirely or almost entirely escaped. Every pathologist must be imjjressed with the unexpected variations in the localizations of tuberculous lesions, and must have observed instances in which the alimentary tract entirely escaped infection when the conditions seemed most favorable for it. It is impossible at the present time to give any satisfactory explanation of such occurrences.

Concerning the multiple nature of the ulcers in the two cases discovered above, they are in this respect, compared with other cases (except Eppingei-'s), peculiar. It is questionable whether they may be considered as having shown any special predilections for situation, excej)t in the second case to avoid the pylorus, apparently the most common seat of single ulcers. Two points may be considered in this connection, one of which is borne out by the bacteriological examination of the second case. The size of some of the ulcers and their limitation to the mucous membrane agree not a little with the small erosions following ecchymoses into the mucosa, the socalled hemorrhagic erosions. The absence of a specific histological structure peculiar to tubercle, in many of the more superficial losses of substance, is not inconsistent with such an origin. That such erosions are very common in many diseases is of course well known, and it may therefore with projn'iety be asked whether a part of the ulcers in the second case do not owe their origin to this cause, and the tubercle bacillus is responsible only secondarily for a further destruction; the production of those lesions more nearly resembling histological tul)ercles. Eppinger long ago declared that the u'sophagus was invulnerable to the tuberculous virus, unless a


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previous lesion existed to enable it to get a foothold; and while this statement has perhaps been disproven, yet that such a previous injury may act as a predisposing cause is more firmly established now than when he wrote (see Cordua). And if for the oesophagus, it may be asked why not for the stomach? The facts in our second case point more towards such a view, namely, that many small erosions, probably of hemorrhagic origin, existed in the stomach, some or all of which became invaded by tubercle bacilli swallowed with the sputum, than that they owe their production to a direct invasion, in the absence of a previous lesion, of the mucous membrane of the stomach, by the bacillus tuberculosis.

In closing I wish to express my gratitude to Dr. Flexner for the advice and assistance most kindly given me in the course of this investigation.

Addendum.

After the completion of the above report, a third case of gastric ulcer came under observation, which proved also to be of tubercular origin, and the specific character of which was far more easily determined than in the other two cases. The lesions here conformed in every way most closely to the usual type of tubercular ulcerations. The ulcers wei-e in this case but two in number, of large size, and accompanied by the formation of tubercles which were evident even to the naked eye.

Vase 3. The patient was a colored girl of eleven years of age. She entered the medical department of the Johns Hopkins Hospital (service of Dr. Osier) on June 16th. Tubercular peritonitis was diagnosed, and she was transferred to the surgical side, where the diagnosis was confirmed by an exploratory operation, the peritoneum being found covered with miliary tubercles and the intestines matted together. The patient recovered from the operation and lingered until December, when death occurred. The autopsy was performed by Dr. Livingood, from whose report the following extracts have been taken.

The body was much emaciated. Extending from below the costal margin to a point opposite the umbilicus was the scar of an imperfectly closed incision, the floor of which consisted of a sloughing surface covered with pus. Near the umbilicus the tissues were darkened and necrotic in appearance. On attempting to open the peritoneum, the transverse colon and the upper part of the omentum were found completely coherent. Below, the intestines were closely matted together by fibrinous and fibrous bands, which could be stripped apart, though with difficulty, especially at the umbilicus. The parietal layer of the peritoneum was thickened and studded with conglomerate and miliary tubercles. The peritoneal cavity contained a large amount of turbid, yellowish-white fluid with fine flocculi. It had a slightly faecal odor. The serous coat of the intestines was studded with numerous caseous tubercles, usually about the size of a cherry-stone, but ranging larger and smaller. The appendix vermiformis was so matted in the mass that it could not be found.

The anterior mediastinal and the lower cervical glands wei-e enlarged and caseous. The visceral and parietal layers of the pleura on the right side were studded with caseous tubercles, some of which reached the size of a beau.


The pleural cavity was partly obliterated by fibrous adhesions. The lung contained in its apex numerous small nodules, some of them caseous ; it was congested over the remainder of its extent, and small tubercles could be seen and felt scattered through it. The left pleural cavity was completely obliterated, and the lower lobe of the lung could not be freed from the diaphragm, but had to be removed with it. Miliary tubercles were scattered over both layers of the pleura, especially thickly along the lines of the ribs. A large area of caseation was formed where the lung was in contact with the diaphragm, and this process seemed to have extended directly through the diaphragm to the spleen and liver beneath. The upper lobe of the left lung showed more extensive tuberculosis than did the right lung, being filled with numerous tubercles in all stages of caseation, but without definite cavity formation. Small nodules were scattered through the lower lobe, which was much congested and, at its lower extremity, in the early stage of consolidation.

The spleen was adherent to the diaphragm and to the parietal peritoneum. Its capsule was thickened and was the seat of large caseous tubercles, but there were no distinct tubercles in the substance. One small caseous tubercle was found in the right kidney. The mucous membrane of the uterus was the seat of a number of yellow and gray miliary tubercles. Both tubes were enlarged and adherent to the surrounding structures. Some of the lymphatic glands in the broad ligament were caseous, and the vaginal mucous membrane contained a single tubercle. The caj)sule of the liver was covered with numeroiis minute tubercles, and others were found in the substance of the organ. The pancreas was closely adherent to the caseated retroperitoneal lymph glands, and its substance showed large caseating areas.

The stomach was adherent to the transverse colon, the pancreas, and to the mass of enlarged peripancreatic lymph glands. The serous coat was covered with small and large caseous tubercles. Midway between the pylorus and the cardia on the posterior aspect of the lesser curvature, was a large, irregularly oval, crater-like erosion, 3 cm. by 2 em. in size. The edges were raised and somewhat undermined and more deeply congested than the surrounding parts. The floor was irregular, the deepest part of the crater measuring 8 mm., while the remainder was formed by projecting caseous tubercles. Directly behind this ulcer was a caseous lymphatic gland, so closely adherent to the stomach wall at this point that it was impossible to tell whether or not it formed the floor of the ulcer. A second smaller erosion was found above this one, in the middle of the lesser curvature. Its edges were slightly elevated, and in one place deeply undermined, the floor being formed by the muscularis. Here and there scattered through the mucous membrane were minute grayish white and yellow points looking like, but not proven to be, miliary tubercles. In the duodenum, just beyond the pyloric orifice, was a large ulcer with caseous tubercles covering its base; a similar but still lai-ger one was found in the cajcum, and smaller ones scattered through the small intestines.

In the microscopic examination of the larger of the two gastric ulcers, the section passed also through the adherent lymph gland, which was found to be completely necrotic. It


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was intimately adherent to the stomach, separated only by the remains of the muscular wall from the caseous masses within the stomach wall proper. The mucous membrane for quite a distance around the ulcer was infiltrated, becoming more or less necrotic at the edges, which were elevated and undermined. The deepest part of the ulcer had for its floor the muscularis, but the walls were formed by large caseous tubercles, some of which were completely necrotic. In the overhanging edge, which was formed by mucosa, and throughout the mucosa generally, were found small tubercles which, for the most part, had originated in the submucosa or muscularis mucosse. They represented all stages of tubercle formation. Giant cells were present in great numbers. Sections stained by the Ziehl-Neelsen method showed numerous tubercle bacilli, both in the superficial and deep layers.

In this case the question naturally arose whether or not the ulcerative process in the stomach was merely secondary, having been caused by the adherent lymph gland which had ulcerated through to the free surface. The microscopic examination proved, however, that the process in the stomach was quite independent in its origin, as the still intact muscular wall could be traced along the whole extent of the ulcer between it and the caseous gland behind.

Bibliography. Litten : Virchow's Archiv, 1876. Talamon ; Progres Medical, 1879. Brechemin: Bull. d. 1. Soc. Anat., May 1879. Eppinger: Prager Med. Wochenschrift, 1881.


Barbacci : Lo Sperimentale, May 1890.

Coats : Glasgow Med. Journal, 1886.

Serafini : Annal. clin. del Osp. di Napoli, 1888.

Mathieu and Remond : In Letorey's Thesis, Paris, 1875.

Musser: Phila. Hosp. Reports, 1890, I.

Kiihl : Thesis, Kiel, 1889.

G. Hebb: Westminst. Hosp. Reports, 1888, III.

Lava: Gazz. Med. di Torino, 1893.

Letorey: These, Paris, 1895.

Hattute: Gaz. des Hop., 1874.

Lorey: Bull. d. 1. Soc. Anat., 1874.

Anger : In Marfan's Thesis, Paris, 1887.

Marfan : These, Paris, 1887.

Matthieu : Bull. d. 1. Soc. Anat., 1881.

Cazin : In Fernet's article. Bull, et Mem. d. 1. Soc. Med. des

Hop., 1880, t6me XVII. Beadles : British Med. Journ., 1893, II. Duguet: In Spillman's These, Paris, 1878. Paulicky : Berlin Klin. Wochenschrift, 1867. Chvostek : Wieu. Med. Blatt., 1882, V. Lange: Memorabilien. Heilbroun, 1871, XVI. Barlow : Path. Soc. London, 1887. Pozzi : Bull. Soc. Anat., 1868. Labadie-Lagrave : Bull. Soc. Anat., 1870. Oppolzer: In Marfan's These, Paris, 1887. Quenu : In Marfan's These, Paris, 1887. Oordua: Arbeiten aus dem pathalog. Institut in Gofctingen.

Berlin, 1893.


STUDIES ON TRICHINOSIS.


By T. R. Brown.


[Abstract of remarks and discussion before i

The clinical history of the case which forms the basis of these remarks resembles in some respects the classical picture, though the symjjtoms were unusually mild. The patient, a man 23 years of age, was admitted to the hospital on March 3, 1896, complaining of general muscular pains. He had been ill six weeks, and for the two weeks before entry the pain had been so severe that he had scarcely been able to move about. There were irregular fever and extreme muscular tenderness, particularly in the arms and legs. The diagnosis of a myositis, probably due to trichinosis, was made and confirmed by the finding of actively motile trichinfe in pieces of muscle removed from the arm.

He remained in the hospital for over two months, being discharged well.

During his stay in the hospital the blood was examined daily. The number of leucocytes per cm. was determined and a differential count was made of the various forms; frequent examinations of the urine were made with quantitative determinations of the uric acid, urea and total nitrogen. The two small pieces of muscle which were removed were subsequently subjected to careful microscopical examination. The results of the studies may be summarized as follows:

(rt) The blood. The study of the blood was carried on con


the Johns Hopkins Hospital Medical Society.]

tinnally during the course of the disease, a determination of the leucocytes and a differential count of the various forms of leucocytes being made daily. The result of these observations showed : (a) A gradual rise of the proportion of eosinophiles, reaching 68.2 per cent — 35 per cent, higher than any previous record — and from this point a gradual decline to 16.8 per cent, on the patient's discharge; (b) a coincident depression of the polymorphonuclear neutrophiles, reaching at one time 6.6 per cent., while for two weeks these forms showed an absolute decrease in the blood, notwithstanding (c) the marked leucocytosis, reaching on some occasions above 30,000 per cubic millimetre.

In fact, the neutrophiles and eosinophiles showed at all times an inversely proportional relation, and the eosinophilic rise could be seen to be distinctly at the cost of the neutrophiles, the other forms showing relatively little fluctuation.

The presence of such quantities of eosinophiles suggests their possible diagnostic value in trichinosis, and perhaps, if it be found on further studies to be characteristic of this disease, may help to clear up the cases which are regarded intra vitam as rheumatic in nature and which, years afterward, the autopsy table shows to have been cases of trichinosis.

As an association has for a long time been noted between


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the eosinophiles and the Charcot-Leydea crystals, various experiments were made with the blood which contained such large quantities of eosinophiles, to see if the crystals could be derived directly from these cells. In all cases, however, the results were negative, seeming to show that the crystals are, at least, not direct crystallization products from the eosinophiles, but that something besides the presence of these cells is necessary for their formation.

{b) The uruie. The quantitative determinations of the uric acid, urea and total nitrogen were carried on mainly in connection with the ideas of Horbaczewski, that the uric acid, derived from the destruction of nuclein -holding material, comes normally in large part from the leucocytes and is therefore increased in leucocytoses.

Although the uric acid per 34 hours was determined on 23 different days, and on four of these the urea and total nitrogen also, on no occasion did the total uric acid excretion, or the relation between the nitrogen of the uric acid to that of the urea or to the total nitrogen exceed the normal limits, showing that the views of Horbaczewski are not universally correct. In this case, however, the leucocytosis differed somewhat from the ordinary in that here the eosinophiles were the cells markedly increased ; in his cases the ordinary polymorphonuclear neutrophiles.

(c) The mus'ie. The changes in the muscle were extensive. There was a great proliferation of the muscle nuclei throughout the section ; about the fibres containing trichina? this proliferation was very marked, especially in the second specimen ; not so extensive in the earlier specimen. In fact, in a few places where the parasite had but just wandered into the primitive bundle no change in the muscle substance nor any proliferation of nuclei was visible. Most of the fibres containing the worm showed a conversion of the muscle substance into a finely granular faintly-staining material containing many large swollen nuclei, i. e. the proliferated muscle nuclei ; and about many of the proliferated nuclei, both in the more and in the less degenerated portions, distinct vacuoles could be made out.

Throughout the specimens the muscle showed various forms of disintegration, in some places a longitudinal splitting of the fibres into fibrillaj, in other places the formation of what might be called muscle cells, the muscle nucleus taking about itself some of the muscle substance and separating itself from the fibre; while in still other places a peculiar transverse splitting up of the muscle into disks, the nuclei here proliferating transversely instead of in the usual longitudinal method, was noted.

Besides these changes there were seen in the first specimen many polymorphonuclear cells, some showing a finely granular protoplasm which did not stain to any extent with acid stains (the so-called neutrophiles), some distinct eosinophiles with large deeply-staining granules, and beside these, cells which somewhat suggest transitional forms, showing in the protoplasm of the cell body fine granules, but with a distinct affinity for the acid stain ; and all these cells seemed to be acting as phagocytes in the disintegrating muscle, being often seen in little lakes or bays in the degenerating bits.

In the second specimen there were decidedly fewer neutro


philes and many more eosinophiles tlian in the first. That in

both cases these were typical eosinophiles was shown by staining them in the different acid stains and in the Biondi-IIeideuhein triple stain.

At the same time with this greatly increased projiortiou of eosinophiles in the extra-vascular leucocytes in the muscle, Ihe Mood vessels in the inferfascicuhir connective tissue showul the same proportion of neutrophiles and eosinophiles as icas found in the blood count for that day.

In another specimen of muscle from a case of acute trichinosis which was obtained from the pathological museum, great (juantities of eosinophiles were also found.

The study of the blood, showing the steady increase of the eosinophiles at the expense of the neutrophiles, together with the identical character of the nuclei of the two forms, would tend to support the view held by some observers, that the former variety of cells is derived by some transitional change from the latter.

That such a change might take place in the muscle is suggested by the presence here of neutrophiles, eosinophiles, and what may be regarded as transitional forms, in large quantities. Particularly suggestive is the great disproportion between neutrophiles and eosinophiles seen in the second muscle specimen. Here the eosinophiles were much increased, the neutrophiles correspondingly decreased, while the blood-vessels in the interfascicular connective tissue showed but the same proportion of these forms as was to be made out in the specimens of the peripheral blood for the same days. It is further noteworthy that the eosinojihiles increased in number soon after the increase in severity of the muscle symptoms, and shortly after the decrease of those symptoms, diminished gradually, descending toward the normal point as the symptoms abated. Suggestive also is the presence of large numbers of eosinophiles in a specimen of muscle from another case of acute trichinosis.

Dr. OsLBR. — This is the only case of trichinosis which has been in the hospital, or it is safer to say the only case recognized, since we know that not infrequently the disease escapes recognition or is mistaken for some other disorder. This is the second case which I have seen clinically, while in the postmortem room I have found on eight or ten occasions the calcified cysts. Mr. Brown is to be congratulated on the very thorough way in which he has followed this case.

Dr. Thayer. — The evidence offered by Mr. Brown in favor of the origin of the eosinophilic cells by transition from the so-called neutrophiles is very suggestive. The total number of polymorphonuclear cells found in the circulating blood was practically what one would expect in a leucocytosis of that extent. And yet, examining this percentage which normally should consist almost absolutely of so-called neutrophilic leucocytes, we find the great majority represented by eosinophiles. The fact also that in the affected parts the bloodvessels contained the same relative proportion of eosinophiles and neutrophiles as did the peripheral vessels, while the tissues round about contained an enormously greater percentage of eosinophiles, is very interesting.

That the so-called neutrophilic granules stain often with acid coloring matters is well known. With good acid dyes


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these granules almost always take a slight stain, and by sonie obseryei'S botli eosiuophiles and neutropbiles are classed as acidophilic cells. They stain, however, much better in fluids consisting of a mixture of acid and basic coloring matters. As Mr. Brown has sharply pointed out, this acid staining of the smaller granules was uot to be made out at all in the specimens of blood and in the blood-vessels in the tissues, and the fact that outside of the vessels in the affected parts numerous apparent transitional forms between the non-granular polymorphonuclear wandering cells and the true eosinophiles existed is very suggestive. That these cells were true eosiuophiles in the sense of Ehrlich, Mr. Brown has proven by careful tests with a number of different acid coloring matters.

The idea that the eosiuophiles represent a further change in the cell which we know as the neutrophile is, as Mr. Brown has said, not a uew one, but I am not aware that any argument in favor of this view as forcible as that which he presents has yet been published.

With regard to the actual blood condition — the increase of the eosinophiles — no similar case exists in the literature; the percentage of eosiuophiles in this instance is moi"e than twice as large as has been reported in any other case.

Dr. Barker. — Mr. Brown has referred, in speaking of the degeneration of the muscle, to a splitting up' of the muscle fibre into transverse disks. I should like to ask him whether or not he has been able to make out just where the splitting


occurred. Though several histologists have emphasized the fact, it does uot appear to be generally kuown that the splitting iu the muscle fibre may occur with some reagents at one level, with other reagents at an entirely different level. Thus in the formation of the so-called Bowman's disks through the action of alcohol, the two layers Q (doubly refractive substance of Briicke) with the layer M (Hensen's line) in between are always present in the disk. On the other hand, ou treatment of muscle with certain acids (acetic, picric or hydrochloric), the splitting occurs between the two layers Q, each disk having then in its middle the layer Z (Krause's transverse line or membrane). It would be interesting to know, for the degeneration described, whether the splitting occurred at either of these two levels or at still another level.

I gather from his paper that Mr. Browu favors the view that the eosinophile granules represent the cyto-mikrosomas of the cells in which they occui\ This view, recently si;pported by Lovell Gulland, was previously urged by Martin Heidenhain, who found that the eosinojjhile granules stain black with his iron-haamatoxylin staining method, and that it is often possible to make out an arrangement of the granules radial to the attraction sphere of the cell. Both these observations are in favor of the cyto-mikrosomal nature of the granules.

The occurrence of such an enormous number of eosinophiles in the circulating blood is truly remarkable and makes the case unique in the bibliography.


PROCEEDINGS OF SOCIETIES,


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of December 7, 1896.

Dr. Thayer in the Chair.

On Certain Visceral Pathological Alterations, the Result of Superficial Burns.— Mr. Bardebn.

Extensive superficial burus are followed by severe constitutional symptoms. The great pain felt at first is followed by a benumbing of the senses and by sleepiness. At times there may be delirium and cramps. The pulse becomes weak, the respiration shallow and irregular. The temperature, after a short rise, falls below the normal. There may be vomiting and diarrhcea, and haamoglobin may appear in the urine. Death within 48 hours usually follows a burn which has involved two-thirds of the surface of the body. The burn need not be of an extreme grade. Death has often followed burns so superficial as to give rise merely to an erythema.

It is clear from this latter class of cases, at least, that alterations in the internal organs may follow the burning of the skin which cannot be accounted for on the supposition that they are directly caused by the heat. Thus arises the question as to the nature of the physiological relations between the lesions produced in the skin and the resulting constitutional effects. Many hypotheses have been advanced to answer this question, some of which have been supported and others destroyed by experimental work on animals.

Many of these hypotheses have been based upon the con


ception of a loss of normal cutaneous activity. But experiment has shown quite conclusively that death after burns is to be ascribed neither to the retention in the blood of products normally excreted through the skin, nor to heat radiation due to paralyzed blood-vessels in the latter structure.

Again death has been referred to changes produced in the blood itself directly acted upon by the high temperature. It is known that erythrocytes are destroyed by a comparatively low temperature (55° 0.). This has led to the supposition that the general pathological effects are due to loss of functional red blood corpuscles, or to irritation produced in the kidneys and other internal organs by the products of their disintegration. But a more generally accepted view is that the blood is so altered by the elevation of temperature as to give rise to extensive thrombosis, death resulting from the disturbances of circulation.

Another view has been advanced more recently. Kijanitzen, who extracted from the blood of dogs experimentally burned, substances similar to Brieger's ptomains, and Eeiss, who found toxic substances in the urine of persons accidentally burned, believe that they have brought forward evidence in support of the idea that the blood in severely burned animals is rendered toxic.

During the past year five small children were brought to the Johns Hopkins Hospital so severely burned that death in each case followed within a very few hours of the accident. At the suggestion of Dr. Flexner I took this opportunity of studying


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the histological alterations found in the tissues of the body after burns. A careful autopsy was made in each case by Dr. Flexner, and parts of the various organs were preserved and prepared for microscopic examination.

The lesions in all five cases were strikingly similar. Of the gross lesions the most notable were cloudy swelling of the liver and kidney, acute swelling of the spleen, and swelling and congestion of the lymphatic glands and other lymphatic tissue.

Microscopically, the most interesting lesions noted were parenchymatous degeneration of the kidneys and liver, focal areas of necrosis in the liver, and pronounced focal necrosis in the lymphatic tissue.

The lymphatic tissue was affected throughout the body. The Malpighian corpuscles of the spleen, the tonsils, gastric lymphatic follicles, enteric solitary and agminated follicles and the lymphatic glands all showed essentially the same changes.

The lymphatic glands were much swollen and at times congested. The earliest changes were in the follicles and consisted of an ojdematous swelling. This was more marked towards the centre of the follicle, in an area corresponding to the germinal centre. In areas of less advanced alteration the lymphocytes were merely less closely packed together than is usual. But in the areas of more marked change, the lymphocytes were swollen and their nuclei fragmented. In these cases the follicle presented a remarkable appearance. It was not only greatly swollen, but at the edges a rim of closely packed lymphocytes existed, while at the centre swollen and distorted lymph cells, bits of protoplasm and fragments of nuclei were seen scattered about, some lying free, others enclosed in large flat endothelioid cells.

The lymph cords as well as the follicles were swollen, while the lymph sinuses seemed less distinctly marked off than usual from the reticulum in which the lymphocytes of the cords lie imbedded. Here and there throughout the gland groups of degenerating cells might be seen, but the areas of distinct focal degeneration were confined as described above, to the follicles.

Calvert has shown that the terminal artery breaks up in the centre of the follicle into capillaries which radiate towards the periphery of the follicle. It seems possible that the lesions focalized just at this region may in some way hold special relation to the circulation of tlie blood. For if the blood in these cases contains toxic materials, it is conceivable that it is just at the centre of the follicle that the poisonous plasma acts with greatest intensity on the lymph cells.

In the lymphatic follicles of the tonsils and stomach and in the Malpighian bodies of the spleen focal degeneration essentially similar to that of the follicles of the lymphatic glands occurs. In the intestines the greatly swollen lymphatic follicles, solitary and agminated, showed extensive focal areas of degeneration.

In these areas of degeneration in the lymphatic tissue we find appearances essentially similar to those seen after the injection into the body of various bacterial and other toxalbuminous substances. Indeed, the lymphatic glands from our cases of skin-burn might readily be mistaken for the lymphatic glands of children dead of diphtheria. The


lesions in the other organs are also essentially similar to those found in the bodies of persons dead from the acute infectious diseases. It seems, therefore, justifiable to consider that one of the main causes of death after burns is to be sought in a toxaemia caused by alterations in the blood and tissues, the direct effect of the elevation of temperature; a view which is further strengthened by the clinical evidences and the experimental work of Kijanitzen and others.


NOTES ON NEW BOOKS.

The American Year-Book of Medicine and Surgery : being a yearly digest of scientific progress and authoritative opinion in all branches of medicine and surgery, drawn from journals, monographs and text-books of the leading American and foreign authors and investigators. Collected and arranged, with critical editorial comments, by J. M. Baldy, M, D., and twenty-six other physicians, under the general editorial charge of George M. Gould, M. D. [Philadelphia, 1897 : W. B. Saunders, 925 Walnut Street.)

This year-book amply justifies the high expectations which were excited by the excellent character of the similar volume published last year. It is an encyclopedic collection of new medical literature gathered from all lands and every field of medical knowledge. It is not a mere aggregation, but a discriminating digest of the latest knowledge in medicine, with frank opinions and critical comments by painstaking and competent men. The special comments of the editors as distinguished from the authors are enclosed in brackets, to facilitate reference to them.

The completeness of the department of medicine, which has had the editorial supervision of Pepper and Stengel, is shown by the fact that it covers more than 180 pages. Among other interesting matter the sections on the Schott method, typhoid fever, malaria and myxedema are probably of the most interest. In view of the extravagant claims for the different methods of aborting typhoid fever, it is gratifying to notice that the authors ask that all cases treated by these methods be more carefully studied and the symptoms more minutely described.

Under the head of surgery, which occupies 248 pages of the volume, Keen and DaCosta give a valuable resume of the most recent work in ansesthetics, with sensible comments upon the dogmatic assertions of many experimenters. It is refreshing to read the following: " Wunderlich, from a statistical study, concluded that albuminuria was more apt to be induced by chloroform than ether. Beck from a statistical study concluded that albuminuria was most apt to be caused by ether. We are thus confronted by carefully compiled reports which are diametrically opposed and absolutely contradictory. The humble surgeon who venerates statistics too much to use them is lost in uncertainty. We are told that figures cannot lie, and yet only one of these statements can be true. Which is the truth we cannot yet decide, as we know of no birthmark to prove identity."

The operative treatment of perforation in enteric fever would seem to be presented in too gloomy colors, in the light of Finney's recent statistics.

The article on diseases of the gall-bladder is quite full and satisfactory. The same may be said of the careful and conservative article on the use of the x rays.

Obstetrics, under the editorship of Hirst and Borland, occupies about 100 pages, and presents many topics of special interest to the general reader, notably the sections on the pathology of pregnancy, abortion and extra-uterine pregnancy.

The section on gynecology, by Baldy and Borland, occupies upwards of 200 pages, and touches upon a variety of interesting


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matter. The objection presented to Clark's radical operation for the relief of uterine cancer, that but few patients can endure the shock of the prolonged etherization, seems hardly tenable in the light of actual practice. The chapter on nervous and mental diseases, by Church and Patrick, is thoroughly well worked out, and presents a good review of the work of the past year. The section on materia medica is an excellent feature of the book. All things considered, the book is well arranged, admirably edited and well printed. Every physician who does not have leisure to inform himself on the latest advances in medicine and surgery from original sources, should procure and carefully read the volume.

Architecture of the Brain. By Wm. Fuller, M. D., Grand Rapids, Michigan. 1896. Pages 1-183, with many illustrations. In this volume are described and pictured the general gross relations of the brain as seen (1) from the external surface, (2) on dissection, and (3) in a series of frontal sections. The author has had a large experience in dissection of the central nervous system and in the preparation of castings in plaster of the dissections which he has made. No person except one who has busied himself in work of this kind can easily estimate the amount of labor which has preceded the publication of the book.

After a description of the membranes, thecerebro-spinal axis as a whole is described. The cerebrum is then taken up and the method of dissecting it outlined. A discussion of the structure of the cerebellum, of the pons varolii, of the medulla oblongata and spinal cord follows. Throughoutthe book the mainstressis laid upon the gross morphology, but there are brief chapters concerning the nerve tracts of the cerebro-spinal axis and the central origin and relations of the cranial nerves. On pages 130-133 there is a brief discussion of topographical cerebral localization. L. F. B.

Annual Report of the Supervising Surgeon-General of the Marine Hospital Service of the United States for 1893. Vols. I and II. (Washington: Oovernment Printing Office, 1894-1895.) These volumes present a very complete and satisfactory account of the operations of the Marine Hospital Service for 1893. The most valuable papers are a carefully prepared account, by Surgeon Stoner of Baltimore, of the origin and development of this Service, which should be read by all who desire to familiarize themselves with its history, and the " Report of the Commission to Investigate the Cholera Epidemic," prepared by Dr. Walter Kempster and Surgeon Fairfax Irwin, who made an extensive trip in Europe to procure data for it. It is to be regretted that the Commission, while entering into very great detail as to its operations, does not formulate and publish its conclusions in connected form. Scattered throughout the report are many valuable suggestions touching the prevention of infectious diseases and the transmission of contagion, which can only be found by reading many unimportant details. These should have been gathered in an accessible form, so that they might be easily read.

Medical and Surgical Report of the Presbyterian Hospital in the City of New York. Vol. I., January, 1896. By Andrew J. McCosH, M. D., and Walter B. James, M. D. (The Knickerbocker Press, New York.)

This report is the first of a series. It is carefully edited and well illustrated. Many of the papers are carefully written and of great interest to the general profession. The pathological reports are meagre and the protocols published are in most instances brief abstracts. Several of the papers have appeared elsewhere. One of them, that of Dr. Northrop, on Gonorrhoeal Arthritis, is more popular than scientific, and portions of it read as it the author were thinking aloud. The results of thinking rather than mental operations would be preferable. Taken as a whole, the surgical papers seem to be of the greater value. The volume, however, is worthy of the institution from which it issues and the high character of its editors. It is to be hoped that it will have an annual successor.


BOOKS RECEIVED.

Transactions of the American Gynecological Society. Vol. 21. 1890.

8vo. 490 pages. Wm. J. Dornan, Printer, Philadelphia. Prize Essays on Leprosy. By Newman, Ehlers and Impey. 1895.

8vo. 227 pages. New Sydenham Society, London. Practical Notes on Urinary Analysis. By William B. Canfield, A. M., M. D. Second edition. 1896. 12mo. 106 pages. G. S. Davis, Detroit, Mich. A Pictorial Atlas of Skin Diseases and Syphilitic Affections. In photolithochromes from models in the Museum of the Saint-Louis Hospital, Paris. With explanatory woodcuts and text. By E. Besnier, A. Fournier, etc. Edited and annotated by J. J. Pringle, M. B., F.R.C. P. Fol. Parts IV and V. 1896. W.B.Saunders, Philadelphia. Lectures on Pharmacology for Practitioners and Students. By Dr. C. Binz. Translated from the second German edition by Arthur C. Latham, M. A., M. B. Oxon., M. A. Cantab. Vol. 1. 1895. 8vo. 389 pages. The New Sydenham Society, London. Autoscopy of the Larynx and the Trachea. (Direct Examination without Mirror.) By Alfred Kirstein, M. D. Authorized translation (altered, enlarged and revised by the author) by Max Thorner, A. M., M. D. 1897. 12mo. 68 pages. The F. A. Davis Co., Philadelphia. The Practice of Medicine. By James Tyson, M. D. 1896. 8vo.

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84


JOHNS HOPKINS HOSPITAL BULLETIN.


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BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. Vlll.-No. 74.]


BALTIMORE. MAY, 1897.


[Price, 15 Cents.


GO]srT:E3srTS.


PAGE.

The Association between the so-called Perinuclear Basophilic Granules and the Elimination of the Alloxuric Bodies in the Urine. By T. B. Fittcher, M. B., 85

Encysted Dropsy of the Peritoneum secondary to Utero-tubal Tuberculosis and associated with Tubercular Pleurisy, Generalized Tuberculosis and Pyococcal Infection. By ClariBEL Cone, :M. D., 91

A Visit to Bad Nauheim, with the Purpose of Investigating the "Schott Treatment" for Chronic Heart Disease. By C. N. B. Camac, M. D., - - - 101

A Case of Porokeratosis (Mibelli) or Hyperkeratosis Excen


trica (Respighi) with a remarkable Family History. By T.

Caspar Gilchrist, M. B.C. S., L.S. A.,

A Rapid Method of making Permanent Specimens from Frozen

Sections by the Use of Formalin. By Thomas S. Cullen,

M.B., Proceedings of Societies :

Hospital Medical Society,

Typhoid Perforation treated by Surgical Operation [Dr. Finney].

Notes on New Books,

Books Received, - ..


107


108


113 113


THE ASSOCIATION BETWEEN THE SO-CALLED PERINUCLEAR BASOPHILIC GRANULES AND THE ELIMINATION OF THE ALLOXURIC BODIES IN THE URINE.

(From the Medical GUnic of Prof. Eravs in Oraz.) By T. B. Futcher, M. B., Instructor in Medicine, Johns Hopkins University and Asst. Res. Physician, Johns Hopkins Hospital.


In 1894 Neusser described a peculiar granulation in the leucocytes of patients suffering from a uratic diathesis. This term was given a wide meaning, and under it he included gout, uratic lithiasis, as well as the various forms of "irregular gout," as muscular rheumatism, nervous asthma, skin affections, gastro-intestinal derangements, diabetes, leuksemia, neuralgia aud neurasthenia. These granules were brought out by staining freshly dried specimens of the blood with a modified Ehrlich's triacid mixture in which the basic ingredient was relatively increased. They are basic staining granules, and with this mixture appear as greenish black or dense black droplets over and about the nuclei of the leucocytes. They vary considerably in size, the smallest being about the size of the neutrophilic granules, and the largest considerably larger than the eosinophilic granules. Often they have a glistening or refractile appearance. They are always in immediate contact with the nucleus, never being present amongst the ordinary granules of the leucocytes. They give one the idea that they constitute some substance which has been squeezed out of the nucleus. Neusser found them most abundant in the mononuclear leucocytes, in which they often form a complete


ring about the nucleus, but stated that they were also present in the polynuelear leucocytes and eosinophiles. He believed that they were of the nature of a nucleo-albumin in composition, and saw in their i^resence a sign for an increased uric acid production in the organism. This assumption was based on the analysis of the urine of 100 patients, in whom, along with the already described blood condition, an elimination of from 0.8 to 1.5 grams of uric acid, and a uric acid coefficient within the limits of 1 : 30 to 1 : 20 (1 : 50 being normal) were found. It is important to note that the patients on whom these observations were made were not brought under a condition of nitrogenous equilibrium.

The clinical interest of these basojihilic granules would be very great if it could be proven that in an extended series of cases they were associated only with a uric acid diathesis and were entirely absent in other affections. If such could be proven we would then have a ready clinical means of differentiating symptoms due to a uratic diathesis from those arising from some other cause. Neusser himself states that they are also to be found in a certain percentage of cases of tuberculosis, and believes them to be of prognostic value. He claims to have


86



found that cases showing the granules run a more favorable course, and that the lung infiltration is more likely to undergo fibroid change than in cases where the granules are absent.

Kolisch, a pujiil of Neusser's, has advanced the theory that a uric acid diathesis is not due to an anomaly of in the formation of or in the relative solubility of uric acid, but in the increased production of the alloxuric bodies (uric acid -|- xanthin bases), out of the products of nuclein destruction. He found that in cases where the perinuclear granules were abundant that there was a definite increase in the quantity of alloxuric bodies eliminated. The increase was due to a marked increase of the xanthin bases, the uric acid being relatively diminished ; and it was to the presence of these bases circulating in the blood that the symptoms of a uratic diathesis were due, and not to any anomaly in the formation or excretion of uric acid. Neusser and Kolisch, although they both believe that the basophilic granules bear an intimate association with the causation of the uratic diathesis, differ in their views as to which ingredient of the urine is increased by their presence. Neusser found an increased elimination of uric acid, while Kolisch found that the uric acid was relatively diminished, and the xanthin bases markedly increased, resulting in a total increase in the amount of the alloxuric bodies eliminated.

With the exception of the above difference, Neusser and Kolisch agree that the occurrence of the perinuclear basophilic granules indicates an increase in the nuclein constituents of the blood. Direct analyses of the blood for the amount of nuclein contained in it were naturally not made; and pure color reactions, even from a qualitative standpoint, are unreliable, as shown by L. Heine. If one accept without further questioning Neusser's view that the perinuclear granulation is a morfihological criterium for an over-production of nuclein derivatives from the cell nuclei, it is not easily explainable why an increase in the quantity of the alloxuric bodies eliminated in the urine should follow. If one considers these granules identical with the pyrenogenic granules of Lowit found in the leucocytes of the river crab (in the arthropoda the uric acid is not formed from the nuclein materials) and in certain normal leucocytes of the bone-marrow, then they fall under the general heading of karyorhexis or breaking up of the nucleus, and would more likely indicate a chromatolytic degeneration of the leucocytes. Prof. Kraus was able to demonstrate similar granules in the liver cells when portions of the liver substance were removed from the body while still warm and kept in a moist chamber at 40° C. At a definite stage in the breaking down of the nuclei he found granules in the protoplasm of the liver cells resembling and staining similarly to those found in the leucocytes by Neusser. If such a condition takes place under any circumstances, either physiological or pathological, in the living person, an increase in the alloxuric bodies eliminated might be expected.

In studying the subject of Neusser's granules I have endeavored to determine whether there is any regular coincidence between the presence of these granules and the elimination of the alloxuric bodies, and further, whether the granules are found only in cases showing the symptoms of a uratic diathesis.

Doubt as to this intimate association arose in my own mind while examining the blood of patients for the basophilic


granules, at first without studying their effect on metabolism. In a very large number of cases examined, both in healthy and diseased persons, I have never failed to find the granules present. Four of these cases were cases of true gout with typical joint affections and well defined tophi in the ears. In two of these cases the granules were very abundant, but not more so in the mononuclear than in the polymorphonuclear leucocytes. In the remaining two cases they were on the whole not very abundant, and the polymorphonuclears showed the granules more numerous than did the mononuclears. Further, I was able to convince myself, both in Baltimore and in Graz, that the granules were not more marked in the blood of patients suffering from the so-called uratic diathesis than in other diseases, or even in certain apparently healthy individuals. The fact that the granules are found in other diseases than in uratic diathesis, and also in healthy persons, lessens their clinical interest. Neusser believed their presence in tuberculosis was a favorable sign. In this disease I have observed cases with abundant granules and others with few granules without noticing any difference in its subsequent course. The granules vary in richness in the leucocytes from day to day in the same individual, notwithstanding his living under the same conditions of nourishment, etc. This fact seems to diminish the significance of the granules. It seems more common for variations of this kind to occur than for the granules to remain constant from day to day. No method seemed practicable for making an accurate count of these granules, and in the following cases reported it seemed sufficient for all practical purjioses to stain the specimens of dried blood and to compare from day to day the amount of granulation present in the different forms of leucocytes.

The following cases, in which the basophilic granules and their effect on metabolism were studied, were undertaken especially to ascertain whether the amount of granulation present really influenced the quantity of the alloxuric bodies eliminated in the urine.

In all, 8 cases were carefully studied. Blood specimens were stained each day with Neusser's staining mixture, and the same technique followed from day to day. The patients were as nearly as possible brought under the conditions of nitrogenous equilibrium before the observations on the urine were concluded. Each case was followed for a period of 5 to 6 days, and during this time the same amount of food was taken each day, and the body weight from day to da\' remained practically constant. The total amount of nitrogen ingested in the food and eliminated in the urine and fteces was estimated daily. In all the cases the alloxuric bodies were estimated, and in two cases the uric acid as well. The nitrogen was detei-mined according to the method of Kjeldahl, the uric acid according to Ludwig's, and the alloxuric bodies according to the Kriiger-Wulf* methods.

In order to assist in the understanding of the following tables I give what is considered the normal amount of nitrogen in grams contained in the alloxuric bodies for the 24 hours, as found by various observers who have made determinations up to the present date.


•Zeit. flir physiol. Chemie, Bd. XX.


May, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


87


For the 24 hours :

Kolisch gives 0.260 gram.

Weiutraud (1) 0.344-0.360

(2) 0.433-0.534 Richter 0.380

Magnus-Levy 0.506

Richter 0.387

I myself found in healthy persons (1) 0.499

(2) 0.551

Judging from these analyses it may be considered that values above 0.4 gram are physiologically high, while those above 0.5 gram may be regarded as pathological.

Case 1. — Dr. K., aged 32 years, weight 79.5 kilograms, with a well-marked tendency to a gradually increasing corpulence. Not inclined to undertake great muscular exertion, but in every respect perfectly healthy. After nitrogenous equilibrium had been established, 1.5 liters of Carlsbad water (Miihlbrunn) were drank daily for a period of 8 days.

The daily diet was as follows: Ham, 150 grams; roast beef, 100 grams ; milk, 500 grams ; 6 breakfast rolls ; butter, 65 grams; rice, 60 grams; sugar, 3 pieces; black coffee (infusion), 100 grams ; sherry, 100 grams ; soda water, 2 bottles.

The above diet represented about 1968 calories (about 25 calories per kilogram body weight), which were made up as follows :


Albumin Pat

Carbohydrates Alcohol


Total


362.17 calories. 837.73 646.35 122.15

1968.40


Table 1. — The Urine.


Date.


Q



a

U ID


at

'"C in


if



July 6 " 7 " 8 " 9 " 10 " 11 " 12 " 13* " 14 " 15 " 16 " 17 " 18 " 19 " 20


1

3 4

5 () 7 8 (1

10 11 12 13 14 15


995 1240 1630 1200 1080 1160 1630 2270

2«no

2345 27C0 3120 3045 2920 2810


14.7638 12.8898 14.7759 14.0700 15.5547 15.0666 15.4947 15.7682 14.1159 15.3560 13.9482 15.5719 12.9062 14.9825 14.. 3732


0.6042 0.4.318 0.5262 0.4169 0.4430 0.5602 0.5058 0.4149 0.4459 0.4042 0.3780 0.3849 0.3810 0.3244 0.4025


0.2550 0.2613


4.16 3.35 3.56 2.97 2.84 3.71 3.26 2.63 3.16 2.63 2.71 2.47 2.95 2.16 2.80


From 13 to 20 Carlsbad water was drunk. 


Table II. — Nitrogen Balance (N in Grams).


Date.


0% P


41


£ Si


NITROGEN ELIMINATED.


i ,

a — "3 |a|


S


Brlue.


FcBoes.


a


July 10 " 11 " 12

" 19 " 20


5 6

7 14 15


79.300 79.800 79.900 79.050 79.050


16. 2347 15.9769

18.6598


15.5547 15.0666 15.4947 14.9825 14.3732


1.1832 1.1832

'3.3325


16!2498 16 6779

17! 7057


— o'.7oio

+b'.954i


Condition of the leucocytes with reference to Neusser's granules : During the jjeriod in which no Carlsbad water was taken the granules were present only in very moderate numbers. On the other hand, from July 16th to 20th, during which the water was drank, there was a very distinct increase in the number of granules present in all the forms, particularly in the mononuclear leucocytes. At the same time it will be seen that there was a marked diminution in the allo.xuric bodies as represented by the amount of nitrogen eliminated.

Observation II. — Dr. L., a perfectly healthy man, aged 25 and weighing 69.5 kilograms. Muscular, moderate panniculus adiposus, and of a quiet disposition. My colleague, after bringing himself to a point of equal daily nitrogen elimination, drank Carlsbad water for a period of 4 days (1.5 liter of Muhlbruun per day).

The daily diet was as follows : Ham, 250 grams ; veal, 250 grams; milk, 100 grams; wine, 500 grams; tea (black infusion), 250 grams; rum, 15 grams; butter, 50 grams; breakfast rolls, 3.

The above food represented about 1895 calories daily (27 calories per kilo body weight), which were made up as follows:


Albumin Fat

Carbohydrates Alcohol


511.73 calories. 785.49 341.69 256.88


Total


1895.79


Table III.— Urine.


Q


0^


Dally amount of urine In com.


S Ml if


- u a

|g|i


A,


Percentage of alloxurlc body— N of total nitrogen.


June 12


1


1430


25.2421


0.5710



2.27


" 13


9


1815


30.1310


0.5595



1.85


" 14


3


1800


28.1925


0.5237



1.85


" 15


4


1880


30.3996


0.5791



1.90


" 16


5


2000


30.0650


0.5217


0.4222


1.73


" 17*


6


1890


27.2868


0.6515



2.38


" 18


7


3110


29.4983


0.5421



1.83


" 19


8


2840


28.40


0.6908


0.4222


2 43


" 20


9


2730


27.30


0.6162



2.10


f From June 17 to 20 Carlsbad water was drunk.

Table IV.— Nitrogen Balance (N in Grams).



1^


38


t

S

NITBOGEN eliminated.



S



Urine.


FsBces.


a

n


June 14 " 15 " 16 " 19 '• 20


3

4 5 8 9


69.700 6".700 69.800 70.200 70.000


31.7345 31..=S645 31.6679 31.5979


36.3996 30 ('650 28.40 29.30


l.'3V42 1.2619


31.3792 36.5702


+0 8536 -|-'l'.5643


Relation of Neusser's granules in the leucocytes: In the period before Carlsbad water was taken, with the amount of the alloxurlc bodies above the normal (and with a large amount of uric acid), the granules were not particularly abundant. In the second half (June 17-20), when the water was taken, the amount of the alloxurlc bodies eliminated was still higher,


88



whereas the granules had become distinctly diminished in nnmber, particularly in the small mononuclears.

Observation III. — A. F., a young woman, 33 years old, and a cook by occupation. She bad a severe anasmia (red corpuscles 1,900,000 per ccm., leucocytes 6800, and hiemoglobin 35 per cent, according to Fleischl's ha^monieter). The temperature was normal during the observation. Pulse averaged 110 per min. Slight dyspnoea even when at rest. Patient was of rather large frame, and the panniculus adiposus was not particularly reduced. No oedema ; urine free from albumin. Had suffered previously from some gastric trouble, but the symptoms had disappeared. From June 35th to July 7th her weight had become reduced from 57 to 53.4 kilograms.

The daily diet was as follows : Ham, 100 grams ; white bread, 100 grams ; milk, 500 grams; wine (white), 350 grams; water, about 1000 grams.

The diet administered represented about 938 calories (17 per kilo body weight), which were made up as follows :


Albumin Fat

Carbohydrates Alcohol


307.46 calories. 319.30 379.49 133.50


Total


938.65


Table V. — Ukinb.


Date.


1


a

h


.a


2

a a 2


a-2


ntage of uric -Nof otal nl









t>


? a


1



g « o « 


Perc alio bod the trog


July 1


1


1300


1022





" 2


9


1400


1010


10.0940


0.4827


4.78


" 3


3


1100


1014


8.8358


4832


5.46


" 4


4


950


1018


8.0964


0.3608


4.44


" 5


ft


1100


1016


9.9715


0.3735


3.72


" 6


6


750


1028


7.7963


0.3793


4.86



Table VI. — Nitkoqen Ingested (in Grams).



Date.


Day of observation.


Ham.


White bread.


Milk.


wine.


Total nitrogen.


July 1

" 3 " 4 " 5 " 6


1 2 3 4 5 6


4.4480 4.4480 4.4480 4.4480 4.4480 4.4480


1.5236 1.5236 1.5236 1.5236 1.5236 1.5236


2.9925 2.9925 2.9225 2.9225 2.9575 2.9575


0.0568 0.0568 0.0.i68 0.0568 0.0568 0.0568


9.0209 9.0209 8.9.509 8.9509 8.9859 8.9859


Table VII. — Nitkogen Balance (N in Grams).



o g


>,SS

1^


ll


NITBOGEN ELIMINATED.


111


g



Drluo.


Fceces.


B


July 1 " 2 " 3 " 4 " 5 " 6


1 2 3 4 5 6


54.200 54.300 54 200 53 9011 53.600 53.200


9.0209 9 0209 8.9509 8.9509 8.9859 8.9859


lb'.6940 8.8358 8.0964 9.9715 7.7963


b;3879 0.3879 0.3879 0.3879 0.3879


10.4819 9.2237 9.4843

10.3.594 8.1842


— l'.46i6 —0.2728 -0.5333 —1.3735 +0.8017


Relation of Neusser's granules in the leucocytes : On the day before the analyses were begun the granules were present in very small numbers in the leucocytes. This was also the


case on July 1st and 3nd, when a relatively high amount of alloxuric bodies was being eliminated. On July 3rd there was an apparent and on the following days a very marked increase in the number of granules, whilst the nitrogen of the alloxuric 1)odies both absolutely and in percentage became diminished. Observation IV. — Patient was a woman 45 years of age. Fourteen years ago she had her first severe attack of articular rheumatism, although she has had milder attacks since 1881. Both hands at present show characteristic deformities. Since 1891 she has had symptoms of some cardiac lesion. In 1895, tricuspid and aortic insufficiency was diagnosed. During the period that the patient was under observation she was comparatively well ; good diuresis and no cedema. Average pulserate, 80 ; respirations, 23. Moderate body exertion was possible without dyspnoea. Cyanosis was quite marked.

The diet was as follows : Ham, 100 grams ; breakfast rolls (4), 308 grams; milk, 500 grams; wine (white), 350 grams; tea (infusion), 500 grams; rum, 30 grams; sugar (6 pieces), 30 grams ; Rohitsch water, 300 grams.

These food materials represented about 1386 calories (36 calories per kilo body weight), which were made up as follows:

Albumin 334.19 calories.

Fat 323.47

Carbohydrates 643.19

Alcohol 185.50


Total 1386.35

Table VIII.— Urine.



i


a ga



,


^


% oo


Date.


°


Eg .


i


d j


§ "^ ffl


¥^i'u










f^


fi°"


% g


|gi


§5?g


Perc

bod tho trof


July 19


1


2400


1012


8.2320


0.3276


3.97


" 20


2


2800


1007


9.6530


0.4459


4.61


" 21


3


2150


1012


9.9706


0.3517


3.52


" 22


4


1400


1014


9.6530


0.3463


3.58


" 23


5


700


1023


9.9356


0.4383


4.41


Table IX. — Nitrogen Ingested (in Grams).



Day of



Date.


observation.


Ham.


July 19


1


5.2052


" 20


2


5.2052


" 21


3


5.2052


" 22


4


5.2052


" 23


5


5.2052


3.3473 2.9837

3.3473 2.9837

3.3473 2.8787

3.3473 2.6950

3.3473 2.9312


0.0785 0.0785 0.0785 0.0785 0.0785


0.1312 0.1312 0.1312 0.1312 0.1312


11.7459 11.7459 11.6409 11.4572 11.6934


Table X. — Nitrogen Balance (N in Grams).


Date.



.1


2

NITBOGEN ELIMINATED.


i .


§


Urine.


Fffices.



July 19 " 20 " 21 " 22 " 23


1 2

3

4 5


47.700 47.400 46.800 45.700 46.000


11.7459 11.7459 11.6400 11.4572 11.6934


8.2320 9.6530 9.9706 9.6530 9.9356


0.9985 0.9985 0.9985 0.9985 0.9985


9.2305 10.6515 10.9691 10.6488 10.9341


+2.5158 +1.0944 +0.6718 +0.80S4 +0.7593


Relation of Neusser's granules in the leucocytes: On the first two days of the observation the granules were comparatively few. On Jiily 21 they were relatively increased, whilst the alloxuric bodies, which had been comparatively high on the 20th, were distinctly diminished in quantity.

Observation Y. — The patient was a brewer, 30 years old, with hypertrophic cirrhosis of the liver. Since 1895 he has had icterus, with tenderness in the region of the liver. The jaundice has had a tendency to disappear and reappear. The faeces at times would be distinctly bile-tinged, and at other times free from biliary coloring matter. Appetite good. At present there is a characteristic enlargement of the liver and spleen, no ascites, and no well marked evidence of collateral circulation. No elevation of temperature. Rather poorly nourished ; weight has varied between 62 and 59 kilograms since April 10. Has a retinitis. Urine is free from albumin.

The daily diet was as follows : Ham, 300 grams ; bread, 700 grams ; wine, 500 grams ; tea (infusion), 500 grams ; mm, 30 grams ; sugar (6 pieces), 30 grams ; soda water, 4 bottles.

These food materials represent about 2806 calories (47 calories per kilo body weight), which were arranged as follows:


Albumin Fat

Carbohydrates Alcohol


516.27 calories. 256.21 1726.10 308.00


Total 2806.58

Table XI. — Urine.








^


Date.


1


i



Is

a 5


s?3i2 i


HS^.^



P^


¥


aui


s 3i

o a




May 15


1


1630


1026


13.2511


0.4773


3.60


" 16


2


1830


10:i3


14.6564


0.4153


2.83


" 17


3


1550


1023


16.2778


0.5089


3.12


" 18


4


nno


1024


17.2238


0.4918


2.85


" 19


5


2040


1024


20.2051


0.4118


2.03


" 20


6


1690


1022


16.4352


0.4771


2.90


Table XII. — Nitrogen Ingested (in Grams).


Date.


Day of observation.


Ham.


Bread.


White wine.


Total nitrogen.


May 15-19 " 20


1-5 6


13.0454 11.3237


7.9398 7.9398


0.2625 0.2625


21.2477 19.5260


Table XIII. — Nitrogen Balance (N in Grams).






NITROGEN ELIMIN

o^





^


§2


ATED.


a — t3


<0


Date.








1^


1?


§1


Urine.


Faeces.


5gi


n


May 15


1


59.200


21.2477


13.2510


2.2526


15.5036


-1-5.7741


" 16


2


58.500


21.2477


14.6564


2.2526


16.9090


-1-4.3387


" 17


3


58.500


21.2477


16.2778


2.2526


18.5304


-f2.7173


" 18


4


58.9(10


21.2477


17.2238


2,2526


19.4764


-hi 7713


" 19


5


59.400


21.2477


20.2051


2.2526


22.4577


-0 7900


" 20


6


60.000


19.52G0


16.4352


2 2o26


18.6878


-t-0.3611


Relation of Neusser's granules in the leucocytes : Several days before the commencement of the chemical analyses the granules were much more numerous than they were during the period of examination. There was no variation observed


during the latter period. Altogether the granules were only moderately numerous, but not more so in the mononuclear than in the other varieties of leucocytes. Some of the mononuclears were without granules. It will be seen that the amount of the alloxuric bodies was relatively high.

Observation VI. — This patient was a man also with hypertrophic cirrhosis of the liver. Since 1893 he had complained of gastric and intestinal symptoms. In 1895 enlargement of the liver and spleen was noticed. Icterus has been persistent, with the exception of one interval when he was free. Weighed 49 kilo when he came to the clinic, but has gained slightly since. The blood examination showed 2,500,000 red corpuscles, 7900 leucocytes, and 55 per cent hajmoglobin (Fleischl).

The daily diet was as follows: Ham, 300 grams; white bread, 450 grams ; milk, 500 grams; wine (red), 300 grams; tea (infusion), 500 grams; rum, 30 grams; sugar (6 pieces), 30 grams : Kohitsch water, 2 bottles.

The above diet represented about 2370 calories (48 per kilo body weight), which were made up as follows :


Albumin Fat

Carbohydrates Alcohol


515.65 calories. 385.02 1161.38 308.00


Total 2370.05

Table XIV. — Urine.



C*


2



g



o


Date.


Q^


g^8


as


-2 2 a a

1 °

|a


Alloxuric

body— N 1 grams.


Percentage alloxurlo body— N the total n trogen.


June 7


1


2500


1015


14.4813


0.6650


4.59


" 8


2


2050


1017


16.3590


0.6188


3.78


" 9


3


3200


1013


15.5680


0.7056


4.53


" 10


4


4000


1011


16.2400


0.5425


3.34


" 11


5


2500


1014


15.8375


0.7131


4.50



Table XV. — Nitrogen Ingested (in Grams).*



Date.


Day ot observation.


5am.


Bread.


Milk.


Red wine.


Total nitrogen.


June7A8 " 9&lfi " 11


1 &2 3<s4 5


12.2257 12.2257 12.2257


6.3503 6.3503 6.3503


2.8525 2.8175 2.6162


0.1225 0.1225 0.1225


21.5510 21.5160 21.3147


^Tea, rum and sugar not analyzed.

Table XVI. — Nitrogen Balance (in Grams).




1^


S

NITBOQEN eliminated.



g



Drlne.


Faeces.



June 7 " 8 " 9 " 10 " 11


1

2 3 4 5


49.500 49.400 49.200 50.000 49.600


21.5510 21.5510 21.5160 21.5160 21.3147


14.4812 16.3590 15.5681) 16.2-100 15.8375


1.6595 1.6-95 1.6595 1.659.i 1.659.-,


16. 14071-1-5.4 103 IS !)l85l-f-3 5325 17 227^1-1-4.2885 17.8995-|-V61(i5 17.49704-3.8177


Relation of the Neusser's granules in the leucocytes: Altoo-ether the granules were very few in all the different forms. Most of the white corpuscles are entirely free from the granules, and many almost entirely free. During the period that


90



the patient was under observation there was no apparent variation in the richness of the grannies. On the other hand, the alloxuric body nitrogen was both absolutely and relatively high (0.67, 0.71 gram per day).

Observation VII.— A. man, 20 years old, with physical signs of a commencing left-sided pulmonary tuberculosis. No tubercle bacilli were found in the sputum, however, after repeated examinations. His weight on May 26th was 57 kilo ; he was fairly well nourished. During the period of observation he was free from fever. Leucocytes were 10,000 per cmm. ; hemoglobin 70 per cent (Fleischl).

The daily diet was as follows: Ham, 300 grams,; white bread, 450 grams; milk, 500 grams; wine, 500 grams; tea (infusion), 500 grams; rum, 30 grams; sugar (6 pieces), 30 grams; Eohitsch water, 2 bottles.

The above food represented about 2370 calories (41 per kilo body weight), which were made up as follows:


Albumin Fat

Carbohydrates Alcohol

Total


615.65 calories. 385.02 1161.38 308.00

2370.05




Table XVII.—


Urine.





i


I




a


» O


Date.



§H


uj?


a a « 


S 1 2


S S 1 1 a




>.H







a "


a"



g MM


S o 2

^O M


Perc alio bod

the troj


May 27


1


4200


1010


15.5820


0.6064


3.89


•' 28


2


3450


1012


19.6822


0.5796


2.89


" 29


3


2700


1013


21 3097


0.5953


2.79


" 30


4


3000


1012


18.7950


0.5853


3.11


" 31


5


3400


1014


20.3490


0.5533


2.72


June 1


6


3350


1012


20.2842


0.5803


2.86


Table XVIII.— Nitrogen Ingested (in Grams)


.*


Date.


Day of observatlou.


Ham.


Bread.


Hllk.


wine.


Total nitrogen.


May 27 & 28 " 29 " 30 Maj 31 & June 1


1 42 3 4 5


15.3515 15.3515 17.4240 17.4240


5.8262 5.8262 5.8262 5.8262


3.9094 2.7956 2.7956 2.9198


0.0350 0.0350 0.0350 0.0350


25.1220 24.0083 26.0808 26.2050


  • Tea, rum and sugar not analyzed.



Table


XIX.— Nitrogen Balance (in Grams).



ig




NITROGEN ELIMIN

itroIm







o« 


Ji,


win










Jat i



O "


S^


»i

TJrlne.


Faeces.


gss « 


May 27


I


57.700


25.1222


15.5820


1.2634


16.8454+8.2763


" 28


2


.'>6.20(i


25.1222


19.6822


1.2634


20.9456+4.1766


" 29


3


55 400


24.0083


21.3097


1.2634


22.5731+1.7352


" 30


4


56.2011


26.0808 1 18.79.50


1.2634


20.0584+5.9214


" 31


5


56.2(0


26.2050 j 21.1.3490


1.2634


21.6124+4.5826


June 1



50.200


26.2050 i 20.2842

1


1.2634


21.5476+4.5574


Eelation of Neusser's granules in the leucocytes : The granules are altogether extremely numerous, particularly in the small mononuclears. There was no appreciable variation in the granules from day to day. In this case, with the large


number of granules, there was found to be an elimination of a large quantity of alloxuric body nitrogen.

Observation VIII. — The patient was a woman 45 years of age, with cirrhosis of the liver. Since 1895 she had complained of gastric symptoms ; pain in the epigastrium. Had emaciated considerably. Had been jaundiced. Thegastric juice showed a very marked acidity ; free and combined HCl 0.35 to 0.41 per cent, and free HCl alone 0.22 to 0.28 per cent. The liver was enlarged, hard and nodular. Spleen was not much enlarged, but was hard and could be palpated at the costal margin. Body weight averaged about 60 kilos. Vomiting was frequent and patient was moderately ansemic.

The daily diet was as follows : Bread, 300 grams ; milk, 500 ; wine, 500 ; tea (infusion from 6 grams), 250 grams ; rum, 30 grams; sugar (6 pieces), 30 grams; Eohitsch water, i bottle.

These food stuffs yielded about 1752 calories (28 calories per kilo body weight), which were made up as follows:


Albumin Pat

Carbohydrates Alcohol


283.31 calories. 233.43 927.33 308.00


Total 1752.07

Table XX.— Urine.


Date.



3

a 2

.bo



a a o!

Sis


SoSS


Percentage of alloxuric body— N of the total nitrogen.


June 24


1


1350


1023


12.4504


0.4831


3.87


" 25


2


lOOO


1022


10.7800


0.4498


4.17


" 26


3


550


1027


8.1428


0.4591


5.63


" 27


4


850


1025


11.5133


0.5087


4.32


" 28


5


1050


1020


11.0618


5375


4.85


" 29


6


1500


1018


11.1938


0.4594


4.10



Table XXI. — Nitrogen Ingested (in


Grams).*



Date.


Day of observation.


Ham.


Bread.


Milk.


wine.


Total nitrogen.


June 24 " 25 " 26427 "28429


1

2 3&4 546


8.8242 6.3491 48425 4.8425


5.6056 5.6056 5.6056 5.6056


2.7037 2.70J7 2.6C95 2.8875


0.0350 0.0350 0.0350 0.0350


17.1685 14.6934 13.0926 13.3706


  • The variation in the nitrogen in the ham was due to the fact

that the patient could not continue to take the full quantity (220 grams) that she was first given.



Table XXII.—


Nitrogen Balance (in Grams).




Ǥ




NITKOGEN ELIMIN

i . US .





s


as


ATED.


8


' ®*




£ Si




is^


§



a"


S^


a

Urine.


FtBces.


oS2


a


June 24


1


60.700


17.1685


12.4503


1.3508


13.8011


+3.3674


" 25


2


60.400


14.6934


10.7810


1.3508


12.1308


+2.5626


" 26


3


59.600


13.0926


8.1427


1.3508


9 4935


+3.5991


" 27


4


59.900


13.0926


11.5132


1.3508


12.86401+0.2286


" 28


5


59.700


13.3706


11.0617


1.3508


12.41251+0.9580


" 29


6


59.500


13.3706


11.1937


1 .3-^08


12.5445|+0.8261


Eelation of Neusser's granules in the leucocytes: The granules were very numerous, especially in the mononuclears.


Mat, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


91


although there was considerable variation in the granules from day to day. As will be seen from the table there was a large amount of alloxuric body nitrogen eliminated.

These observations that have been made do not in any way confirm the theory that there is a regular coincidence between an abundance of the granules and an increased excretion of the alloxuric bodies, nor do they favor the view that Neusser's granules occur exclusively in patients with an alloxuric diathesis. Cases occur in which, with numerous grannies in the leucocytes, there is a relatively small amount of the alloxuric bodies eliminated in the urine, while on the other hand the granules may be almost entirely absent and the alloxuric bodies be excreted in increased amount. Such directly opposed conditions may occur in different individuals having the same


disease, as in the two cases of hypertrophic cirrhosis of the liver. Not infrequently the granules become increased or diminished in the same person without there being a corresponding increase or diminution in the excretion of the alloxuric bodies. In fact, increase in the number of granules may be accompanied by a diminution of the alloxuric bodies and vice versa.

From the information obtained by the study of the above cases one seems justified in concluding thattlie supposed relationship between the perinuclear basophilic granules and an alloxuric diathesis, as claimed by Kolisch, is purely empirical.

In conclusion, I must thank Professor Kraus and his assistants for many kindnesses and for valuable aid in carrying on the above analyses.


ENCYSTED DROPSY OF THE PERITONEUM SECONDARY TO UTERO-TUBAL TUBERCULOSIS AND

ASSOCIATED WITH TUBERCULAR PLEURISY, GENERALIZED TUBERCULOSIS

AND PYOCOCCAL INFECTION.

By Claribel Cone, M. D., Professor of Puthology, Woman's Medical College, Baltimore. [From the Pathological Laboratory of the Johns Hopkins University and Hospital]


The following case is of interest not so much because of lesions in themselves unique, as because of the rare combination of many lesions, the extensive character of these lesions, and the multiple nature of the infection.

The case has many features in common with that reported by Gardner,' of Montreal, in the year 1885, and is similar to those described by Wm. T. Howard,' of Baltimore, the same year.

Clinical History.

N. A., primipara, aged 30 years ; colored. Admitted to the Maternite of the Hospital of the Good Samaritan, in the service of Dr. B. B. Browne, November 19, 1894.

The patient had been married several years ; had no children, no miscarriages. Menstruation commenced at the age of 15 ; it had always been regular, painful and profuse, lasting from six to eight days, during which time she was compelled to remain in bed. Her last jieriod occurred about the middle of March, 1894.

Past History. No family history could be obtained. The patient had measles after reaching adult life. Five years ago she suffered with an attack of " malaria " which lasted three months ; at this time she claims to have been " very sick." The attack recurred in September, 1894.

History of Present Condition. The patient is in the eighth month of her pregnancy. Throughout this time she has been feeling ill ; she has had pain in the back and abdomen, increased on exertion. At present there are constant backache, and pain in the lower part of the abdomen. Appetite is good ; bowels constipated ; urine of low specific gravity, otherwise normal.

E.t'xmination. Fcetus occupies the left occipito-posterior position. In the right iliac region is a mass, partly soft, partly resistant, which seems to be connected with the uterus, and is not painful except on deep pressure.


On November 18 at 9.30 p. m. the woman was delivered of a healthy child, but owing to uterine inertia the placenta had to be removed. The labor was protracted, lasting 38 hours. The perineum was lacerated and repaired at once. Two days after delivery the patient was attacked with a chill followed by fever and sweating. The record of the puerperium shows an irregular temperature of septic character whose highest point was 104.3°, whose average was 103°. There was no fever after the second week and the patient's condition was recorded as good.

On January 19, 1895, she was discharged from the hospital apparently in fair health. The following April the patient visited the hospital clinic for treatment, considering herself again pregnant since February. In July, 1895, she returned with enlarged abdomen and general discomfort. At this time she claimed to have felt the foetal movements; in August she was seen at the clinic by Dr. B. B. Browne, who, after examination, did not think her pregnant.

Second Admission. In October, still believing herself pregnant, the woman was readmitted to the Maternite. After careful examination under an anaesthetic, pregnancy was definitely excluded from the diagnosis. At this time a large hard mass was found to the right of the uterus and apparently connected with it. The nature of the tumor could not be determined. Following the ether examination the woman became quite ill. There was great pain in the lower part of the abdomen and sudden rise of temperature. The patient was then transferred to the gynecological department of the Hospital of the Good Samaritan. After the second day the abdomen beo-an gradually to swell, and on December 1st it was much distended. The patient was losing flesh and strength. The temperature showed a typical hectic range, being normal or subnormal in the morning, with an afternoon rise fluctuating between 100° and 103°. The lowest point reached was 95.4°, the highest point 104°.


92



Repeated examinatious of the sijutum showed no tubercle bacilli.

Diagnosis. Encysted dropsy of the peritoneum, probably tubercular.

Operation. For removal of the dropsical fluid. On February 26 th a laparotomy was performed by Dr. Browne. Au incision 5 cm. long was made in the median line of the abdomen. From this opening about eight litres of transparent, pale greenish fluid escaped. The entire anterior portion of the peritoneal cavity was found to be converted into a suppurating cyst. An additional litre of semi-solid caseous material resembling masses of congealed fat was removed by the hand of the oj)erator from the lower part of the sac where it covered the pelvic viscera on the right side. After evacuation of the fluid the surface of the peritoneum was found thickened and converted into a necrotic membrane resembling the caseous masses which floated in the jius.

Examination of Fresh Abdominal Fluid. The macroscopic appearance was that of a turbid, pale greenish yellow fluid in which floated shreds and flakes of caseous material. On standing it separated into two layers, au upper transparent, greenish fluid and a lower dense, creamy mass. The microscopic examination of this fluid showed numerous pvis cells, some red blood corpuscles and shreds of necrotic tissue entangling pus cells. Staiued cover-sliji preparations of the fluid exhibited numerous cocci in jjairs, clusters and short chains, but no tubercle bacilli were found.

Immediately following the operation the patient's condition was much depressed. She rallied, however, resi^ondiug to stimulation. Her general condition improved and she became much more comfortable until the tenth day, when without pain or other distressing symptom she died suddenly, March 6, 1896. The autopsy was made three hours after death.

Anatomical Diagnosis. Tuberculosis of the Fallopian tubes, uterus, ovaries, peritoneum, pleura, and viscera generally. Acute flbrino-puruleut and caseous peritonitis; acute serofibrinous and hemorrhagic pleurisy ; mixed tubercular, staphylococcus and streptococcus infection ; congestion of viscera; general arterio-sclerosis.

The body is much emaciated. In the median line of the abdomen is a gaping incision. It begins 3.7 cm. below the umbilicus and extends 5 cm. downward, exposing a sloughing, puriform cavity from which bubbles of gas are evolved ou pressure. The subcutaneous fat is quite absent; the muscles are brownish red in color.

Abdomen. On opening the abdomen the entire anterior portion of the peritoneal cavity is found to be converted into a suppurating cyst. This extends from the liver above to the pelvis below, and traverses the lateral diameter of the abdomen from flank to flank, dipping deeply on both sides. The walls of the sac are made up of dense, opaqire, yellow necrotic material about 5 cm. in thickness. The cavity contains a small amount of the same puriform material found at operation. Extending across the cavity obliquely downward, and from before backward, as if to support its somewhat flaccid walls, are four or five dense fibrous bands covered by caseous material, continuous with that lining the general suppurating sac. Of these the largest is in the median line. It is long and almost


cylindrical, measuring 3.7x2.5 cm. in diameter. Its anterior and upper attachment is to the abdominal wall 2 cm. below the umbilicus. Its jjosterior attachment below is by a broad expansion upon the posterior wall of the sac where it dips down to cover the pelvic viscera. A second organized band, smaller, but similar in character to the one just described, is found on the left side. A few adhesions are also found in the posterior wall of the sac on the right side. On transverse section these bauds show an organized, pink, fibrous groundwork thickly inlaid with miliary tubercles and limited by a zone of caseous material. The j)osterior wall of the pus sac is found so densely adherent to the intestines and other adjacent viscera that separation is diflicult. No trace of the normal omentum can be found, and the probabilities are that it enters largely into the comjiosition of the suppurating cyst and the traversing fibro-caseous bands.

The coils of intestine are densely matted together by old tilirous bands and by more recent and lighter adhesions, studded everywhere with yellow miliary tubercles, and form a single compact mass filling the greater part of the abdominal cavity. Not only are the intestinal coils adherent to each other, but they are bound to all neighboring viscera. The mesentery is greatly thickened and contracted, and is thickly infiltrated with yellow miliai-y tubercles.

The mesenteric lymph glands are enlarged, indurated and caseous.

Upon separation of the more delicate adhesions between the ui)per coils of intestine, several smaller cysts about the size of a hen's egg are found. They contain clear straw-colored fluid. There is a slight excess of clear fluid in the posterior peritoneal cavity, which appears to have been more recently infected.

Liver. The liver measures 35x17.5x8.7 cm. in its various dimensions. The capsule is much thickened, and strong adhesions unite it firmly to the diaphragm. The left lobe is drawn out into a tongue-like process, which extends completely across the abdomen, covering the spleen on its anterior and left lateral stirfaces. So completely adherent are these two organs that only on section can a line of organized union be made out. The lower surface of the liver is also in contact with the upper wall of the pus sac, with the stomach and with the intestines, to which it is bound by firm adhesions. On breaking up these adhesions and freeing the surface of its caseous membrane, the capsule is found thickly beset with yellow miliary tubercles. The surface is mottled. Ou section the parenchyma shows the characteristic appearance of nutmeg liver. Scattered throughout its substance are numerous tubercles, both grey and caseous. They are mostly submiliary, but larger ones exist.

Spleen. The spleen is considerably enlarged. It is densely bound down by old fibrous adhesions to all neighboring structures. Its anterior and lateral surfaces are almost completely concealed from view by the tongue-like expansion of liver. The capsule is irregularly thickened and contains caseous miliary tubercles. The consistence is much diminished. It tears readily. Ou section it is congested and contains grey and yellow tubercles, miliary, submiliary and conglomerate in form.



Kidneys. The kidneys are slightly enlarged; the capsules are somewhat thickened, but strip off with moderate ease. The surface of the right kidney shows a shallow circular scarlike depression about 12 mm. in diameter,somewhat paler than the surrounding cortex. Under the capsule of this kidney is also seen a solitary caseous tubercle about the size of a split pea. Upon section the kidneys are congested, somewhat increased in consistence, and contain an occasional isolated tubercle of large size. The circular depression seen upon the surface of the right kidney is found to be the base of a dense, pale, pyramidal area which extends quite down through both cortical and boundary zones, and contains in its centre a small cyst.

Ureters. The ureters ai'e normal, except for a slight dilatation of the right ureter in its upper jiortion.

Pancreas. The pancreas is pink and firm. Its capsule is thickly studded with miliary and conglomerate tubercles; none, however, can be seen in its substance.

Stomach. The stomach is adherent to all adjacent structures. Its mucous membrane shows congestion, most marked along the rugas. Some ecchymoses are found at the cardiac end.

Intestines. In some places the felt-like adherent sac wall forms a partial covering to the intestines. Beneath it, as elsewhere, the peritoneal coat is tolerably §mootb, congested, and contains numerous miliary and conglomerate tubercles. The mucous membrane is more or less congested throughout the entire extent. The congestion is most intense upon the valvulas conniventes. There are no tubercular ulcers, but in places tubercles can be seen extending inward from the peritoneal coat. The walls of the large intestine are thin and very deejily congested. The abdominal lymj)h glands are enlarged and caseous.

TJiorax. The sternum aud costal cartilages cannot be readily lifted because of adhesions between the two layers of the pleura on the right side.

Left Pleural Cavity. The left pleural cavity contains about 2.5 litres of blood-stained lluid with flocculi of fibrin. There is one dense organized baud of tissue connecting the two layers of the pleura (about the region of the seventh rib). There are also a few delicate adhesions in the posterior and lower part of the cavity. The apex is firmly adherent to the chest wall. The lung is compressed by the excess of fluid in the pleural cavity. Both layers of the pleura present a coarse reticulated mottling, as though a loose-meshed network of fibrin had been laid upon a dark red hemorrhagic background. Tubercles are also seen.

Upon the parietal pleura, as it covers the sixth rib, are seen two softened caseous tubercles, each about the size of a split pea. Cover-slip preparations made from one of these immediately at autopsy show the presence of tubercle bacilli and micrococci in large numbers.

Left Ln7ig. The left lung is compressed and atelectatic, except the anterior margin of the upper lobe, which contains a little air. Scattered irregularly and sparsely through the lung substance are miliary and conglomerate grey and caseous tubercles. No cavities nor old tubercular foci can be made out.

Right Pleural Cavity. The right pleural cavity is dry.


The lung is bound down throughout its entire extent by easily detached adhesions. At the base and posteriorly the adhesions are pretty firm.

The pleura is covered with a layer of fibrin of irregular thickness, more or less organized at the base of the lung. It contains caseous tubercles.

Right Lung. The right lung is also considerably contracted by the upward pressure from the abdomen and the lateral pressure from the left thorax. The lower lobes are atelectatic and congested. The upper lobe contains a little air and exhibits along its anterior margin a few emphysematous patches. The distribution of tubercles in its substance corresponds with that of the left lung.

The bi'onchial aud mediastinal lymph glands are enlarged and caseous.

Heart. Owing to the excess of fluid in the left ])leural cavity, the heart occupies a position behind the sternum, almost in the median line. The pericardium, the pericardial fluid, the endocardium and heart valves are normal. The aorta contains thickened yellow atheromatous plaques.

Cranial Cavity. There is a slight increase of cerel)i'al fluid. The meninges of both cerebrum and cerebelliun are congested, particularly on the under surface. The pia arachnoid at the base of the cerebellum contains two or tliree yellowisli wliite bodies resembling miliary tubercles.

Cover-slip preparations made from these nodules show no tubercle bacilli.

The pelvic viscera were removed at autopsy aud jjlaced iu formalin, for detailed description later.

Pelvic Viscera. Uterus. The uterus is S.-"> cm. long, 5 cm. broad aud 3.5 cm. iu the antero-posterior diameter. Both the anterior and posterior surfaces are covered by an opaijue, yellowish white, felt-like membrane, varying from 2 to mm. in thickness. This membrane passes directly from the uterine walls to the other pelvic viscera, forming a complete blanket, and constituting the lower part of the large jiu.s sac which occupied the anterior portion of the peritone.il cavity. Projecting from the middle third of the posterior wall is a myomatous nodule about the size of a large walnut, attached to the uterus by a short and broad pedicle, Fig. 1, M. Springing from the fundus of the uterus about 2 cm. anterior to the right cornu is another pedunculated myoma, large, ovoid, and 9.5x7.5x5.5 cm. in diameter, Fig. 1, M. From the left surface of this tumor springs a cylindrical band about :j cm. long and 13 mm. iu diameter, attaching it loosely to the coiled-up mass of intestines behind. This band is of the same general nature as the fibro-caseous bauds which traverse the abdominal cyst. Another band, broad, flattened, and 6 mm. thick, is attached to the right surface of the tumor. This forms part of the general peritoneal sac. On stripping back the dense, felt-like membrane covering these tumors, their surfaces are found studded with tubercular nodules of a yellowish white color, and from one to three mm. in diameter. The snuiller tumor can be easily shelled out of its capsule, owing to a peculiar orange-yellow caseous material separating the two in the regio^n of the pedicle. The myomata, so far as can be seen, do not contain tubercles in their interior. The uterine wall measures 1 cm. in thickness at the fundus. Fig. 1, F. U., 2 cm.


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anteriorly and 1 cm. posteriorly. It is pale pink in color and is studded with sparsely scattered, yellowish, miliary and con glomerate nodules.

The cervix is 2.5 cm. in length. The mucous membrane of the body presents a shaggy, moth-eaten appearance, of yellowish color and friable consistence. The mucous membrane of the cervix, which is much less rough and friable, still presents indications of the normal rugte. The mucosa varies from 2 to 5 mm. in thickness.

Right Appendages. Springing from the right uterine cornu and extending backward and downward, so as to be completely concealed from view by the large myomatous tumor which filled the right inguinal region, is a mass 8 cm.x5.5 cm.x2.5 cm. in size. It presents at first sight the appearance of an enlarged ovary, covered by the general pyogenic membrane, beneath which, as in the uterus and elsewhere, are miliary and conglomerate tubercles studding the surface. Upon section, however, it is seen to consist of the convoluted tube, thickened and necrosed, with its exaggerated coils held together in a stroma of dense organized connective tissue studded with miliary tubercles. Beneath the lower part of this convoluted mass is seen a portion of the ovary, so completely covered by and adherent to the tube as almost to have lost its own identity. Fig. 1, r. Ov. A longitudinal section through this tuboovarian tumor gives transverse, oblique and longitudinal sections of the much distorted tube. They lie like scattered caseous islands with ulcerated centres, in the tubercle-dotted stroma. The walls of the tube are from 3 to 8 mm. thick, and are for the most part uniformly caseous. Here and there is a nodular studding which gives the mucosa an uneven surface; or again a rich infiltration of the other coats with barely agglomerated caseous tubercles is observed. The fimbriated extremity, dilated, and curled outward in trumpet-like expansion, is directly continuous throughout its circumference with the anterior peritoneal sac. Fig. 1, r. F. E. The folds of the fimbriated end are everywhere visible and appear densely thickened and ragged; the extremity itself measures 2.5 cm. in diameter.

Left Appendages. The left tube is exceedingly tortuous, and from the uterine cornu outward gradually increases in size, terminating in a fimbriated extremity 4.5 cm. in diameter. It is 11 cm. long in its contracted state. Fig. 1, F. E. The folds of the fimbria are transformed into a greatly thickened, motheaten membrane, from whose surface project numerous papillary processes varying in size and shape and measuring from 10 to 14 mm. in length. The interior of the tube bears some general resemblance to the necrotic membrane which covers its surface and which represents the walls of the abdominal sac with which both tubes appear to be directly continuous. The convolutions of this tube, while excessive, as are those of the right side, are not embedded in a dense organized stroma, but are held together by tolerably firm adhesions. These, as well as the surface of the tube, exhibit caseous, miliary tubercles. Fig. 1, 1. T. Longitudinal and transverse sections through the tube show extreme necrosis of its walls. They are more extensively ulcerated toward the outer third, where the condition is most advanced. The lumen at this point is increased to 13 mm. iu diameter. The walls of the tube are here from


3 to 5 mm. thick and consist mainly of caseous material with a narrow outer border of organized tissue. This forms a capsule which can be readily stripped away from the central necrotic mass. The thickness of the tube about its middle portion is 2 cm. There is no lumen visible on cross section, but the entire tube seems made up of one dense, yellowish, homogeneous mass.

'J'he left ovary lies behind and beneath the tube, to which it is bound by adhesions similar to those connecting the convolutions of the tube. Fig. 1, 1. Ov. From this it may be detached with moderate ease. It is about normal in size and position. The surface is covered by the same necrotic membrane, and exhibits upon its removal sago-like bodies. On section the structure is smooth, firm, grey and glistening, showing several corpora fibrosa, and one flattened tubercle Just beneath the surface.

t'onnected with thepelvic viscera and binding them together are portions of the peritoneum which went to make up the original sac wall but which were torn away at autopsy. They are of the same general appearance bs, the necrotic membrane covering the viscera. A similar sac, collapsed and dipping down behind and to the left of the cervix uteri, is covered in by the small myoma above described. This represents the remains of an abscess about the size of an orange which ruptured at autopsy, discharging thick, greenish yellow pus.

The Vagina. There are several small, greyish, flattened elevations upon the surface of the mucous membrane, irregular iu size and shape, some round, measuring from 1 to 2 mm. in diameter ; others with irregular edges measuring about 6x3 mm. in diameter. There is also ^ small superficial ulcer in the posterior vaginal wall just below the cervix. It is about the size of a split pea, has sharp irregular edges, but contains no tubercles in its walls. The vagina is otherwise normal.

The bladder is contracted and is apparently normal.

The rediim is partly covered by necrotic membrane, but shows no abnormalities.

Histological ExAiiisATioif. Pelvic Viscera.

Uterus. The surface epithelium has entirely disappeared, and the uterine mucosa shows a granular necrosis throughout the inner fourth of its thickness. Beneath this the normal stroma is invaded by diffuse tubercle tissue with discrete caseating nodules. It is the union of these nodules near the surface of the mucosa which results in the granular necrosis. In the depth of the membrane the uterine glands are preserved, although the epithelium is swollen and invaded by mononuclear and polymorphonuclear cells. They are often dilated, and contain swollen desquamated epithelial cells, polymorphonuclear leucocytes and granular detritus. The diffuse tubercle tissue consists largely of lymphoid and epithelioid cells, with an occasional giant cell. The discrete caseating nodules present the typical structure of caseous tubercles. The giant cells of both stroma and nodule are round, oval or irregular in shape, with a mural or polar arrangement of the nuclei. The epithelioid cells of the diffuse tubercle tissue are usuallyj round or polyhedral, with small vesicular nuclei. Those ofi


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the caseating nodules are irregular and elongated, with oval, bizarre and wavy nuclei, the close packing of which in the periphery of the nodule gives the appearance of a radiating fringe.

The muscular coat is infiltrated throughout its entire thickness with diffuse tubercle tissue and discrete miliary nodules, most of which are caseous. The diffuse infiltration is represented by small cells with solid and vesicular nuclei, arranged in longitudinal strands between the muscle bundles. The caseous nodules lie next to the peritoneal surface, and are irregularly triangular in shape, with bases toward the serosa. Sometimes the bases coalesce and form a continuous scalloped caseous zone. The muscle cells are increased in number, and here and there are myomatous foci which consist of dense aggregations of cells containing elongated club-shaped nuclei.

The blood-vessels of the muscular coat present interesting features; some of them show the typical changes of endarteritis obliterans, with more or less encroachment upon the lumen. But the most characteristic lesion is the tubercular involvement of the vessel walls. This process sometimes begins in the intima and remains limited to this coat, or extends to the media or adventitia. Sometimes it takes origin in the adventitia and perivascular tissues, and spreads inward in like manner through the other coats. It may be diffuse or circumscribed, it may be a cellular proliferation simply, or show all stages of degeneration, from an early nuclear fragmentation and karyolysis, to advanced caseation in which all the coats and even the vessel contents are transformed into a dense hyaline mass. The corpuscular contents of the vessels are often preserved intact, notwithstanding advanced changes in the vessel walls. Again there are thrombi, hyaline or mixed, in various stages of transformation. Sometimes the vessels are the centre of a tubercular process, in which case their fibrinous contents are continuous with a fibrillated fibrin which extends out into the surrounding tissues. Where the tubercular change is early and begins in the intima, the endothelium is sometimes preserved intact; here there is subendothelial proliferation of the connective tissue cells, forming ejDithelioid cells of a round or jjolyhedral shape, with moderate or abundant protoplasm and small round nuclei. But in other cases there is evidence of endothelial proliferation, these cells enlarging, becoming at times cul)oidal, and forming a lining of two or more rows to the lumen, with occasional complete occlusion.

In the serous membrane the changes are most marked ; on the surface is a dense, opaque, necrotic coat, granular, fibrillated and hyaline. Beneath this is a narrow zone of nuclear fragmentation, while yet below and forming aline of demarcation between the necrotic portion of the serous coat and the scalloped caseous zone of the muscular coat is a narrow band of (Edematous, vascular connective tissue containing a few muscle fasciculi, and showing infiltration with lymphoid, epithelioid, polymorphonuclear and occasional giant cells.

The process is least advanced in the cervix, most advanced in the fundus. In the cervix there is no invasion of the muscular coat, and the vaginal portion contains no evidence of tubercular involvement other than a solitary cellular tubercle under the stratified epithelium in its upper part, and


a cellular proliferation of the corium, gradually disappearing as the outlet is approached.

Among the diffuse tubercular tissue are found numerous homogeneous, highly refractive globules of various sizes, occurring singly or in groups. They show especial affiuity for acid aniline dyes, and also stain intensely with gentian violet. In shape they are invariably round; in size they vary from that of a micrococcus or a basophilic granule to that of a lymphoid cell, some even exceeding this. Their average diameter is that of a red blood corpuscle ; in fact, when uniform in size, and occurring in masses, they are readily mistaken for such in specimens which have been stained with ha^matoxyliu and eosin. The little globules are, however, more homogeneous and solid and more highly refractive than red blood corpuscles. These appear of tenest more or less closely packed within cell bodies, the nuclei of which are still preserved. Sometimes they accompany a more advanced degeneration, in which case the nucleus stains poorly or not at all. Again, they are free from cellular inclusion, and lie in groups or scattered through the tissues. The groups are circular, elongated or irregular, and contain from two to thirty or more members. With Weigert's fibrin stain they stand out conspicuously as deep blue spheres, homogeneous and structureless. With Russell's fuchsin stain they strike a bright red hue; with eosin they stain pink. In many respects they correspond with the hyaline bodies considered by Lubarsch" as a form of albuminous degeneration, found by various observers in both normal and pathological conditions, and described by Russell" as " Fuchsin bodies." In the present case they contain neither nuclei nor spores such as Russell and others have described.

In all three coats of the uterus micrococci are found arranged in pairs, clusters, or chains of greater or less length, numbering from three to sixteen members. They are especially numerous along the superficial caseous zone of the peritoneal coat, where they form a thick, irregialar border and extend deep into all fissures of its necrotic structure. In the muscular coat they are less numerous, and are found for the most part within and about blood-vessels in the bands of the infiltrated tubercle. In the mucous membrane they are again present in considerable number, somewhat sparsely scattered at times or occurring on the surface as dense aggregations. Where scattered, their arrangement is usually in the form of pairs and chains.

Tubercle bacilli are also found in the uterine tissues. They occur in the interior of vessels, either free or enclosed within cells, in the vessel walls, and in the tubercle tissue outside.

The uterine myoma is covered by newly formed connective tissue, with rich infiltration of diffuse and circumscribed tubercles and many pus cells. The capsule is made up of strata of well preserved fibro-muscular bands. But the interior of the tumor is necrotic throughout. Near the surface of the necrotic myoma is a narrow zone of calcareous matter; the walls of all blood-vessels in its vicinity are likewise calcified. A still broader zoueof necrotic myomatous structure, including the calcareous baud, is dotted over with spiculated spherules of golden yellow pigment. No tubercles are seen. Russell's fuchsin bodies are numerous in the tissue covering the myoma, but none are found in its substance. Micro-organisms similar


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to those found iu the utei'us are likewise found in the tubercular coFcring of the tumor.

Uiyhl Fallopian Tube. The mucous membrane of the right Fallopian tube at its uterine end has an almost intact epithelium. In one place, however, the epithelium is wanting, and here the stroma is invaded by a mass of tubercle tissue, some of which has broken off and lies free and degenerating in the centre of the lumen, together with the desquamated epithelium. The middle coat of this part of the tube retains its muscular structure; bands of muscle, however, are separated from each other by serous infiltration or by alternating baiuls of diffuse tubercle tissue. The serous coat is composed of solitary caseous tubercles so blended as to form a continuous scalloped zone. On passing outward from the uterine end the tuliercular process becomes more marked, and when the middle portion of the tube is reached the walls are so intensely involved as to form a thickened necrotic mass, with no evidences of structure except a narrow fibro-cellular zone encircling the tube about 2 mm. from the periphery. The necrotic substance is hyaline in the centre, where it is pierced by a ragged slit- like lumen. It corresponds here with the remains of the mucous membrane. There is nuclear fragmentation within the fibro-cellular zone, and among the nuclear fragments isolated bands of muscle are preserved in scanty nnnil)c'r The surface necrosis corresponds essentially with tliat of the uterine serosa, while the middle fibro cellular zone is continuous with the thickened, cedematous, vascular connective tissue of the uterus, which there formed a line of demarcation between the necrotic portion of the serous coat and the scalloped caseous zone of the muscular coat. Here, as there, it contains a few isolated muscle bundles, the only normal elements of the original Fallojjian tubes. Here, as there, it is infiltrated with tubercular cellular tissue and polymorphonuclear cells, and here, as there, it shows many vascular changes, both sclerotic and tubercular, similar to those described in the uterine muscular coat.

There are numerous dilated lymph spaces and blood-vessels with subeudothelial proliferation or a lining of cuboidal cells. Occasionally a well-defined giant cell takes origin iu the endothelium of a vessel and projects into the lumen, filling it more or less completely. Sometimes such a cell is found free in the vessel. Indeed, the giant cells are numerous thi-oughout the middle coat, and are especially abundant near the necrotic mucosa. They are often situated in little caverns, which are sometimes surrounded by lymphoid cells. Where not so situated, they are more apt to be surrounded by an irregular zone of epithelioid cells. They are elongated or irregularly ovoid in shape, of various sizes, and contain nuclei at their poles or about the periphery, seldom in the centre. Sometimes they are invaded by polymorphonuclear and lymphoid cells.

In the fimbriated extremity the degeneration is extreme. The lumen is considerably dilated, the walls are convoluted and thick. The mucous membrane is composed of three strata representing gradations of tubercular change. Next to the lumen is a narrow necrotic border, which takes an intense eosin stain. It gives occasional evidence of original structure in the preserved outlines of old blood-vessels, of connective


tissue bands, of g^ant cells, and even of an occasional caseous tubercle which has not yet lost its identity by coalescence with the general necrotic border. Outside of this is nuclear fragmentation with structural outlines still better preserved ; while yet beyond is the normal stroma invaded by infiltrated tubercle. Tlie middle coat is a comparatively narrow band of fibrocellular tissue, not yet degenerated, forming less than a third of the whole tubal thickness, .and presenting the same interesting features as the corresponding coat of the middle portion of the tube. The thickest part of the wall is the peritoneal coat; it is entirely involved in an extensive necrosis which is at one time fibrillated, at another granular or hyaline.

The little refractive globules described iu thecellular tubercular tissue of the uterus as Russell's fuchsin bodies are present also in the tube iu considerable number. They lie by preference in the middle coat, in which the tubercle tissue is best preserved. They pi-esent the same general characteristics as the hyaline bodies of the uterus, but are somewhat smaller. Indeed, whereas in the uterus their average diameter is that of a red blood corjjuscle, in the tube their average size is that of a micrococcus ; and, where Weigert's fibrin stain is used, they could readily be mistaken for such, were it not that upon careful examination they show less uniformity in size, take a more solid stain, and because larger globules, both free aud in cells, are found in the same neighborhood. Extra-cellular spheres of large size grouped with smaller hyaline globules are sometimes found occupying open spaces iu the tissues.

The borders of the necrotic zones, both mucous and serous, iu all parts of the tube, are invaded to some depth by deeply staining micrococci, which in form, size, grouping and arrangement in the tissues, resemble the organisms found in the uterine coats. Similar organisms are found at times in the blood-vessels of the middle coat. Tlie streptococci predominate, and the average length of the chains is six members. Tubercular bacilli are likewise found.

Rigid Ovary. The right ovary is somewhat enlarged. Its surface presents a smooth, wavy outline and is covered by a thick, cedematous, vascular connective tissue which contains lymphoid and epithelioid cells, but no giant cells. There are also numerous dilated lymphatic vessels filled with lymphocytes. The edges of this connective tissue covering are ragged and represent the remains of old fibrous adhesions between the ovary and neighboring structures. Deep within the ovarian stroma are several isolated and conglomerate caseous tubercles. There are many advanced corpora fibrosa, aiul an unruptured Graafian follicle in the process of retrograde metamorphosis, liussell's fuchsin bodies are numerous in the tubercular tissue covering the ovary, and iu the ovarian tissue itself. They are present where the degeneration is least advanced, aud may be seen, not only in the tubercular areas, but in association with other degenerative changes — in the hyaline degeneration of corpora fibrosa and in the retrograde metamorphosis of unruptured Graafian follicles.

Streptococci, staphylococci and tubercle bacilli are present. Of these the streptococci are most abundant and occur iu long chains, at times reaching the length of fourteen members. They are located within the lumen of blood-vessels, in the blood-vessel walls, or in the perivascular lymphatics of the


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coimective tissue covering the ovary, and are ofteuest free, but may be found enclosed in cells.

Left Fallopian Tule. The left Fallopian tube has the same general structure as the right, the only difference being that the tubercular lesion is more advanced. The middle portion of the tube is converted into a dense neci'otic cord, the transverse section of which shows a ragged longitudinal rift in the centre of an oval area of hyaline necrotic material. This is surrounded bv a fibro-cellular border, whose surface is roughened by fibrous shreds torn in the process of separation from adjacent structures. The fibro-cellular border corresponds with both middle and outer zones of the other tube. The fimbriated extremity, like its fellow, is extensively degenerated, and the lumen is also much enlarged. Its walls, however, are less uneven and are but half the thickness of those of the corresponding tube. Continuous with the middle portion of the tube the fimbriated extremity likewise has an outer border of fibro-cellular tissue and an inner hyaline necrotic coat. In this tube there are fewer giant cells than in the other, and the tubercle tissue in places shows fibroid change. Russell's fuchsin bodies are present in small number.

The micro-organisms found are similar to those in the other tube.

Thus, while both tubes show in the main the same tubercular lesions, they differ in that the left tube has somewhat thinner walls, contains a smaller number of giant cells, exhibits in places fibroid change, and the thickened necrotic serous coat is wanting.

Left Ovary. The left ovary is smaller than the right and is surrounded by diffuse tubercular tissue. In gland-like spaces near the surface are found great accumulations of nuclei, bound together by hyaline and fibrillated fibrin, and often presenting the appearance of the tubercle giant cell. In this ovary there is but one solitary caseous tubercle, about the size of a split pea, which projects slightly above the surface and dips down into the stroma. Fuchsia bodies and microorganisms are present, resembling in every respect those found in the right ovary.

The Vagina. The vagina shows no tubercular involvement. The elevated greyish white patches observed on macroscopic examination consist of swollen, distorted, stratified epithelial cells. Occasional polymorphonuclear and mononuclear cells have wandered up into the epithelium. There is slight proliferation of the cellular elements in the upper portion of the corium. Fuchsin bodies are found in these proliferating areas. More densely stained globules are seen in the swollen epithelium above. Upon the surface of the mucous membrane there are a few cocci and long bacilli. Within the blood-vessels of the vaginal wall, and especially in the larger ones, cocci occur in pairs and chains, both within cells and outside of them.

The bladder and urethra show nothing abnormal.

Pus Sac. The wall of the pus sac, portions of which remain adherent to the pelvic viscera, is from 4 to 6 mm. in thickness. It consists of three coats not sharply differentiated one from the other. In the inner necrotic coat, which represents about one-third of the thickness of the sac wall, the degeneration is extreme. Its surface is edged by dense aggregations of micrococci which in places extend deep into the


necrotic structure. The middle coat is fibro-cellular and con tains a few isolated clusters of fat cells. It is infiltrated with diffuse tubercular tissue. The outermost coat is not sharply separated from the middle, and differs from this in containing numerous closely packed caseous tubercles. Fuchsin bodies are present as intracellular and extracellular globules. They are of all sizes, and contrary to what occurs elsewhere, they are found in the most advanced necrosis. In such places theytake a less intense gentian-violet stain and merge gradually into the surrounding necrotic structure. Micrococci are found in all three coats arranged in pairs, clusters and chains. They are especially numerous upon the inner surface of the sac, where they form a continuous irregular layer. Tubercle bacilli are also present in small number.

General Viscera.

The lung shows very little that is abnormal. The visceral pleura is considerably thickened and presents an irregular wavy outline. Its surface is covered by a layer of fibrin formed by the coalescence of highly refractive clumps. These, in places, extend deep into the tissues, where they appear as densely hyaline whorls, or the fibrin remains limited to the surface, where it forms a meshwork enclosing polymorphonuclear cells. The more hyaline portions are at times invaded by organizing connective tissue. Beneath the fibrinous covering is a layer of highly vascular granulation tissue which contains closely-set flattened tubercles. These tubercles project here and there between the clumps of hyaline fibrin, extending at times to the surface, or dip down into the lung substance. They are more or less caseous and show the same general structure as the tubercles already described. Where less advanced they contain many giant cells. The deeper layers of the pleura contain dark brown and black granular pigment, both free and enclosed in cells.

The parietal pleura resembles the visceral in its general histological features. It is composed of a superficial laj'er of fibrin, beneath which are granulation tissue and caseous tubercles. Quite beneath is a third layer consisting of cedematous connective tissue, the meshes of which are widely separated by serum and the spaces of which are occupied by swollen mononuclear cells. In the parietal pleura there are small extravasations of blood. Both layers of the pleura contain the fuchsin bodies and basophilic cells. A few pairs and chains of cocci and tubercle bacilli are present.

Liver. The capsule is thickened by tubercular growth. The lobules show dilatation of the central veins and adjacent capillaries. The hepatic cells in the centre of the lobule contain a brownish yellow pigment. The peripheral cells are filled with fatty globules.

Distributed thickly through the liver substance, in close relation with the blood-vessels, are countless tubercles, most of which are of microscopic size. Large nodules evident to the naked eye are less abundant. The former consist for the most part of lymphoid cells or of lymphoid with a central accumulation of epithelioid cells. The larger tubercles are evidently older and exhibit the typical structure of miliary tubercles with advanced central necrosis. There are a few pairs and chains of cocci in the liver capillaries.


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Spleen. The capsule is thickened by a new growth of cellular connective tissue containing caseous miliary tubercles. The spleen parenchyma shows an increase in its cellular elements. Much blood pigment and many red blood corpuscles are found. The arterial walls are considerably thickened, and an occasional hyaline thrombus in one of the smaller vessels is seen. There are numerous tubercles, both young and old, scattered through the splenic substance. Fuchsin bodies are present. Micrococci in pairs, masses and chains are found. They are sometimes arranged within cells, but are usually extra-cellular.

Kidney. The kidney shows parenchymatous and fatty degeneration of the epithelium lining the Malpighian tufts and the convoluted tubules. There is a slight increase of connective tissue, especially under the capsule. The tubules are here compressed, but elsewhere they are at times dilated. Hyaline and granular casts are found. The wedge-shaped area described among the macroscopic lesions is found to consist almost entirely of connective tissue in various stages of development. It compresses the tubules, many of which are completely obliterated ; while others persist with intact epithelium or with lumen distended by hyaline casts. The Malpighian tufts are small and fibrous, and in places are converted into hyaline balls. Indeed, the connective tissue invades all structures in the triangular area, and tubules, blood-vessels and glomeruli are alike involved. The central cyst is lined by cuboidal or flattened epithelium. Its walls appear to contain a large number of muscle fibres which have an irregular arrangement and include masses of lymphoid cells. It is continuous with several smaller tubular dilatations and is undoubtedly a retention cyst. At the apes of the triangle is a large dilated blood-vessel with irregular thickened walls and lumen containing remnants of a probable thrombus. The area resembles an infarct in the process of cicatrization, but for the presence of apparently functioning structures. A few cocci arranged in pairs are found within a blood-vessel of the kidney.

Pancreas. The capsule is considerably thickened by a new growth of connective tissue, alternately fibrous, cellular, vascular and cedematous. Numerous closely-set tubercles are embedded in the capsule. They are round and project beyond the surface, or they may be flattened and elongated. They show the typical structure of cellular, caseous and fibroid tubercles. The capsule contains the fuchsin bodies and masses of micrococci.

Lymph Glands. The bronchial lymph glands are invaded by lymphoid, epithelioid and giant cells and show a tendency to fibroid change. Some of the central arteries are sclerotic, others show tubercular lesions. Masses of basophiles are present in the centre of the glands, especially grouped around blood-vessels, and the fuchsin bodies are found at times occupying the interior of basophilic cells. Micrococci occur in pairs and chains within blood-vessels and in the perivascular connective tissue.

In the mesenteric lymph glands the tubercular process is more advanced. The centre is necrotic, with original structural outlines still preserved. The periphery of the gland retains its lymphoid nodules, but these are invaded by tubercle


tissue. The blood-vessels are thickened, and basophiles are found. The gland is covered by (Edematous tubercular tissue. Diplococci and stajihylococci are numerous in the surrounding connective tissue, and beaded tubercle bacilli are found in the interior of the gland.

The aortic valve, the aorta and the coronary arteries show irregular thickening of the intima due to increase of connective tissue which in places is swollen, and the interstices between the branching connective tissue cells are occupied by translucent, highly refractive masses. Or again, the tissue is non-cellular and diffusely hyaline. On the edge of the aortic valve where it appears necrotic a few diplococci are found.

Fibro-caseous bands. The fibro-caseous bands extending across the abdominal pus cavity, and those in the pleural sac, are made up of fibrillated connective tissue, everywhere invaded by diffuse tubercle tissue and circumscribed tubercles in all stages of gi'owth or of retrograde metamorphosis. The peripheries of the bands consist of necrotic zones edged by a closely packed layer of micrococci. The connective tissue stroma shows every stage of organization from young granulation tissue to dense hyaline bands ; the bloodvessel walls are thin and easily rupture"d, and extravasations of blood are sometimes found. The diffuse tubercle tissue consists for the most part of lymphoid and epithelioid cells grouped usually in the neighborhood of blood-vessels. Few giant cells and some basophiles are found. The tubercles exhibit every stage of growth and of retrogi'ade metamorphosis. At times they present a typical cellular structure with giant cells in the centre. Again, the centre is occupied by a blood-vessel, and the lumen of such vessel may contain well preserved fluid contents, fibrillated fibrin, or a hyaline or mixed thrombus. The caseous peripheral zone is from 2 to 6 mm. in thickness. It contains no cells nor nuclear fragments, but is made upof a structureless necrotic substance, alternately granular, fibrillated and hyaline. Fuchsin bodies are easily demonstrable. They are of all sizes, from that of a basophilic granule to a lymphoid cell, and are both intracellular and extracellular. They occur in the diffuse tubercle tissue where degeneration has just begun. The micrococci found on the surface of the band sometimes extend deep into its substance ; they occur in pairs, in masses and in chains. In the bands of the abdominal pus cavity compressed lobules of adipose tissue exist.

Bacteriological Examinatiox.

Cover-slip preparations made at autopsy from a tubercle upon the pleura demonstrated large numbers of long beaded tubercle bacilli and clusters of micrococci. Cultures made from this tubercle enable one to isolate white, lemon yellow and orange colored colonies Inoculations from these colonies into the various culture media exhibit the peculiar cultural characteristics of the staphylococcus pyogenes aureus, citreus and albus, and cover-slip preparations from the various cultures invariably show cocci arranged in clusters and in pairs. Unfortunately, no cultures could be made from the abdominal viscera, but hardened sections of the organs stained by Gram's, Weigert's and Gabbet's methods exhibit staphylococci, streptococci and tubercle bacilli in all.


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Summary of Histologhcal and Bacteriological examinatiok.

(1) The condition is a mixed infection due to the tubercle bacillus, the streptococcus pyogenes, and the staphylococcus pyogenes aureus, citreus and albus.

(3) Miliary tubercles, both grey and caseous, are found in all the viscera of the body except the heart and pancreas ; in the lymph glands, and in all serous membranes excefit the pericardium.

(3) Diffuse tubercle tissue is found only in the more chronic lesions — in the pelvic viscera, the lymph glands, the pleura, the peritoneum, in the wall of the newly formed abdominal sac, and fibro-caseous bands. In the viscera this is usually cellular, but may be caseous. In the serous membranes it is always caseous.

(4) Tubercle bacilli are numerous in the tubercular lesions throughout the body. They are especially numerous in the pelvic viscera, lymph glands and alidominal pus sac.

(5) The products of ordinary inflammation are often found associated with the tubercular lesions.

(6) Staphylococci are found in all the organs. They are most numerous in the lining of the abdominal pus sac and the tibro-caseous bands.

(7) Streptococci are likewise found throughout the body, but are especially abundant in the pelvic viscera, the pus sac and the fibro-caseous bands.

(8) Kussell's fuchsin bodies are found wherever the tubercular tissue is beginning to degenerate and occasionally where the degeneration is extreme.

(9) The viscera are congested and there is general arteriosclerosis.

Conclusions.

From the clinical history, gross anatomical lesions and histological appearances, we therefore conclude that the disease began as a tubercular inflammation of low grade in the pelvic viscera some time before pregnancy.

That the tubercular process spread by direct extension or by the lymph channels to the anterior part of the abdomen, which thus became shut off from the rest of the peritoneal cavity by chronic adhesions.

That the phenomena incident to pregnancy and the puerperium excited the process to increased activity, to which, either at this time or later, was probably superadded a pyogenic infection.

That this infection remained limited to the pelvic organs because of occlusion of the tubes by previous tubercular adhesions or by the more receutinflammatory process, until manual examination of the already much diseased organs caused unavoidable rupture into the anterior abdominal sac.

The pain, rise of temperature and abdominal distension were the result of the secondary pyogenic infection of this cavity, from which the general infection took place. I The general tubercular infection doubtless spread, partly

by direct extension, partly by the lymph channels, but principally through the blood-vessels. The first two modes of invasion are shown by the extensive diffuse infiltration of all structures continuous with and contiguous to the pelvic viscera


and the abdominal pus sac. Infection through the blood is evidenced by the general miliary tuberculosis of all the viscera of the body.

Tuberculosis of the tubes and peritoneum is usually a secondary condition. It may follow tubercular disease of any organ of the body, but is seen most commonly associated with tuberculosis of the lungs. In this case, however, the process must have originated either in the peritoneum or in the tubes. The lungs showed no old tubercular foci, but were involved only in the general miliary tuberculosis. The pleura was diseased, but to a much less extent than the peritoneum or the tubes. The intestines were not at all involved, and the lymph glands were enlarged and caseous, but not extensively diseased.

The question arises, what was the relation of the tubercular disease in the tubes to that in the peritoneum ? Which was primary, which secondary? Considerable difference of ojnnion exists as to the relation between tubercular peritonitis and tuberculosis of the tubes. In his monograph on "Tubercular Peritonitis" Osier" says: "The Fallopian tubes are often affected, but the proportion given by various writers differs much. It is safe to say, I think, that in .30 to 40 per cent, of the cases in women the tubes are found affected. The process is commonly confined to the distal ends and may be primary — which is usual — or is secondary to the peritoneal involvement."

In this opinion of primary tubal involvement the majority of observers agree.

On the other hand Williams" asserts that "Tuberculosis of the Fallopian tubes is far more frequently of secondary than of primary origin, and when it occurs in combination with tubercular peritonitis, it is far more often the result of than the cause of the latter. The fact that the fimbriated extremity of the tube is the portion most frequently affected is of itself evidence in favor of its secondary origin, and in several cases of tubercular peritonitis we have found tubercles on the exterior ofthe tube and its fimbriated end, but none in its interior,showing that the process was extending from above downward." Among others, Siinger and Borschike confirm his view.

In this case the only indication pointing to the peritoneum as the source of disease is the extensive caseous involvement of its anterior part. On the other hand, primary disease of the tubes is indicated by the still more extensive involvement of their walls, by the presence of numerous giant cells, considered by Baumgarten' as significant of jDrimary tubal disease, and by the clinical history which points to the pelvic organs as the first affected. As shown by the foregoing studies, the fimbriated extremity of the left Fallopian tube must be regarded as the probable starting point of the whole tubercular process.

If then the tubercular disease of the tube is of primary origin, the further question presents itself, how did the disease arise ? Primary tuberculosis of the tubes may originate in two possible ways: (1) By infection through the blood, and (2) by infection from without. Primary infection through the blood is a matter of pure speculation and is highly improbable. The more likely source of infection is through the vagina from without. Although no history of such invasion could


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be obtained in this case, yet it is regarded as tliemost probable portal of entry. The fact that the nterus was less involved than the tube, and that the vagina was not all diseased, does not negative this theory of infection, since the tubercle bacilli, failing to find conditions favorable for their growth until the left fimbriated extremity was reached, here set up their characteristic lesions. Thence they probably sjiread to the fundus of the uterus, to the uterine cavity and cervix, to the opposite tube, and to the peritoneal cavity, from which the general infection took place.

The associated involvement of pleura and peritoneum must be considered of diagnostic value, since coincident inflammation of both these membranes is so often of tubercular origin.

Besides the extensive character of the lesions, there are several unusual features in the case. In the first place, considerable interest attaches to the fuchsin bodies so numerous in this case. These bodies resemble the little globular masses described by Russell"' in 1890 as " a characteristic organisnx of carcinom.a," and correspond in every particular with the description of these bodies as given by Lubarsch' under the head of "Albuminous Degeneration."

There is scarcely a normal condition or pathological process in which they have not been found, but their relation to malignant tumors has been especially noted. They are not of constant occurrence in any pathological change.

With regard to their nature, the view of Eussell that they may be considered as yeast fungi is no longer held. Tliey have been variously interpreted as protozoa, hyaline thrombi, altered Altmann's granules, von Recklinghausen's hyaline, bodies resembling corpora amylacea, transformation of the cell protoplasm, and as a product of the tissue fluids in which a degenerative process is added to a beginning coagulation process.

Lubarsch himself inclines to the view that the Russell's fuchsin bodies ai'e the product of cell protoplasm, the granules of which have undergone certain chemical and physical changes. He believes that they may be due either to a secretion or to a degeneration of the cell, the former occurring in normal conditions, the latter in pathological processes. Lubarsch also refers to the relative increase of basophiles in areasin which the fuchsin bodies abound — a phenomenon noted by Niehus and Klien, and observed also in the present case. In explanation of their coincident occurrence he attributes the formation of the fuchsin bodies to a chemical change and confluence of the granules of the former and some of the wandering cells, and suggests that both are due to active tissue transformation. From the description given in the present case, this mode of origin seems probable.

A second point of interest is the rare combination of tuberculosis in both body and cervix of the uterus. Regarding this Williams" says: "The affection is almost always limited to the body of the uterus, rarely extending beyond the os to involve the cervix ; and of the few cases of tuberculosis of the cervix on record, a considerable portion occurred without any involvement of the rest of the uterus. Tuberculosis of the uterus which also involves the cervix is rarely met with, and as far as we can ascertain from a careful survey of the literature, has ouly been noted in seven cases."


In this connection may also be mentioned the tubercular invasion of the muscular coat of the tube, which, as a rule, escapes involvement even in advanced tuberculosis.

The large sacculated exudation occupying the anterior portion of the peritoneal cavity and simulating ovarian cyst is rare. Among the few recorded cases of tubercular peritonitis with encysted collection of fluid are those reported by Bernutz, Spencer Wells, Gardner, Howard, Erich, Ewing, Mears and Atlee.

A feature of special interest is the thick fibro-caseous band which extends across the pus sac in the median line of the abdomen, and is probably the remains of the rolled-up omentum. In structure it bears some resemblance to the thickened strands described by Klebs' as passing transversely across the abdominal cavity below the umbilicus, and which he attributed to retraction of the omentum. Such omental tumors are not uncommon and have frequently been described. In location, however, this fibro-caseous band does not correspond with the transverse omental tumors, since its direction is anteroposterior and from above downward, and its attachment is by its extremities. In explanation of this formation one can only assume some distortion of the original omentum, with displacement, thickening, caseation and complete transformation into the fibro-caseous band.

In conclusion, I wish to thank Dr. Flexner for valuable suggestions during the course of this work. Dr. B. B. Browne for kindly allowing the use of his clinical notes, and Mr. Max Briklel for the accurate drawing which accompanies the text.

Bibliography.

1. Baumgarten: Zeitschrift f. kliu. Med., Bd. IX and X, Wien, 1885.

2. Oullen, Thos. S. : Tuberculosis of Endometrium. Johns Hopkins Hospital Reports, Vol. IV, Nos. 7 and 8, 1895.

3. Flint: General Jliliary Tuberculosis, Tubercular Peritonitis, Pulmonary Phthisis. Principles and Practice of Medicine, 1886.

4. Gardner: Tuberculosis of Anterior Peritoneal Cavity. Canada Medical Journal, Vol. 13, 1885.

5. Hegar: Monograph, Genital-Tuberculose des AVeibes. Stuttgart, 1886.

6. IIektoen,Ludwig: Vascular Changes of Tubercular Meningitis, especially the Tubercular Endarteritis. The Journal of Experimental Medicine, V^ol. I, No. 1, January, 1896.

7. Howard, Wni. T. : The President's Address, Transactions American Gynaecological Society, Vol. X, 1885.

8. Klebs : Handbuch der path. Anatomie, Bd. I, p. 335.

9. Lubarsch, O., and Ostertag, 0.: Diealbuminosen Degenerationen, Ergebnisse der allgemeinen pathologischen Morphologic und I'hysiologie des Menschen und der Thiere, Vol. II, 1S95.

10. McFarland, Joseph : The (iiant Cell of Tubercle. International Medical Magazine, Vol. I, No. 10, 1892.

11. Osier, Wm. : Tubercular Peritonitis. Johns Hopkins Hospital Reports, Vol. II, 1890.

13. Russell, Wm. : An Address on the Characteristic Organism of Carcinoma. British Medical Journal, Vol. II, 1890.


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13. Williams, J. Whitridge: Tuberculosis of the Female Generative Organs. Johns Hopkins Hospital Reports, Vol. Ill, 1893.

14. Williams, J. Whitridge: Tubercular Peritonitis. Maryland Medical Journal, Vol. 32, K^os. 3 and 4, 1894.

15. Lenhart, C. M. : Tubercular Peritonitis. Medical Record, Vol. XLVIII, October, 1895.

Description of Plate.

Pelvic viscera fixed in formalin and hardened in alcohol, viewed from above. Right tubo-ovariau mass seen in crosssection.


F. U., fundus of uterus.

Right tube, showing cross-sections of tubercular lumen.

r. F. E., fimbriated extremity of right tube.

r. Ov., right ovary.

if., myoma.

Rd. Lig., round ligament (left).

I. T., left tube.

I. F. E., fimbriated extremity of left tube.

I. Ov., left ovary.

From the left surface of the larger myoma projects a fibrocaseous band. To the right is attached a portion of the abdominal pus sac.


A VISIT TO BAD NAUHEIM, WITH THE PURPOSE OF INVESTIGATING THE "SCHOTT TREATMENT" FOR CHRONIC HEART DISEASE.

By C. N. B. Camac, M. D., First Assistant Resident Physician.


Last November, at Dr. Osier's suggestion, we undertook to introduce into the hospital the Schott treatment of exercises and medicated baths for cases of chronic heart disease. After consulting the bibliography of the subject, several cases were placed under treatment according to the instructions contained therein. At once, however, we were confronted by numerous questions, answers to which it seemed quite impossible to find in any of the references at hand. Although the literature dealt at length with changes in the cardiac outline, the position of the cardiac maximum impulse and the respiration, the theories upon which the beneficial effects were based, etc., no answers to such practical questions as the following were given :

(1) Is any massage to be employed during or after the bath ?

(2) What drugs are to be employed daring the treatment, and what drugs are contraindicated ?

(3) Should the baths and exercises be given together; or if separately, which should precede?

(4) Are stimulants to be administered before or after the bath ?

(5) What should be the diet of the patient?

(6) Are cases of hydrothorax or ascites to be tapped ? etc., through quite a list with which it is hardly necessary to weary you.

Finding many of these questions unanswered, it was with considerable interest that I received Dr. Osier's suggestion to visit Bad Nauheim, the home of the treatment and of Dr. Schott, its originator.

Nauheim is in the Grand Duchy of Hesse, three-quarters of an hour from Frankfurt a. M. and two hours from Homburg. Nearly in the centre of the northeastern half of what geologists have called the Mayence Basin (Mainzerbecken) Frankfurt is located, and at the eastern slope of the Johannesburg, the last spur of the Taunus mountains, is situated Bad Nauheim. As one approaches Nauheim he is struck by the great trestlework structures in the midst of the fields. On examining these more closely they are found to be frame structures about


200 to 300 feet long and about 50 feet high, supporting switches closely stacked one upon another. The salt waters are raised to the top of these trestles and allowed to filter through the interlacing switches, upon which, by the evaporation of the water, the salt is deposited. These switches are removed every few months or so, the salt broken from the branches, ground and refined, and serves as the commercial salt of the surrounding country. The most beautiful forms result from these deposits, and by the clever devices of the natives the most grotesque figures are produced. I have some of the figures thus produced.

An estimation of the commercial value of these works today may be made by the value put upon them in 1806, when they were considered by Napoleon an adequate reward to Marshal Louis Nicolas Davout (erroneously written Davoust) for his services in the French army ; and again in 1866, when they fell to Hesse Darmstadt in exchange for Homburg. Since 1834 the reputation of Nauheim for the efficacy of its springs has been steadily coming to the notice of Europeans. Frankfurt up to this time forming the centre and battlefield of many of the German disputes with France, rendered Nauheim scarcely a fit place for invalids.

It was therefore not until 1834 that we begin to hear of Nauheim as a resort for invalids. It was not until 18G0, however, that Dr. Beneke of Marburg considered scientifically the value of the medicated bath treatment. From 1859-1870 several articles by Beneke of Marburg, upon the waters of Nauheim, appeared in the Berlin. Klin. Woch. From 1870 to 1890 August and Theodore Schott and J. Groedel were frequent contributors on this subject to the Berlin. Klin. Woch., also to the Deutsch. Med. Zeitung. August Schott died, but his brother Theodore continued the work, and published in 1892 an article in the Lancet which caused little comment.

In 1894 W. Bezley Thorn became an ardent advocate of the bath treatment, and published an article in the Lancet and also a small book in which he described quite fully the baths and exercises. AVith the appearance of this systematic little book up to the present the treatment has been very popular in


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England. Nauheim, its waters, and the resistance exercises, have been frequent topics in English and German medical journals. lu France and America the treatment has as yet received no very thorough trial. It is interesting to note here the increase in the number of visitors from 1871 to 1895. In 1871 the visitors numbered 5,249; in 1891, 9,244; 1892, 10,272; 1893, 10,-384; 1894, 11,0)81; 1895, 14,136.

Although the season was over when I visited Bad Nauheim, I had the opportunity of seeing the baths through the courtesy of Dr. Hirsch, Dr. Schott's assistant, who showed me over the grounds and described very fully the details of the treatment. It can best be described in Dr. Schott's own words : " The springs of Nauheim may be divided into two classes, those suitable for bathing and those suitable for drinking. Together with other ingredients the bath waters contain from two to three per cent of sodium chloride, from two to three per 1000 of calcium chloride, various salts of iron, above all, very large amounts of carbonic acid.

Coming from the dejiths of the earth, they have a temperature of 83-95° F. Springing from a depth of 180 metres, supercharged with carbonic acid gas by the pressure to which they are subjected, the waters gush far above the surface; for example, spring No. 12 rises to a height of 56 feet and falls again in white seething masses." This is a most sti-iking condition ; so richly charged with carbonic acid are these waters that the reservoir into which they fall has the appearance of a great mass of clouds. " Conveyed directly from the main by means of subterranean pipes, these waters charged with their natural gas are allowed to completely cover the body of the bather. Little bubbles of gas are seen to immediately cover the whole surface of the body; the waters of springs Nos. 7 and 12 escape from a pressui-e of from IJ to 2i atmospheres, and afford a surf bath which compares accurately with the strongest surf bath of sea water."

The first question which arose when this matter came to be scientifically investigated was, how do these baths and exercises act ? That they were vei'y efficacious in the relief of chronic cardiac disease had been demonstrated for some years back, but their action had never been investigated. There are several explanations given :

(1) That given by Dr. Schott in the following woi'ds: " Physiological research of recent years seems to show that the salts held in solution in water externally applied have uo direct action on the system; the light and mobile molecules of the gas, on the other hand, pass rapidly through the skin to the corium with its rich supply of blood. We must look upon the salts held in solution as passing by imbibition through the outermost layer of the epidermis, and so acting on the terminal nerves of the skin as to exert a reflex action on the internal organs. The warm baths act in their own peculiar manner on the organism as a whole ; increased tissue change seems to be induced by an increase of the oxygen absorbing power of the cells, and hence follows the sense of the need of rest and sleep as an immediate consequence of the bath, as well as influences speedily brought to bear on the nervous system as a whole. Excessive bathing induces an excitable state of the nervous system, sleeplessness, loss of appetite and consequent loss of strength. The principal changes which ensue


in the system and in the function of the special organs are that the heart beats more slowly and strongly, the jnilse becomes full and increases in force, and the blood pressure may rise to the extent of 20, 30 mm. of mercury; the breathing becomes regular and quiet, and the capacity of the lungs increased.

While the patient is in the bath he becomes flushed and a feeling of comfort and warmth ensues which may even rise to one of an agreeable intoxicating character. Almost invariably the excretion of urine is increased; exudates in the body cavities, especially from the peritoneum, pericardium and pleura, are absorbed. This latter action and that on the valves of the heart can only be exjjlained on the theory of reflex action produced by influences acting upon the terminal nerves."

Another explanation is that given by Dr. Bezley Thorn, that there is a dilatation of the muscular arteries and afterwards those of the skin, and thus there is a relief of the heart from backward pressure.

In Lauder-Brunton's massage experiments he demonstrates that more blood flows through the massaged part and that blood pressure at first rises and then falls, and that on the conclusion of massage more blood collects in the massaged part. These exjjeriments were confirmed by Dr. Oliver.* T. Grainger Stewartf concludes that the passive exercises (I) improve the circulation of lymph within the tissues, and (2) bring a larger volume of blood into the muscles. He quotes the conclusion of Ludwig to the effect that the capacity of muscles for blood is equal to the combined capacities of the internal organs and the skin. If therefore this be so and Dr. Lai^der-Brunton's experiments be correct, the increased amount of blood in the muscles must indicate a relief of the congestion in the internal organs.

In Dr. Schott's explanation there are two actions :

(1) A cutaneous excitation induced by the mineral and gaseous constituents, and

(2) a more prolonged stimulation of the sensory nerves excited by imbibition into the superficial layer of the corium. The salt producing this excitation is the calcium chloride.

Whatever the explanation of their action may be, two points seem established:

(1) That the apex beat alters its position ;

(2) the area of cardiac dulness is diminished. These two facts, esjDecially the first one, were most strikingly obvious in our first cases, and both facts were most forcibly demonstrated to me in the cases which I saw abroad. One can scarcely credit the results published until he has seen for himself these marked changes.

The case rej^orted by Dr. Bowles in the Practitioner for July, 1896, shows a change of 3 cm. in the apex beat before and after a bath of ten minutes duration, and he says after his visit to Nauheim, which was made for the purpose of seeing for himself, " that which I thought impossible is shown to be quite possible." This case reported by Dr. Bowles was one of chronic myocarditis, moderate pleural effusion, general aiuisarca and general enlargement of the heart. The age of


• Brit. Med. Jour., .Tune 13, 1896. 1 //'«/., September 19, 1896.


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the patient was not given. I shall not at this time attempt to report cases, but merely mention this one of Bowles in order to contirm what has been our experience of the effect of the bath upon the j.osition of the apex beat, and many other reports confirmatory of this remarkable change are to be found in the literature on this subject.

The diagrams of the cardiac outline made by Dr. Bowles are not quite accurate, but there can be little difference in opinion as to the position of the maximum cardiac impulse.

To quote Hr. Schott again: "The methods of administering the baths are of the greatest importance. It is advisable to begin with a 1 per cent salt bath containing Yawn '^^ chloride of calcium, freed from gas and at temperatures varying from 93° to 95° F., the bath lasting from six to eight minutes. The course of treatment should be interrujited by frequent intervals of one day. The temperature of the bath should, if possible, be gradually lowered, while the proportion of solids in solution and the duration of the bath are gradually increased. At a later stage it is permissible to proceed to the baths containing carbonic acid. The temperature may then be rapidly lowered, especially if chloride of calcium be added in order to increase the mineral strength of the bath."

The course consists of six baths: the first and the second being simply with salts, calcium chloride and the sodium chloride; the third, fourth, fifth and sixth contain carbonic acid as well as these salts.

The preparation of the baths artificially was taken up especially by W. Bezley Thorn, in London, in 1895, since which time Ewart, Bowles and Broadbent have employed them in London, Moeller in Brussels, and Heiuemann in New York. Following the analysis of the Nauheim waters made by the chemist Fresenius of Wiesbaden, the artificial baths may be readily prepared. We have now packages made up at our pharmacy each containing the proportion of salts for the different strengths of the baths, each package corresponding to 40 gallons of water, which is just about enough to entirely immerse the body. The baths of different strengths are given to appropriate cases.

I have not attempted in this note in any way to speak for or against the treatment nor to report cases. I have thought it best for the present simply to give an outline of the trip to Bad Nauheim, the purpose of which was to see the effects of the treatment and to learn something about it with the object of trying it in the Hospital here. We have now five cases under treatment, and I trust by keeping careful records of the effects of these baths and exercises that we shall be able to pass judgment upon the weak points as well as the strong points of the method. Only by a careful trial can one place himself in a position either to recommend or to condemn the treatment. I take this opportunity of exjjressiug my apjireciation of the patience with which Dr. Schott heard and answered my many questions. I also wish to thank Dr. Ileineman for the instruction in the movements which he so carefully gave me.

In regard to the exercises, which are worthy of a lengthy description, something must be said. They consist of nineteen movements, each movement restrained by the very lightest resistance. This part of the treatment, under the supervision


of a physician, is entrusted to the nurses, to whom we have given careful instructions as to the method of carrying it out. The following are the instructions which we have laid down for the nurses in the administration of the bath, also the chart showing the observation which should be made.*

Rules fok Schott Bath.

(1) Always understand clearly from the doctor the following points: (V) Strength of the bath to be given; (3) temperature of the bath; (3) length of time patient is to remain in the bath. Note. — Give the bath in the morning unless otherwise ordered.

(3) Observe carefully the chart and note the points therein called for. (1) Give bath on an empty stomach. (2) Note the time from the moment patient is immersed to that when he is taken out. (3) Allow the patient to make as little exertion as possible; assist him in every way. (4) A sheet may be drawn over the tub, but not around the patient. (5) Be sure the entire body is immersed. (6) Keep the finger on the pulse during the entire time the patient is in the bath.

Danger Signals. — Cyanosis (bluing of the face), dyspnoea (diflicult breathing), apncea (gasping), inappreciable pulse. On the appearance of any of these, take the f)atient out of the bath immediately, put him to bed and keej) him as quiet as possible. Friction while in the bath is not necessary, but if the fingers and toes become bluish the extremities may be rubbed slightly towards the trunk. Friction should be cautiously employed ; when the patient is out of the tub rub hini to a glow; give him a glass of milk or cup of bouillon and allow him to rest for an hour.

Diet. — Small quantity q. 4 h. Meat — boiled chicken, mutton chops ; eggs, two a day ; oysters, raw or panned ; vegetables — peas, beans, lettuce; liquids — beef tea, bouillon, cocoa, lemonade, milk. Note. — Never give more than 4 ounces of fluid at a time. Should be sipped. Wine — Port, Ehine, sherry, brandy, dram to half ounce.

Note. — Something light (cocoa and toast) should be taken one-half hour before the bath ; something light and hot (bouillon, milk piuncb and toasted crackers) should be taken directly after the bath. If the heart's action is poor, sherry, brandy or port wine may be given after the bath. Last meal to be taken three hours before retiring.

Bath No. I. Sodium chloride, 4 pounds; cal. chlor., 6 ozs.

Bath No. IT. Sodium chloride, 5 pounds; cal. chlor., 8 ozs.

Bath No. HI. Sodium chloride, 6 pounds; cal. chlor., 10 ounces; sodium bicarb., 6 ounces; HCl, 7 ounces.

Bath No. IV. Sodium chloride, 7 pounds; cal. chlor., 10 ounces; sodium bicarb., 8 ounces; HCl, 13 ounces.

Batli No. V. Sodium chloride, 9 pounds; cal. chlor., 11 ounces; sodium bicarb., 1 pound; HCl, 1 pound.

Bath No. VI. Sodium chloride, 11 pounds; cal. chlor., 12 ounces; sodium bicarb., 1 pound; IICl, 2 pounds.

Each bath consists of 40 gallons of water.

Note. — By using a little more NallCOn than is required


  • These rules are made after perus.al of the literature, also from

instruction obtained from Dr. Schott personally.


104



to take up the HCl, the metal tubs may be employed without doing them auy harm.

NaHCOs + HCl = NaCl + H=0 +00^.


83.75


36.37 The Exercises.*


The exercises are called by Dr. Schott "Widerstandgymnastik," or resistance gymnastics, and consist in slow movements executed by the patient and resisted by the physician or operator. A short interval is allowed after each movement, during which the patient sits down. The exertion employed must be very small, and should cause no increase in resjjiratory movements, flushing or j)allor. The patient should be loosely and lightly clothed, and instructed to breathe quietly. The resistance made should be of such a kind that the patient may always feel himself easily the master. The operator must not grasp or in any way constrict the limb, but should oppose by the hand held flatly. The movements are nineteen in number:

Arm. (1) Arms extended in front of body on a level with shoulder, hands meeting; arms carried out until in line, and brought back to original position. (2) Arms hanging at sides, palms forwards; arms flexed at elbow until tips of fingers touch shoulder, back to original position ; one arm only moved at a time. (3) Arms down, palms forward, arms carried outwards and upwards until thumbs meet over head; back to original position ; one arm only moved at a time. Not always advisable. (4) Hands in front of abdomen, fingers flexed so that the second phalanges touch those of opposite hand; arms raised until hands rest on top of head ; back to original position. (5) Arms down, palms against thighs, arms raised in parallel planes as high as possible; back to original position.

Trunk. (6) Trunk flexed on hips ; return to original position. Resist tvith hoth hands. (7) Trunk rotated to left, to right; return to original position. Resist with both hands. (8) Trunk flexed laterally. Resist with both hands. (9) As No. 1, but fists clenched. Resist with both hands. (10) As No. 2, but fist clenched. Resist with both hands.

Large Arm Movements. (11) Arms down, palms against

  • The description of each movement is taken (with a few modifications) from "Chronic Disease of the Heart" by W. Bezley

Thome.


thighs, each in turn raised forwards and upwards until arm is alongside of ear, then turned outward, and arm descends backwards. Not always safe. (12) Arms down, palms to thighs, both together moved backwards in parallel planes as far as possible without bending the trunk forwards. Not always safe.

Legs. (13) Thighs in turn flexed on trunk, opposite hand resting on chair. (14) Lower extremities in turn extended fully, and bent on trunk forwards and backwards to extreme limits of movement, opposite hand resting on chair. (15) Legs in turn flexed on thigh, both hands on chair. (16) Feet together, lower extremities in turn abducted as far as possible and brought back to original position, opposite hand on chair.

Hands and Feet. (17) The arms, extended horizontally outwards, are rotated from the shoulder-joint to the extreme limits forwards and backwards. (18) The hands in turn are extended and flexed on the forearm to extreme limits, and brought back in line with arm. Resist tuith both hands. (19) The feet in turn are flexed and extended to extreme limits, and then brought back to their natural position. Resist with both hands.

We have arranged these in 5 groups, as in this way they may be more readily committed to memory.

Rules for Operators.

1. Each movement to be performed slowly and evenly at an uniform rate.

2. No movement to be repeated twice in succession in the same limb or group of muscles.

3. Each single or combined movement to be followed by interval of rest. Count five.

4. Patient's breathing should not be accelerated.

I. Avoid. 1. Dilatation of the ala? nasi (dilating of nostrils).

2. Drawing of corners of mouth.

3. Duskiness and pallor of cheeks and lips.

4. Yawning.

5. Sweating.

6. Palpitation.

If any of the above make a complete interval, or if excessive, stop the exercises for the day.

5. Direct patient to breathe regularly. If he holds his breath, make him count in a whisper.

(i. Do not constrict the part which is being moved.


SCHOTT METHOD OF BATHS AND RESISTED MOVEMEN" Diagnosis Name Hospital No.


Johns fi

rs.


0PKIN^


Hospital. Ward



• Balh !

l| ana


TIME


Respiration. Pulse and Heart [P,".|-Jr;?ile f SEE HISTORY '«-n?e\%e°e°jr']



It

as



Date


of samel aud Movements


In bod


Just before


1st halt


2nd halt


Immed. after


10 mtu. after


Pulse Pressure


Calibre of Radial


Point Maximum Impulse,


Remarks



Begin


End


R.


P.


R.


P.


R.


P.


B.


P.


R.


P.


K.


P.


Before


After


Before


After


Before


During


Afterl>Betore


During


Atter














May, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


105


Bibliography.

[Those references without the asterisk the writer was unable to consult. Arranged in chronological onler.]

Beueke, F. W.: Ueber Naiilieim's Soolthermen, etc. Marburg, 1859.

Weitere Mittheihmgen iiber die Wirkungen der Sool thermen Nauheims. Marburg, 1861.

  • Nauheim's Soolthermeu gegen Gelenkrheuiuatismus mit

oder ohne Herzaffection. Berlin, kliu. Wocheuschr., No. 33, 1870, p. 269.

Zur Therapie des Gelenkrheumatismus luid der damit

verbundenen Herzkraukheiten. Berlin, Hirschwald, 1872.

  • Neue Erfahruugen iiber die Wirkungen der kohlen

siiurehaltigeu 8oolthermen Nauheims, etc. Berlin, klin. Wochenschr., 1875, No. 9, p. 109 ; No. 10, p. 134.

  • Groedel, J. : Ein Beitrag zur Behandlung der Lilhniungeu

bei Apoplektikern mit Herzfehlern. Berlin, klin. Med. AVoeheuschr., No. 10, 1878, p. 137.

  • Pneumatometrische Beobachtuugen iiber den Eiufluss

verschiedener Biider auf die Kespiration. Berlin, klin. Wochenschr., No. 32, 1880, p. 314.

  • Die Wirkung der Biider auf das Herz. Berl. klin.

Wochenschrift, 1880, No. 20, p. 438.

  • Zur Behandlung Herzkranker. Berlin, kliu. Wochenschr., No. 35, 1883, p. 381.
  • Schott, T. : Beitrag zur tonisirenden Wirkung kohlensiiurehaltiger Theramalsoolbilder auf's Herz. Berl. klin. Wochenschrift, 1883, No. 28, p. 428.
  • Schott, A. und Theo. : Die Nauheimer Sprudel und Sprudelstrombiider. Berlin, klin. Wochensch., 1884, No. 19, p. 394.
  • Schott, A. : Zur Therapie der chronischen Herzkraukheiten.

Berl. klin. Wochenschrift, No. 33, p. 534. 1885.

Leichtenstern, 0. : General Balneotherapeutics. Ziemssen's Handbook of Therapeutics, Vol. IV, p. 395. London, 1885.

Schott, August: Die Bedeutuug der Gymnastik fiir Diagnose, Prognose und Therapie der Herzkraukheiten. Zeitsch. f. Therapie, 1885.

Schott, Th. : Die Hautresorption und ihre Bedeutuug fiir die Physiologie der Badewirkungen. Deut. Med. Zeitung, 1885.

Oertel, M. J. : Therapeutics of Circulatory Derangements. Ibid., Vol. 7, 1887.

Schott, Th. : Die Behandlung der chronischen Herzkraukheiten. Berlin, Grosser, 1887.

Zur Pathologie und Therapie der Angina Pectoris.

Deut. med. Zeitung, 1888, No. 35-38.

Wiborgh, Aug. : Bad Nauheim, etc. Stockholm, 1888.

Bode, W. : Bad Nauheim, seine Curmittel, Indicationen und Erfolge. Zweite Aufl., Wiesbaden, 1889.

  • Schott, Theodore: Herzkraukheiten. Separat-Abdruck aus

der Keal-Encyc. der gesammten Heilkunde. Wien und Leipzig, 1890. (Reprint.;

  • Zur acuten L^eberanstrengung des Herzens und dereu

Behandlung. 1890. Separ. Abdr. aus den Verhandlungen des IX. Congresses fiir innere Medicin zu Wien. (Eeprint.)

  • Herzkraukheiten. Keal-Encycl. der gesammten Heilkunde. Wien und Leipzig, 1890. (Reprint.)


  • Groedel, J. : Ueber abnorme Herzthiitigkeit in Folge von

lunervationsstoruugen. No. 21, 1890, p. 467.

  • Schott, Theodore: The Treatment of Chronic Diseases of

the Heart by means of Baths and Gymnastics. Lancet, 1891, Vol. I, p. 1143. Concluded on p. 1199. (Reprint.)

Israel, E. : Om Nauheimkur, etc. Copenhagen, 1891.

Schott, Th.: Balneo-therapeutic and Mechano-therapeutics applied to the Treatment of Chronic Heart Disease. Medical Record, No. 7, Vol. XXXIX, 1891.

  • Zur Differentialdiagnose des Pericardialexudats uud

der Herzdilatation. (Reprint.) Berlin, klin. Wocheuschrift, 1891, No. 18.

Ueber Herzneurosen. 1893. Separ. Abdr. aus der Real-Encycl. der gesammten Heilkunde.

  • Moeller: Traitement des maladies du coeur par la methode

des Drs. Schott. Bruxelles, 1893. (Repriut.)

  • Babcock : Schott Method of treating Chronic Diseases of the

Heart. Journal of American Medical Assoc, XXI, pp. 717-734, 1893.

Summers, Guillermo: Tratamiento de las enfermades cronicas del corazon por el metodo del Dr. Schott. Gaceta Medica de Cadiz, 1893.

Groedel: Bad Nauheim and the Treatment of Chronic Heart Disease. St. Petersburg Med. Woch., 1893.

  • Schott, T. : The Mineral Waters of Nauheim, their Action,

Uses and Effects. Eyre & Spottiswoode, London, 1894.

Smyly, P. C. : On the Treatment of Enlarged Heart by Certain Movements as taught by Dr. Schott, Nauheim. Dublin Jour, of Med. Scieu., 1894, Vol. 3, p. 185.

  • Thorne, W. Bezley : Treatment of Chronic Diseases of the

Heart by Baths and Exercises according to the Methods of Dr. Schott. 1894. Churchill, London.

  • Thorne, W. B. : The Treatment of Chronic Diseases of the

Heart by Baths and Exercises according to the Method of Dr. Schott. Lancet, 1894, Vol. I, p. 1117.

  • Wethered, F. J. : The Treatment of Chronic Diseases of the

Heart by Baths and Gymnastics as practised at Nauheim. Brit. Med. Jour., 1894, Vol. II, p. 1045.

  • Brunton, T. L. : The Harveian Oration, 1894. London.

♦Campbell, H. : The Mechanical Treatment of Heart Disease. British Med. Journal, 1894, Vol. 2, p. 1101.

  • Eccles, A. Symous: Mechanotherapy in Chronic Diseases of

the Heart. The Practitioner, 1894, Vol. I, p. 107.

  • Pagenstecher de Mexico, G. : Du traitement balneomechanique des maladies chroniques du coeur d'apres la m6thode des docteurs Schott de Nauheim. Bulletin General

de Therapeutique, Paris, 1894, Nos. 15-30, Juin. (Reprint.)

  • Babcock, Robert H. : Report of Cases of Chronic Heart

Disease treated by the Schott Method of Baths and Gymnastics. N. Y. M. J., LX, pp. 705-710, 1894.

  • Schott, Th. : Zur Behandlung des Fettherzens. Deut. Med.

Wochensch., XX, 561, 1894.

Armstrong: Nauheim Treatment of Chronic Cardiac and Allied Diseases. Liverpool Medico-Chirurgical Journal, July, 1895.

  • Sturge, W. A. : Note ou the Treatment of Dilated Heart as


106



practised at Naiiheim. Brit. Med. Jour., 1895, Vol. I,

p. 537.

  • Thorne, W. B. : Tlie Treatment of Chronic Affections of the

Heart by Baths and Esereises. Brit. Med. Jour., 1895,

Vol. I, p. 524.

  • The Schott Method of Treatment in Chronic Diseases

of the Heart. London, 1895.

  • Practitioner, May, 1895, p. 385. The Treatment of Chronic

Heart Disease by the Method of Dr. Schott, Nauheim. By

John F. H. Broadbeut. With some remarks on the mode

of action of the treatment and its indications. By Sir

William Broadbent, Sen. Physician to St. Mary's Hospital.

  • Thorne, W. B. : The Treatment of Chronic Affection of

the Heart. Brit. Med. Jour., 1895, I, p. 524. Kraus, W. C. : Some Advances in Cardiac Therapeutics. Med.

Press and Circ, Loudon, 1895.

  • CTroedel: The Mechanico-Gymuastic and Balneo-Tliera

peutic Treatment of Chronic Cardiac Disorders. Lancet,

London, pp. 802-804, 1895.

Baths in Cases of Arterio-sclerosis. Deut, Med. Zeitung,

1895.

Green, C. L. : The Treatment of Chronic Heart Disease by the Schott Method. N. W. Lancet, St. Paul, XV, 345-349, 1895.

Pospischil: Hydrotherapie bei organischen Herzkrankheiten. Deutsch. med. Ztg., Berlin, XVI, 581-586, 1895.

de Bosia, H. : Des indications des eaux minerales dans les traitemeut des maladies da coeur. Cong. Franc, de MC'd., Paris, 845-852, 1895.

  • Sauudby, Robert: Remarks on the Nauheim (Schott) Treatment of Heart Disease. B. M. J., Nov. 2, 1895, p. 1081.

Discussion, p. 1129.

Birmingham Medical Review, Vol. XXXVIII, 1895, No.

208.

Fisher, T. : The Treatment of Heart Disease. The Hospital, August 24, 1895.

  • Heinemauu, PI. N. : Experiences with the Physical and Schott

Treatment of Chronic Heart Disease. N. Y. Medical Record, 1896, L, 847-852.

  • Mason, A. L. : The Baths of Nauheim in Heart Disease. Boston M. and S. J., 1896, CXXXV, 302.
  • Morrison, A. : The " Schott Treatment " of Heart Disease.

Practitioner, London, 1896, LVII, 268-275.

♦Report of the Lancet Commission on Balneological and Gymnastic Treatment of Heart Disease at Nauheim. Lancet, London, 1896, II, 619-621.

  • McArthur, A. N. : Heart Disease treated by Saline Baths.

B. M. J., 1896, I, 1384.

♦Carter, A. H. : The Schott Treatment of Heart Disease. Practitioner, 1896, LVII, 166. [No direct bearing upon the treatment.]

  • Erebuske, C. J.: Gymnastics in Heart Disease. Bost. M. &

S. J., 1896, CXXXIV, 610-612. (Discussion) 618-620.

  • Graiipner. Die Balneotherapie der chronischeu Herzkrankheiten, ihrMechanismus und ihre Beziehung zur Dynamik

des Kreislaufs. Deutsche Med. Wochensch., 1896, XXII, 529-531.

Nauheimer Mineralbader und einfache Wasserbader:


ihr Einfluss auf Blutdruck und Herzthiltigkeit. Allg. Med. Centr. Ztg., Berl., 1896, LXV.

Cireene, C. L. : Extreme Dilatation of the Heart due to Valvular Disease, with Special Reference to Treatment by the Schott Method. luternat. Clin., Phila., 1896, 6 s., II, 63-73.

Yeo, F. B. : Rest, Exercise and Baths in the Treatment of Cardiac Affections. luternat. Clinic, Phila., 1896, 6 s., II, 31-42.

Bowles, R. L. : Nauheim and the Schott Treatment of Diseases of the Heart. Med. Press and Circ, London, 1896, N. S., LXI, 339. Discussion, 345.

  • Kingscote, E. : Fifteen Months' Practice of the Schott Methods for the Treatment of Chronic Affections of the Heart.

Lancet, London, 1896, I, 761-7C3.

  • Nebel, H. : The Treatment of Heart Diseases by Baths and

Gymnastics. N. Y. Med. Record, 1896, XLIX, 7)7. (Early literature.)

  • Broadbent, Sir W. N. : Note on Auscultatory Percussion and

the Schott Treatment of Heart Disease. Brit. M. J., 1896, I, 769.

  • Leith, R. F. C. : An Inquiry into the Physiology of the

Action of Thermal Saline Baths and Resistance Exercises in the Treatment of Chronic Heart Disease (the Nauheim and Schott System). Edinb. M. J., 1895-6, XLI, 804, 814. Also Lancet, 1896, I, 757, 841.

♦Campbell, H. : The Schott Treatment of Heart Disease. Lancet, 1896, I, 951. [Communication on Leith's paper.]

  • The Schott Treatment as carried out at Sidmouth. Brit. M.

J., 1896, I, 924.

Anderson, McO. : Dilatation of the Heart treated by Exercises on the Schott Principle. Glasgow M. J., 1896, XLV, 266, 268.

♦Poore, G. V.: Two Cases of Heart Disease treated by Saline Baths. B. M. J., London, 1896, I, 1139.

  • Rives, W. C. : The Baths of Nauheim in the Treatment of

Disease of the Heart and the Therapeutic Methods of the Doctors Schott. N. Y. M. J., 1896, LXIII, 471-479.

Steven, J. L. : On the Nauheim (Schott) Methods of Treatment as applied to Cases of Cardiac Valve Disease of Rheumatic Origin. Glasgow M. J., 1896, XLV, 339-361.

  • Thorne, W. B. : Self -Poisoning in Heart Disease ; its Relation to Schott Methods of Treatment. Lancet, Loudon,

1896, I, 755-757.

♦Schott, T.: Ueber gichtische Herzaffectiouen und dereu Behandlung. Berliner klin. Wochenschrift, XXXIII, 457-519, 1896.

♦Stewart, Grainger: Discussion on Treatment of Cardiac Failure. Brit. Med. Journal, September 19, 1896.

♦Bowles, R. L. : An Experimental Inquiry into the " Schott Treatment" of Certain Diseases of the Heart at Bad Nauheim. The Practitioner, July, 1896. (Reprint.)

♦Ileinenmu, H. Newton: Die physikalische Behandlung der chronischen Herzkrankheiten. Deut. Med. Woch., 1896, No. 33, Leipzig. (Reprint.)

♦Cohen, Solomon Solis : The Schott Method of Gymnastics in Chronic Heart Disease. JIaryland Jledical Journal, Feb. 20, 1897.


May, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


107


A CASE OF POROKERATOSIS WITH


(MIBELLI) OR HYPERKERATOSIS EXCENTRICA (RESPIGHD A REMARKABLE FAMILY HISTORY.*


PKELIMINAEY NOTICE.


By T. Caspar CtILCHRist, M. 11. C. S., L. S. A., Associate in Dermafologi/, Johns Hopki)is Unicersifi/.


In October, 1893, Mibelli, of Italy, described three (slight references were made to three others) cases of a new disease which, after a careful and detailed histological examination, he named Porokeratosis. The disease began at an early age, and was chiefly distributed on the backs of the hands, feet, other portions of the extremities, neck, face and scalp. The lesions commenced as minute, dirty brown, dry, cone-shaped elevations of different sizes and forms, which became much altered as they very slowly increased in size. The lesions extended centrifugally, and the central portion gradually sank in and still remained callous, but the margin was represented by a raised wavy ridge which presented the features of a raised seam. Some patches grew to a very large size and covered almost the whole forearm. Mibelli gave the name porokeratosis to this disease because the most important anatomical lesion was the hyperkeratosis of the sweat duct and sweat pore. In one instance a brother and sister had the disease, mainly on the face and neck. The disease was exceedingly chronic and was unaccompanied by any inflammation or any subjective symptoms.

On January 15, 189-1, Respighi, also of Italy, described seven cases of a disease which was recognized by Mibelli as belonging to the same group. Respighi gave the name of " Hyper


  • Exhibited before the Johns Hopkins Hospital Medical Society,

March 1, 1897.


keratosis excentrica" to this affection. In one of the cases the father of the patient also was affected with similar lesions. Two years later, three more cases were described by the same author. A single case has been recorded outside of Italy, by Dr. M. B. Hutchius, of Atlanta, Ga., in the Journal of Cutaneous and Genito- Urinary Diseases for October, 1890. In Hutchins' case the disease began at two years of age, on the 2)alni of the left hand. The patient is now a man, 33 years old, and has the disease on the left palm, the back of the hand and forearm, and on the face. No histological examination was made. Hutchins compares the boundary of the patches to the "outside of a seam with a thread-like line dividing its lateral halves, and consisting of horny epidermis." No other member of the family had it. In all the cases which have thus far been recorded, only two gave histories of other members of the same family having the disease. In the one case (Mibelli's) a brother had it, and in another (Respighi's), the father of the i^atient had it.

The patient whom I exhibit this evening is a young man, 21 years of age, who has had the disease since he was five years old, when it commenced on his ears, nose, chin, neck, back of hands and right forearm. The lesions were extremely slow in ap2)earing and in growing. The most remarkable feature about the whole case is the family history, which is here given in a tabular form, together with a very brief descrijitiou of the disease in each case.


Grandmother.

Disease on the face ; commeuced when she was a child iu 1813, now dead.


One Brother.

Lesions on the face, oommeucing at an early afie and lasting until death.


Father.


Disease began at about 8 years of age and is on the face, palms, back of hands, forearms, legs, feet, and sole of one foot.


One Brother.

Disease commenced at about 9 years of age, on face and leg; died


One Son. No eruption.


28 years old, married. Disease commenced at 7 years, on face.


Brother 0).

Aged 30 ; four lesions on left side of nose, commenced at 5 yrs.


Brother i2). Aged 17; disease just commencing (?), one lesion on neck.


Aged 15; number «)f lesions on face which began at about 9.


9 years old: disease commenced at 7 and quite extensive on face.


Aged 11; disease commenced at 9 years on face.


108



It will be seen that eleven persons in one family have had this disease. The patient gave me this history after careful inquiry, and I have since been able to verify his statements with reference to seven of the cases, viz. father, three brothers, a married sister and two of her children, by personal observation. The patient's description of the lesions in his father and brothers, whom I examined later, was so correct that I feel confident the other descriptions are also true, especially since the remaining family history was verified by his father and mother. The father of the patient also described to me the disease as it existed on his mother, an uncle and brother. I will not go any further into the history or description of the lesions occurring in other members of the family, but will reserve that for a more detailed histological description with photograph and drawings, which will appear later.

The patient first came under my care eighteen months ago, and my attention was then only directed to the lesions on the face. I did not diagnose the disease until I had made ten or more histological examinations of excised portions and had seen Mibelli's and llespighi's articles.

The eruption consists of lesions of various sizes and forms which appear to take on two characters according to their age. The smallest variety, which are distributed chiefly over the face, consist of minute (less than 1 mm. in diameter), dirty brown, semi-globular elevations of a horny nature. When they reach the size of a small pinhead the centre becomes depressed and the margin in some is slightly raised, round, oval or slightly irregular, and presents the appearance of a raised seam, along the centre of which runs a thin black line. As the patch becomes very slowly larger the base takes on a somewhat atrophic character. In a few of the lesions, especially those on the neck, a number of minute conical elevations are distributed along the ridge, giving it an irregular appearance, and sometimes one or two of these minute cones appear in the central portion of the plaque. The largest patches are about the size of a split pea.

After removing some of the diseased portions with a curette and applying very thoroughly the silver nitrate stick, I


have seen on four or five occasions the disease return within a month or two in the manner described, viz. a very minute, dirty brown papule, which within two or three weeks apparently began to clear up in the centre. Other lesions return in the form of a ring or oval ridge. If one of the patches is curetted it is fairly easily removed, but the operation is followed by almost as much bleeding as the removal of a small epithelioma. Examination of the scrapings, either fresh or after treatment with liquor potassaj, is negative. While watching the course of the disease week by week, I have seen new lesions arise which I had not detected the week previous.

One or two of the lesions appeared to have formed round a hair follicle, but others did not exhibit any such relationship.

A histological examination of a large number of sections from the most recent as well as from the oldest patches showed that the disease consisted of a marked hyperkeratosis of the sweat pore and duct and of the adjacent hair follicle. In some of the material excised from the face it was not clear tliat the hyperkeratosis had commenced in the mouth of a hair follicle, but in other sections, especially of the smallest variety of lesions, the disease had undoubtedly commenced about the sweat pore. The oldest lesion, especially from the ear, presented a picture almost identical with that of a mild psorospermosis foUicularis (Darier).

From the clinical and histological characters of the disease there was no doubt of the diagnosis of all the cases, but the special feature of this rare lesion was perhaps most marked in the case of the father of the patient, who presented on the hands lesions which showed the well-defined raised wavy edge with a thin blackish line along the centre.

The character of the disease on the hands agreed perfectly with the descriptions of Mibelli and Hutchins. JSfibelli has reported 6 cases, Eespighi 10 cases, and Hutchins 1. I am able to record a group of eleven in one family, which fact seems at first sight to point to a strong hereditary taint. The histological features will be discussed in detail and a fuller clinical description will be given in a later article.


A RAPID METHOD OF MAKING PERMANENT SPECIMENS FROM FROZEN SECTIONS BY

THE USE OF FORMALIN.

By Thomas S. Gdllen, M. B., Resident Gynecologist.


In April, 1895, I published two methods under the above title in the Bulletin.

Since then, numerous requests have been made for reprints or for copies of the Bulletin of that number, and as the supply is exhausted, it has been thought best to publish the article again with one or two minor alterations. The methods have been continuously employed in the Hospital, and especially in the gynecological department, and have proved uniformly satisfactory.

A complete freezing outfit has been placed in close proximity to the operating room, so that as little delay as possible may occur in examining a specimen. For example, if a carcinoma


of the uterus is suspected, the patient is brought to the operating room prepared for hysterectomy. The uterus is curetted and the scrapings are examined while the usual preparations for abdominal section are being made. By the time all prejsarations are completed the diagnosis is given; if negative, the patient is returned to the ward with the assurance that there is no cause for alarm ; if positive, the organ is immediately removed. The woman is thus saved from taking an anajsthetic twice, and avoids the period of anxious suspense of four or five days generally required by the ordinary methods to ascertain whether she has malignant trouble or not. Any one who has hardened tissues in formalin will be im


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pressed with the rapidity of its action, with the firm consistence of the tissue, and with the absence of the contraction of the specimen so often seen when alcoliol is used as the hardening medium. Microscopical examination of a specimen hardened in formalin, as we all know, shows almost perfect preservation of the cellular structure. Recently it occurred to me that formalin might be used in the preparation of frozen sections.

One of the greatest difficulties experienced in rendering frozen sections permanent lies in the fact that when passed through alcohol the section frequently not only contracts but contracts irregularly, distorting the specimen ; further, such specimens will often stain imperfectly. The use of formalin will obviate these difficulties, allowing one to make an excellent permanent specimen from the frozen section. My method is as follows: The tissue to be examined is frozen with carbonic acid or ether aud then cut; the sections are then placed in 5 per cent, watery solution of formalin for 3 to 5 minutes, or longer if desired; in 50 per cent, alcohol 3 minutes, and in absolute alcohol 1 minute. The tissue is now thoroughly hardened aud can be treated as an ordinary celloidin section, being stained and mounted in the usual way. On examining this mounted section one might readily take it for a well preserved alcoholic specimen. Supposing we stain with hematoxylin and eosin, the entire process is as follows :

Method I. a. Place the frozen section in 5 per cent. aq. sol. formalin for 3 to 5 minutes.

b. Leave in 50 per cent, alcohol 3 minutes.*

c. In absolute alcohol 1 minute.

d. Wash out in water.

e. Stain in ha^matoxylin for 2 minutes. /. Decolorize in acid alcohol.

g. Rinse in water.

h. Stain with eosin.

i. Transfer to 95 j)er cent, alcohol.

j. Pass through absolute alcohol, then through either creasote or oil of cloves, and mount in Canada balsam.

The blood is lost in frozen sections. To overcome this Prof. Welch suggested that the sjiecimen be first fixed in formalin and then frozen. I tried this aud found that we were able to preserve the blood, but that it did not stain very distinctly. For convenience this second procedure will be called method II. The essential factor is the same in each case. The latter process, however, requires at least two hours. A small piece of the tissue is thrown into 10 per cent, solution formalin for two or three hours. It is then put on the freezing microtome and thin sections can be readily made. The sections are stained in the usual way. The detailed procedure of method II is as follows:


  • The sliglit modification of Method 1, recently suggested by L.

Pick, Centralblalt f. Gyn., Bd. XX, S. 1016, 1896, I cannot recomirieiul. When first experimenting with formalin, among other prolures I tried staining the sections after hardening in the formalin I before placing them in alcohol, as Pick now suggests. The ifsulls were fair, but the definition so obtained was not to be compared with that gained by first passing through 60 per cent, and absolute alcohol for the short period. I accordingly abandoned it and did not think it worthy of publication.


Metliod II. a. A piece of tissue lx.5x.2 cm. is placed in 10 per cent. aq. sol. formalin for 3 hours. Rinsed in water.

1). Frozen sections are made.

c. Left in 50 per cent, alcohol 3 minutes.*

(/. In absolute alcohol 1 minute.

e. The sections are now run through water and stained in hsematoxylin for 3 minutes.

/. Decolorized in acid alcohol.

g. Rinsed in water.

/;. Stained in eosin.

/. Transferred to 95 per cent, alcohol.

j. Passed through absolute alcohol, then either through creasote or oil of cloves, and mounted in Canada balsam.

For ordinary use method I is all that is required. Given a piece of tumor from the operating room, it is possible to give as definite a report in 15 minutes as one would be able to give after examining the alcoholic or Miiller's fl.uid sjjecinieus at the expiration of two weeks. Method II is of especial value in the examination of uterine scrapings. Instead of putting them in the 95 per cent, alcohol in the operating room, they may be immediately dropped into 10 per cent. aq. sol. formalin. By the time the pathologist receives them, which is at least two hours afterwards, they are firm enough to be frozen without difficulty, and permanent sections can be immediately made. The second method is to be recommended for all delicate tissues. In employing these methods one must remember, as for example in epithelioma, that some of the cell-nests will drop out, there not being anything to hold them in situ, as there is when celloidin is used. AYe have, however, hardened and stained epithelioma of the cervix by this method without the slightest difficulty.


NOTICE.

All inquiries concerning the admission of free, part pay, or private patients to the Johns Hopkins Hospital 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 $5.00 per week has been established. The Superintendent has authority to modify these terms to meet the necessity of urgent cases.

The Hospital is designed for cases of acute disease. Cases of chronic disease 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 $20.00 to $35.00 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 specialist, 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.

One week's board is payable when a patient is admitted.

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL

Bv John s. lin.i.iNos, M. D., LL. D. C.mtalulng 60 Urgo cjuartu pl.-iiofl, phototyDOS, and llth<.gi-apli», wli.h vIbwb lilaua and detail drawings ot all tUo bulldiugs, aud Uielr liuerl"!- arranguniouts— also wood-cuts of apparatus and flxtures; also U6 pages of letter-press describing the plans followed In the cnnstruoUou, and giving full details ot heatlug-apparatua, ventilation, sewerage and plumbing. Price, bound In cloth, $7.50.



PROCEEDINGS OF SOCIETIES THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of December 7, 1896.

Dr. Thayer in the Chair.

Typlioid Perforation treated by Surgical Operation.— Dr.

FiNNKY.

In 1762 Richter, in Vienna, first suggested the advisability of oiJeuiug and draining the peritoneal cavity in cases of general suppurative peritonitis. The operation did not come to general notice, however, until 1884, and was not applied to cases of suspected perforation of the intestine in typhoid fever until 1887. Since that date 46 cases have been reported, to which may be added 6 unpublished cases, including 3 of Dr. Finney's, making a total of 53.

According to statistics taken from various sources, perforation of the intestine occurs in from 1 per cent, to 2 per cent. of all typhoid fever cases. In 80 per cent, of the cases it occurs in a thickened and iutlamed Peyer's patch of the ileum, from 2 cm. to 1 m. above the ileo-cascal valve. In over 12 per cent, it occurs in the large intestine, and in 5 per cent, in the appendix vermiformis. There is usually but one perforation. In twelve cases, however, multiple inflamed Peyer's patches were observed. It occurs more often in men than in women ; more frequently between the ages of 20 and 30 years, and usually during the third week of the disease. The duration of life is usually short. In typhoid fever, perforation is always followed by suppurative peritonitis, either general or local ; howevei', peritonitis may arise during the fever without any discoverable perforation. It occurs much more frequently in mild than in severe forms, and the symptoms may be severe, mild, or wanting. The most constant and characteristic symptom is sudden, severe abdominal pain, persisting with increasing intensity ; there may be collapse, nausea and vomiting. A few of the cases have shown chill, hiccough, a marked fall of temperature, and absence of the liver dulness. Owing to the great difficulties of diagnosis it is impossible to get data as to the number of recoveries without operation.

A study of the reports of the operations brings out the following facts. The time between theonsetof the symptoms of perforation and the oj)eration varied between 2 and 12 hours. The condition of the patients at the time of operation was usually markedly unfavorable. Ether and chloroform were used about equally ; in one case both were used. The median incision was the most common. Thirty-three of the cases showed marked general septic peritonitis with foul pus and exudate. Faecal matter was usually present, and the mesenteric glands opposite the ulcerated Peyer's patches were, as a rule, enlarged and softened. In the treatment, irrigation of the peritoneal cavity was employed more often than simply wiping. As regards the perforation itself, in 8 cases the edges were incised before suturing; in 2 a wedge-shaped piece of the bowel was removed, and in 1 the edges of the bowel were stitched to tlie abdominal wound while an artificial anus was established. Including all of the 52 cases, there have been 17 recoveries; but if doubtful cases are excluded, the result is


13 recoveries from 47 cases,making a percentage of 27.65. In 19 of the fatal cases autopsies were obtained.

These data are hardly sufficient for general conclusions, but several points are brought out quite prominently in studying the group as a whole. The best time for operation is apparently as soon as possible after the patient has recovered from the shock attending the perforation. This is usually in a few hours. There is a remarkable uniformity in the condition of the peritoneum and viscera ; intense congestion, much feculent pus and exudate, with distension of the bowel. As the ileum is the usual place of perforation, it should be examined first ; a suture should be taken over any suspicious-looking patches, and the appendix should be removed if it be at all abnormal. If the inflammation does not involve the whole peritoneal surface, irrigation with the necessarily mild fluids might tend to spread the infection. In dealing with the perforation, to excise the edges takes too long, and healing usually takes place without. Should the wall be in such a condition as to make suture impossible, it would be better to pull out the loop of intestine and leave it until the patient had recovered from his fever. The line of suture must be determined by circumstances; the mattress suture of Halsted is to be preferred. Drainage should always be employed. The fact that in 8 cases a wrong diagnosis was made shows how little dependence can be placed on the so-called characteristic symptoms. However, the systematic examination of the blood promises to be of the greatest assistance. During typhoid fever there is no leucocytosis, but immediately after a perforation a marked increase in the number of white corpuscles occurs. Cabot mentions a case of 8,300 before and 24,000 after ; in Porter's case the figures are 6,500 and 10,600 ; in his (Dr. Finney's), 3,000 and 16,400.

Fitz has pointed out the striking similarity of the symptoms of typhoid perforation to those of inflammation of the appendix. Dieulafoy recognizes two forms of typhoid appendicitis capable of producing peritonitis ; one, "peritonitis by propagation," involving the lymphoid tissue of the appendix, the other, " para-appendicitis," which is of the usual variety.

The symptoms of peritonitis quickly follow perforation. Examination shows that pyogenic cocci, especially the streptococcus pyogenes, are rarely absent, indicating that they are common inhabitants of the intestine. The Johns Hopkins Hospital autopsy reports show in 4 cases a mixed infection of streptococcus pyogenes and bacillus coli communis, in one a pure culture of the streptococcus, and in one a pure culture of the colon bacillus. The absence of the bacillus of Eberth and Gaifky is probably due to its being destroyed by its more active companions, streptococcus pyogenes and bacillus coli communis. In Dr. Finney's third case pure colon bacillus was found; in other cases the typhoid bacilli were present in liver or spleen or in a peritoneal abscess.

As regards the incision, the median has obvious advantages in general, but if the abdominal muscles are too rigid, it is lielter made over the part most often affected. Its length should always be amply suflicient. On the other hand, the


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time consumed in operation should be as short as possible. The autopsies showed that healing was always well under way. Death usually occurred from septic absorption, but the records show some other complications, obstruction of the intestine, a second perforation, defective drainage or an abscess. General peritonitis makes a case very serious, but with operation the chances are about 1 in 4. The treatment of a case of perforating typhoid ulcer involves three things: (1) Finding and closing the perforation ; (3) emptying and cleansing the peritoneal cavity; (3) the establishment and maintenance of effective drainage.

For these ends the following method, employed in his (Dr. Finney's) third case, has proved the most satisfactory. An oblique incision, about 6 inches, is made in the right iliac fossa. The Ciscum is found as a guide to the ileum (or appendix); the coils of small intestine, beginning with the ileum, are pulled out systematically. One assistant wipes vigorously and thoroughly the coils with a gauze sponge wrung out of hot salt solution as they are withdrawn, while another keeps them covered with warm sterile gauze. If necessary the entire small intestine is pulled out through the wound and laid to one side, covered with warm gauze. The peritoneal cavity is then wiped out thoroughly, and the coils uncovered and irrigated outside the abdomen with hot salt solution. They are then replaced in the abdomen. The worst or sutured coil is placed with its suture next the abdominal wound, and is packed about with strips of bismuth gauze to insure good drainage. The abdominal wound is closed tightly except a small opening for the gauze drain. In case of distension the bowels should be moved early and thoroughly by calomel in broken doses, followed by salts, and if necessary, a high turpentine and soapsuds enema. If stimulation is necessary, use hypodermics of strychnia, enemata of hot black coffee, or transfusion of a quart or more of the normal salt solution into the cellular tissues under the breast.

Finally, in summing up the experience of himself and others, he concludes that (1) of all the so-called diagnostic signs of perforating typhoid ulcer, most reliance is to be placed upon the development during the third or fourth week of an attack of typhoid fever, of severe, continued abdominal pain, coupled with nausea and vomiting, and at the same time a marked increase in the number of white blood corpuscles.

(2) The surgical is the only rational treatment of perforating typhoid ulcer. •

(3) There is no contraindication to the operation, surgically speaking, save a moribund condition of the patient.*

Case I. — Mr. M.,aged about fifty-five years, was taken sick about October 15, 1894, complaining of headaclie, general malaise, pains in limbs and joints, togettier with irritability of the bladder. Was


•Since the above was written one other case has been reported by Armstrong, of Montreal (Montreal Med. Journal, Vol. XXV, No. 8, 1897). This case recovered from an operation for the relief of first perforation. Twenty-four days later, however, a second, and four days later a third perforation occurred, from the effects of which the patient finally succumbed. Reference is also made to the fact that two other fatal cases had occurred in that vicinity.


seen on October 19 by his physician, Dr. Wesley C. Stick, of Glenville, Pa., to whom I am indebted for the notes of the case. " He gave an indefinite history of having felt badly for about ten days. He had at this time a temperature of 102° F., frequent micturition, bowels constipated, pulse 100. Patient up and dressed ; was put to bed and bowels opened by enemata. In a few days temperature came down to about 100° F., pulse to 90. Would not stay in bed. Irritation of bladder ceased. Was getting along very nicely until the night of October 2(ith, when he was suddenly seized witli a violent pain in his abdomen while lying in bed. Was seen the next morning. Pain in abdomen very severe, relieved somewhat by emptying the over-distended bladder through a catheter. He had been unable to void urine during the night, although having frequent and urgent desire to do so. Several hypodermics of morphine were necessary, however, before he became easy. An enema was given with little result. His abdomen was moderately distended, and not very tender to the touch. In the evening of the same day he was seen again and found to have considerable pain, which was relieved by a hypodermic. Had vomited some during the day. His pulse was about 90 ; temperature 99° to 100° F. The following day, October 28, he vomited frequently a coffee-ground-looking fluid. On the fourth day, October 29, his condition remained about the same ; he could get in and out of bed by himself (he was a largeframed, heavy man, weighing about 225 pounds) ; pulse regular and not above 90 ; cheerful ; the constant regurgitation of coffee-ground fluid being the most troublesome symptom. On the next day, October 30, he was able to sit up in bed, but his pulse had risen to 100 and his temperature to 100° F. Abdomen still not much distended nor very tender."

I saw him at eleven o'clock the night of October 30; his condition then was fairly good, temperature and pulse about 100. Abdomen not much distended, rather retracted ; muscles, especially the recti, very rigid ; tenderness general, but not marked ; frequent and copious vomiting of a dark brownish fluid ; countenance pallid and anxious. The diagnosis was general peritonitis, cause unknown, probably appendicitis, although Dr. Stick had from the first suspected typhoid fever with a subsequent perforation of the intestine. The patient had been exposed to typhoid contagion during a recent visit.

As his condition was evidently becoming worse, it was thought best to open the abdomen. The operation was accordingly performed, and under most disadvantageous conditions, about midnight, in a small log house, with very poor light. On opening the peritoneum it was found to be everywhere intensely congested, of a dark chocolate color ; the coils of intestine distended and covered here and there with flakes of exudate. There was a considerable quantity of turbid feculent fluid everywhere in the abdomen. A perforation was found in the ileum, about six inches from the cKcum, about one and a half centimetres in diameter, with sloughy edges. These were turned in and sutured with Halsted's mattress suture. The peritoneal cavity was cleansed as thoroughly as possible by sponging, the sutured coil irrigated with salt solution and replaced. The appendix was found normal, save the inflammation of its serous covering. The abdominal cavity was thoroughly drained with strips of iodoform gauze, the ends of which were brought out through the wound. The operation took about one hour. His condition at the end was somewhat collapsed, but he rallied under stimulation, administered hypodermically and by rectum. He began to fail, however, and died about seven hours after the operation. No autopsy.

Case II.— J. P. D., aged twenty-six years; single; American; tailor; entered the Medical Ward of Johns Hopkins Hospital, August 3, 1895. Family history is negative, except that his father died of some intestinal trouble, the nature of which was unknown, and one brother died, a year ago, of typhoid fever.

Has had diseases of childhood and several attacks of chills and


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[No. 74.


fever at varying intervals. With these exceptions has been well. Smokes much, does not ilrink, denies venereal contagion. Present illness l)egan six days before entrance, with severe frontal lieadaches and a slight chill followed by fever. These symptoms have persisted, together with anorexia ; no nose-bleed. For past two days, diarrhoea ; has vomited twice ; slight abdominal pain, especially before micturition. Temperature on admission, 103.8° F.; pulse, 92. Blood examination negative as to malarial organism ; abdomen generally tender, slightly distended ; no rose spots ; spleen palpal)le. Leucocytes 3000 per cubic millimetre.

The patient's disease ran a more or less typical severe typhoid course, up to August 16, a. m., thirteen days after entering the hospital, when the following note appeared in the medical history: " Last night patient began to complain of a sharp pain at base of penis, notrelieved by catheterization. Temperature has been rather higher, reaching 105° F., pulse 108, regular, though soft and dicrotic. Very nervous ; abdomen very tense, though not greatly distended. Everywhere tympanitic ; complains of pain ; tenderness marked ; tongue coated ; sweating profusely, and frequently cries out with pain ; baths discontinued and cold sponging substituted." P. M. " Patient has been comparatively quiet since a. m., but at about 4 p. m. liegan to cry out and complain of intense pain in abdomen. Morphine administered hypodermically. Leucocytes, 16,400 per cubic millimetre."

The patient was seen by me with Dr. Thayer at 9.30 p. m., and operation decided upon.

Operatio7i. — Median incision. Peritoneal cavity filled with cloudy, sero-purulent fluid. Peritoneum dark red and much congested. Coils of intestine distended and covered here and there by flakes of lymph. A single perforation, about one centimetre in diameter, was found in the ileum, about sixteen centimetres from ileo-csecal valve. It was situated, apparently, in the centre of a thickened Peyer's patch, and had sharply punched-out edges. Numbers of raised, red areas could be seen here and there along the lower few feet of the ileum. The loop containing the perforation was drawn out of the abdomen, carefully cleaned of the exuded lymph and fiEcal matter, and the rent closed transversely with eight fine, black-silk mattress sutures (Halsted's). Owing to the rigidity of the abdominal walls and the distension of the bowels, puncture of the intestine in several places was necessary, in order to allow of the escape of gas. The loops of intestine were carefully cleansed by irrigation with hot salt solution, and the entire peritoneal cavity thoroughly wiped out with dry gauze. Iodoform gauze was used for drainage, and the abdominal wound closed except where the gauze drainage was brought out.

At end of operation, which lasted a little over an hour, the patient was somewhat collapsed ; temperature 103.3° F. ; pulse, 150 ; respiration, 56. He recovered from this somewhat, under vigorous stimulation, and in four hours his temperature was 101.6° F.; pulse, 130 ; and respiration, 28. His condition did not change materially, except that he became gradually weaker, and died twenty-six hours after the operation. I regret to say tliat no bacteriological examination was made, and no autopsy allowed.

C.\seIII. — Charles H., German, aged forty-seven years; married; laborer; admitted to Johns Hopkins Hospital, .\ugust 15, 1896. Family history good ; no cancer or tuberculosis. Has had the usual diseases of childhood, since which time has been strong and well, except an attack of malaria with chills and fevers eight years ago. I'his attack lasted four weeks. Denies venereal disease; smokes and drinks in moderation. One week before was taken ill with a lieadache, general malaise, and loss of appetite, and later in the day had a distinct chill, followed by fever. Next day felt somewhat better, but was weak and unable to work. He kept in bed until his admission to the hospital one week later. During this time had had several chills and more or less fever, appetite fairly good, but had eaten nothing but liquids and soft solids. He had no


epistaxis nor vomiting ; no pain, nod-arrhoea, bowels had been regular. At about 8 o'clock on the evening before admission (August 14), wliile at stool, he was seized with sharp, stabbing pains in right side of abdomen, with marked tenderness to the touch. Nauseaand vomiting were present. His physician was called in and gave him morphine hypodermically, which relieved thepain. He passedafairly comfortable night and was brought to the hospital early the next a. m., when the following condition was noted :

Face pallid and expression anxious ; tongue coated, margin and tip clean and red. Temperature, 101° F.; pulse, 116, regular and of good volume. Lungs and heart negative ; alidomen is uniformly distended, no undue prominence in any region noted ; skin normal; tympanitic throughout ; rigidity of abdominal muscles throughout, especially of the right rectus in its lower part. In iliac region indistinct tumefaction felt ; tenderness general, but more markeil over right lower quadrant. Rectal examination negative ; no eruption on skin ; urine showed nothing abnormal.

A diagnosis of beginning general peritonitis, jirobably due to appendicitis, was made. I confess, at the time, the possibility of perforating typhoid ulcer did not occur to me.

Immediate operation advised and agreed to. After the usual ])reliminary preparation the abdomen was opened through an incision along outer border of right rectus. Abdominal wall distinctly cedematous. The peritoneum was everywhere intensely congested, roughened and dull, with flakes of plastic lymph. In the pockets between coils of intestine and extending down into the pelvis there was an accumulation of thin, yellowish, turbid fluid, containing flakes of exudate. There was no marked fsecal odor to this fluid. The intestines were distended, congested, and dark colored. In passing towards the median line and hypogastric region the congestion and peritonitis became less marked, and in the upper left quadrant the peritoneum seemed fairly normal. At no place was there the slightest attempt apparent at walling off the inflammatory process. The appendix was found in its normal position, somewhat thickened and congested, and constricted at about its centre, due to old adhesions. It was ligated, excised, and stump covered with peritoneal cuflf. About fourteen inches from ileo-cascal valve, in the ileum on its free border, a small hole, about four millimetres in diameter, was found. It was sharply defined, edges bright red and thickened. It was in the middle of what appeared to be a swollen and enlarged Pej'er's patch. Soft yellow ftecal matter was exuding from the opening. Opposite the ulcer was a mesenteric gland enlarged to the size of an olive, soft and of a bright red color. The loop of ileum was brought out through the wound and packed about with gauze. The edges of the ulcer were turned in and sutured with eight mattress sutures of fine black silk. The edges of the ulcer were not excised. After suturing, the loop was thoroughly cleansed with salt solution and dry gauze and returned, the peritoneal cavity thoroughly and systematically wiped out with pledgets of dry gauze. Some distance below in the ileum a second swollen Peyer's patch could be made out. Bismuth gauze in strips was packed loosely about the sutured portion, and theends brought out through the lower end of the incision. Tiie rest of it was closed with buried sutures of silver wire. The wound was dressed with silver foil and sterile gauze. His condition at the end of the operation was good. Time of operation one and a half hours. Pulse, 120, and of good volume ; respiration. 20 to 25, regular ; color good ; no sweating or coldness of extremities. Shortly after operation an enema of several ounces of black coffee and peptonized milk given.

August 16. Patient passed a fairly comfortable night. Pain not so severe as before oi>eration ; very little ^listension ; says he feels better. Temperature and pulse still somewhat elevated, 102° F. and 110 respectively. liis general condition improved steadily forabout a week, when his temperature and pulse began to go up a little. His tongue became more coated, but abdomen not distended nor tender. Spleen not palpable ; no rose spots. An offensive discharge


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of pus from the right ear indicated an otitis media. About this time a severe pain in the lower part of left thorax developed. Auscultation detected a slight friction rub beginning just below the nipple and running into axillary line.

Blood cultures aspirated from spleen were negative. His temperature and pulse almost reached the normal on August 28, and remained there for a week, when a sharp rise, accompanied by a chill, occurred. His second relapse was quite a severe and prolonged one, so much so that he was transferred to Dr. Osier's ward, where he could be given the cold-bath treatment more conveniently. On September 14 the following note was made by Dr. Osier: " Tongue a little dry ; temperature has been continuously elevated since Septembers. Between 6th and 9th not above 100° F. Since 9th above 101° F. On the 12th and 13th, 104°, and on 14th, 105° F.; pulse, 128. Complains of pain in abdomen, which is fiat and natural looking. Respiratory movements well marked ; no tension ; everywhere soft. Pain referred to hypogastric region and about navel. Edge of spleen not palpable." During the ten days, from September 17 to 27, his temperature ranged about 103° F., occasionally going above 104° F. He was given thirty-eight tubbaths during this period. It reached the normal on October 6, and remained there.

During this time he developed great tenderness in the toes of both feet, and extending up the front of right leg to the knee was some redness and stiffness. This gradually subsided. Several small furuncles on buttocks and sacrum appeared, which were opened. On October 23 he was well enough to be up for the first time. Improved steadily up to November 2, when a phlebitis of right femoral vein with pain and swelling of leg developed. This gradually subsided, and he eventually made a perfect recovery.

Cultures taken at the time of operation from the peritoneal cavity and edges of ulcer showed pure culture of bacillus coli communis.

Dr. OsLER. — It may interest you to know of the number of cases of perforation in our series. Since the hospital opened we have had about 530 cases (I have not the exact figures for this year) of typhoid fever, with 48 deaths, of which 16 occurred from perforation. The percentage of death from this cause is unusually high, for I think Dr. Finney mentioned it was the cause of death only in about six per cent, of the fatal cases.

That two of Dr. Finney's cases were supposed to be appendicitis is a point of great interest. It is not the first nor will it be the last time that this mistake has been made. There are instances in which patients with typhoid fever without perforation have been operated upon for appendicitis with a fever of five or six days' duration and a swelling in the right iliac fossa. Patient has been admitted to the hospital, operated upon for apjiendicitis, no perforation found, but an enlarged ileum and swollen mesenteric glands. It is to be borne in mind, however, how frequent is perforation of the appendix among cases of perforation in typhoid. We have had at least four or five in our cases. There have been two cases of recovery in which symptoms of appendicitis in typhoid seemed very clear.

One word as to the time of the operation. This case was unusually favorable inasmuch as it was seen early and the perforation occurred before the 8th day, which is, perhaps, as soon as ever it occurs in typhoid fever. I think the very early and the very late cases will probably be the most favorable for operation. The statistics that Dr. Finney gives are certainly most encouraging.


NOTES ON NEW BOOKS.

Transactions of the American Pediatric Society, held at Virginia

Hot Springs, May 27, 28, 29, 1895. Edited by Floyd M. Cran DALL. (Philadelphia, 1896. Reprinted from the Archives of

Pediatrics.)

The meetings of this society are characterized by the practical papers presented and the general discussion of them by the members present.

The present report of its seventh session contains a number of articles relative to the more important diseases of infancy and childhood, with discussion of many of the newer remedies. The list of contributors includes many of the best-known writers on the subjects mentioned.

The treatment of diphtheria with antitoxin as an immunizing agent, and its toxic effects, are especially dwelt upon. A resolution was finally adopted that in the opinion of the society the evidences thus far produced of the beneficial action of this remedy justify its further and extensive trial.

Several papers on anomalous forms of scarlet fever and eruptions simulating this disease, and one on the use of icthyol ointment for the local treatment of the eruption of scarlet fever, are worthy of special notice.

With regard to the use of the antitoxin of tetanus in tetanus of the newborn, the evidence seems to show that up to this time it is uncertain in its action, and that chloral hydrate with one of the bromides is to be preferred.

The antitoxin of erysipelas seems to have had no influence in treatment of sarcoma of the kidney, but the author of the paper is inclined to the view that any foreign substance injected into or near the substance of a sarcoma tends to effect a cure, by setting up degenerative changes in the neoplasm, hence the apparent favorable action of erysipelas antitoxin in sarcomata which are external and accessible, and its failure in visceral sarcomata.

There are also papers on purulent otitis media, " inanition " fever in the newly born, the frequency of typhoid fever in children under three or four years, hyperpyrexia, pygopagus, the neuroses of childhood, tetany, symmetrical gangrene following scarlet fever, angina resembling diphtheria with absence of the bacillus, cardiac anomaly, and the association of enormous heart hypertrophy, chronic proliferative peritonitis and recurring ascites with adherent pericardium, in which the view is expressed of the probable progress of the chronic proliferative process along the veins, through the diaphragm, until it involves the peritoneum.

The report is in good type, well edited and arranged.


BOOKS RECEIVED.


A Collection of the Published Writings of William Withey Oull, Bart., M. D., F. R. S. Edited by Theodore Dyke Acland, M. D. Memoir and Addresses. 1806. 8vo. 184 pages. The New Sydenham Society, London.

Proceedings of the American Medico-Psychological Association, at the Fifty-Second Annual Meeting, held in Boston, May 26-29, 1896. 8vo. 332 pages. Published by American Medico-Psychological Association.

Saint Thomas's Hospital Reports. New Series. Edited by Dr. T. D. Acland and Mr. Bernard Pitts. . Vol. XXIV. 1897. 8vo. 510 -i118 pages. J. and A. Churchill, London.

Archives of Clinical Skiagraphy. Edited by Sydney Rowland, B. A. Camb. Vol. I, No. 3, December, 1896. Fol. The Rebman Pub. Co., Limited, London.

Pathological Report Illinois Eastern Hospital for the Insane. 1896. 8vo. 236 pages. The Blakely Printing Co., Chicago.

Twentieth Century Practice. An international encyclopedia of modern medical science by leading authorities of Europe and America. Edited by T. L. Stedman, M. D. Vol. IX. Diseases of the Digestive Organs. 1897. 8vo. 820 pages. William Wood & Co., New York.


114


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[No. 74.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Patliologry.

The VesselB and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Heney J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By P. P.

Mall, M. D.

Report In Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. GlLCHKiST, M. D., and Emmet RliroRD, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of MoUuscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report In PatliologTAn Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report In Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Laelecr, M. D. Cases of Post-febrile Insanity. By William Oslbk, M. D. Acute Tuberculosis in an Infant of Four Months. By Hahkt Todlmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report In Medicine. Tubercular Peritonitis. By William Osler, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecolosry. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 16, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By HowABD

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxosarcoma of the CHitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report In Snrgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halbted, M. D. Report in Neurology, I. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By AoonsT HocH, M. D. A Case of Cerebrospinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Patlioloery* I. Amoebic Dysentery. By William T. Councilman, M. D., and Henri A. Lafledk, M. D.


Volume III. 766 pages, with G9 plates and figures.

Report in Patliology.

Papillomatous Tumors of the Ovary. By J. Wiiitridoe Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridqe Williams, M. D. Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugata Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflcxed Uterus. By Howard A. Kelly, M. D.

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 A. L. Stavely, M. D.


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

Tabulated by A. L. Stavely, M. D. The Employment of an Artificial Retroposition of the Uterus in covering Extensive

Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdo minal Pelvic Operations. By Howard A. Kelly, M. D. Photography applied to Surgery. By A. S. Murray. Traumatic Atresia of the Vagina with Haematokolpos and Hxmatometra. By Howard

A. Kelly, M. D. Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Ansesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D. Resuscitation in Cihloroform Asphyxia. By Howard A. Kelly, M. D. One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age.

By Howard A. Kelly, M. D., and Mary Sherwood, M. D. Abdominal Operations performed in the Gynecological Department, from March 5,

1890, to December 17, 1892. By Howard A. Kelly, JI. D. Record of Deaths occurring in the Gynecological Department from June 6, 1890, to

May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osleb, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Neurology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of J/«s mitsculus; The Intrinsic Nerves of the Thyroid Gland of the Dog: The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. Halbted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. CtlLLEN, M. B. Report In Pathology. Deciduoma Malignum. By J. Whitridoe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Bluueb, M. D., Simon Flexner, M. D., Walter Reed, M. D., and U. C. Pabscns, M. D.


Volume VI. About 500 pages, many illustrations.

Report In Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods: Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol) ; Part II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part HI. — Ricin Poisoning. — Experimental Lesions induced by Acute Ricin Poisoning. 2. Experimental Lesions induced bj Chronic Ricin Poisoning; Part IV. —Hydrophobic Toxaemia. — Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies: Part V,— Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal .\pparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

CULLEN, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. Wilkins, M. D. Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. C^ullen, M. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By

William D. Booker, M. D. The Pathology of Toxalbumin Intoxications. By Simon Flexner, M. D. Tlie price of a set hound in cloth iJols. I-VI] oftlir Hospital Reports is

$30.00. Vols. I, Jl ami JII are not sold sejKiratcli/. The price of

Vols. IV, r and VI is $5.00 each.

MONOGRAPHS ON DERMATOLOGY, MALARIAL FEVERS AND TYPHOID FEVER. The following papers are reprinted from Vols. I, IV and V of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmet Rufobd,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S. Thayer, M. D., and J.

Hewetson, II. D. And A STUDY OF SOME FAT.\L CASES OF MAI^ARIA.

My Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, ^.76. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports, 1 volume of 481

pages. Price, bound in paper, $3.00. Subscriptions for the above publications may be sent to

The Johns HorKiNS Press, Baltihors, Ud.


The Johns Hopkins Hospital Bulletins are issued monthly. They arc printed by THE FRIEDENWALD CO., Baltimore. Single copies may be procured frnm Messrs. CUSHINO & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a year, may be addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. Vlll.-No. 75.]


BALTIMORE. JUNE. 1897.


[Price, 15 Cents.


COIsTTEIsTTS.


Report of a Case of Polybacterial Infection in Typhoid Fever, with especial Reference to certain Involutions exhibited by the Bacillus Typhosus. By Edward Perkins Carter, M. D., 115

A Case of Typhoid Fever in which the Typhoid Bacillus was obtained twice from the Blood during Life. By E. Bates Block, JI. D., 119

Successful Cultivation of Gonococcus in two Cases of Gonorrheal Arthritis and one of Tfenosynoviti4, with Remarks on a New Medium. By Francis R. Hagner, M. D., - - -121

A New ^sthesiometer. By Lewellys F. Barker, M. B., - 125

Edinger on " The Development of Brain Paths in the Animal Series." By C. R. Bardben, M. D.. 126


page. By Simon Flex-" - - - 128


Pseudo-Tuberculosis Hominis Streptotricha.

NER, M.D.,

Proceedings of Societies :

Hospital Medical Society, 129

Discussion of Dr. Friedenwald's paper on Congenital Motor Defects of the Eyeballs; — Congenital Facial Diplegia [Dr. Thomas]; — A Case of Acquired Paralysis of both External Recti Muscles, with Unilateral Facial Paralysis [ Dr. S. Theobald]; — Exhibition of Ophthalmological Cases: Bilateral Dacryo-adenitis, Operations for Cataract [Dr. Randolph]; — Demonstration of Florence's Iodine Test for Seminal Stains [Dr. Lewellys F. Barker].

Notes on New Books, - - 133

Books Received, 185


REPORT OF A CASE OF POLYBACTERIAL LNFECTIOX IN TYPHOID FEVER, WITH ESPECIAL REFERENCE TO CERTAIN INVOLUTIONS EXHIBITED BY THE BACILLUS TYPHOSUS.

By Edward Perkins Carter, M. D., FeUov) in Pathology. [From the Pnthologieal Laboratory of the Johns Hopkins University and Ilospital.]


The following case seems worthy of publication in view of the opportunity it afforded to study an unusual variation in morphology of the bacillus typhosus isolated from it, and because of the interesting poly-infection with bacteria which existed at autopsy.

The patient, G. C, was admitted to the Johns Hopkins Hospital on October 11, 1896, complaining of fever, weakness and loss of appetite. He had not been feeling well for three weeks, and had been unable to work for the past seven days.

Family history negative. Personal history negative. For the past four years he had led an active out-of-door life, and had up to the onset of present illness enjoyed "good health."

His illness began wnth a general feeling of weakness, which increased until on Monday, October .5th, 1896, he was unable to go to work, and complained of fever, loss of appetite and pains in the back and legs. He kept up until October 9th, and on October 11th, 1896, when admitted to the ward, he had a temperature of 102.5°, pulse 100 to the minute, and


respirations 20. E.xamination of the blood at this time and at all subsequent examinations was negative for malarial organisms. Examinations of the thorax and heart were negative. Abdomen was not distended. No tenderness and no gurgling in right iliac fossa. Several suggestive rose spots. Spleen was just palpable. Liver dulness normal. The diagnosis of typhoid fever was made and the patient put upon a strictly typhoid treatment.

I have abstracted the following notes from the history of the case, omitting the treatment as being foreign to our purpose.

October 12th, '96, at 7 a. m. The patient had a large semiliquid stool, containing some formed particles, and a considerable amount of blood fairly bright red in color. At 8.30 a. m. a second hemorrhage, rather brighter red than preceding. Both considerable in amount. Temperature 103.5°, pulse 102.

October 14th. Patient flushed, looks well. Tongue furred,


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[No. 75.


not tremulous, pulse good. Two fresh rose spots. Abdomen flat, uo distension.

October 16th, 1.40 p. m. Hemorrhage, somewhat thick tarry consistence, with some blood clots. Amount of movement about 400-500 cc. 5.30-6.30 p. m., patient had two movements like preceding, quantity same, about 400-500 cc. Pulse very running and feeble. Temperature at 8 a. m. 101.5°, pulse 124.

October 17th. This a. m. condition is distinctly better. Pulse at visit 29 to the quarter. Abdomen not distended and nowhere tender. 11.30 p. m. the patient had a stool of about 250 cc. in amount, which contained blood dark in color.

October 18th, 10 p. m. A stool, about 200 cc, containing blood, no clots. The patient's condition did not show any material change. Temperature at a. m. 102.8°, pulse 120.

October 25th, 2 p. m. The patient had a large movement, 1000 cc. Total amount of blood estimated 500 cc. Temperature at 8 p. m. 101.5°, pulse 148.

From this time, though he had no subsequent hemorrhages, the patient's condition remained critical until his death.

On October 28th he developed well marked signs of consolidation in the lower left back over a small area, and on November 1st the same signs were found in the lower right back.

November 9th. Breath sounds at left base seem almost clear. Percussion at right base impaired, breath sounds distant. Temperature at 8 a. m. 103°, pulse 124.

November 11th. This a. m. pulse 32 to the quarter. The patient passed a restless night, complaining considerably of pain in the left side. Lying on left side, skin moist. Tongue dry and tremulous. Eespirations 13 to the quarter. Profuse sweating. Eespiration on left side is enfeebled. Back not examined.

The patient's general condition gradually grew weaker and he died at 12.30 a. m., November 12th, 1896. The temperature just before death touched 105°; the pulse was 160.

The autopsy was held 34 hours after death, and the body, apart from slight post-mortem gas development, showed no other distinctive signs of decomposition.

Anatomical Diagnosis. Typhoid fever. Small number of healing ulcers in the ileum ; little glandular enlargement. Subacute spleen tumor, parenchymatous degeneration of the viscera, abscess of prostate gland, necrosis of the cricoid cartilage, pneumonia, fibrino-serous pleurisy.

Body 170 cm. long, pale, no oedema. Moderate emaciation. Rigor mortis in both extremities. Abdomen greatly distended, tympanitic and greenish in color.

The spleen weighed 210 grams. It was free from adhesions. On section moderately firm, pale grayish red in color. Malpighian bodies not prominent. Several phleboliths of the size of bird-shot in cut surface.

The small intestine was moderately distended, the mucosa opaque, containing soft fa3ces. No ulceration until within 100 cm. of the valve, where a small, clear, punched-out ulcer 1 cm. in diameter existed. The surrounding mucosa was congested. No more ulcers found for the next 50 cm., where a large group of coalescent clean ulcers with united edges occurred, which were shallow and rapidly skinning over.


These measured 3x5 cm. in extent, and the individuals composing the group were hardly larger than the above single one. The most important group of ulcers was located a hand's breadth above the valve; these numbered nine (2.5 cm. in diameter), the largest not much exceeding a silver twentyfive cent piece in size. They were perfectly clean and rapidly healing, judging from the manner in which their bases were filled up; and they appeared to be skinning over at the same time from the edges. The caecum and appendix vermiformis were free from ulceration.

The larynx on the left side shows a small aperture measuring 1 cm. in diameter, which leads into a cavity in relation to the cricoid cartilage. On dissection a cavity the size of the little finger, lined by granulation tissue, is found, and into the cavity the upper and eroded end of the cricoid cartilage projects. The upper surface gives the impression of being calcified ; it is eroded and hard. The contents of the cavity are semi-fluid pus of rather dark color.

In the right lobe of the prostate gland there existed a small abscess the size of a hazel-nut, containing creamy pus. The walls of the cavity are thin and ill-formed. No communication existed with the bladder.

The mesenteric and retroperitoneal glands were little if at all enlarged.

Bacteriological Examixation.

Cover-slip preparations made at the time of the autopsy showed from the fj^ewra large numbers of streptococci, which occurred in threads of 6-8 segments, and a few long evenly staining straight bacilli.

From the abscess in jjwstafe gland great numbers of small thin straight bacilli, which looked not unlike the bacillus of typhoid fever; also numbers of cocci, appearing chiefly in pairs (diplococci).

From the heart's Hood a number of long straight bacilli resembling closely those seen in the cover-slips from the j)leura ; also a few single cocci were seen.

Cultures.

Pleura. The agar-agar plate was studded with minute pin-point, finely granular colonies.

Microscopically these proved to be streptococci, which were identified as the streptococcus pyogenes.

Lung. The plate on the same medium resembled identically that from the pleura and contained the same microorganism in pure culture.

Larynx. The agar-agar plate showed superficially many round grayish brown pin-bead colonies, limited to one-half of surface, the remaining area being overgrown with colonies which exhibited a bluish green color. In the substance of the medium were great numbers of small, finely granular pinpoint colonies and smaller numbers of large whetstone and irregularly round colonies. This plate being so crowded, a series of plates was made, and from the third dilution the following micro-organisms were isolated and identified : streptococcus pyogenes, bacillus lactis aerogenes and bacillus pyocyaneus.

Kidney. The agar-agar plate was studded with small


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117


round dark granular colonies, much larger than the usual streptococcus colonies. In the substance of the medium there were also a number of whetstone and irregularly round colonies, and on the surface two grayish white spreading colonies and five slightly smaller grayish white more ti-anslucent ones. The small granular colonies were composed of the streptococcus pyogenes. From the other colonies two bacilli were isolated and identified as the bacillus coli communis and the bacillus typhosus. (See notes below.)

Liver. The agar-agar plate presented practically the same appearance as that from the kidney, and the same microorganisms were isolated from it.

Heart. The agar-agar plate showed two sets of colonies. The substance of the medium was studded with small finely granular colonies, and here and there a few scattered grayish white whetstone forms occurred, while on the surface there were a number of grayish white, small, fairly round and slightly elevated forms. From the small granular colonies the streptococcus pyogenes was isolated, and from the whetstone colonies in the depth and the round colonies on the surface of the medium a bacillus was isolated which was identified as the bacillus typhosus.

Mesenteric gland. The agar-agar plate showed two superficial, spreading, grayish white irregular colonies, and numbers of whetstone colonies in the substance of the medium. From the plate two bacilli were isolated and identified as the bacillus coli communis and the bacillus typhosus.

Abscess in the prostate gland. The agar-agar plate was studded with small finely granular colonies, and in addition showed a few scattered whetstone colonies in the substance, and several small, reddish brown, irregular, spreading forms on the surface of the medium. From the finely granular colonies the streptococcus pyogenes was isolated. From the superficial colonies a bacillus was isolated which was identified as the proteus vulgaris.

Spleen. The agar-agar plate from the spleen remained sterile after 48 hours in the thermostat.

The bacillus which is, however, of greatest interest in this case is that which was isolated from the heart, liver, kidney, mesenteric gland, and by Mr. Potter from the bile by means of Eisner's method, and which, though it shows great variation upon certain media, must, we think, be considered the true bacillus of Eberth.

Culturally and morphologically this bacillus was proven identical, from all of the above given sources, and our study of it has therefore been made with the cultures obtained from the kidney and bile. At the same time there was carried along with these for control a culture of an established typhoid bacillus. The bacillus isolated from the case under consideration, taken from a 24-hour growth upon agar-agar, is of medium size, straight and thin, with slightly rounded ends, taking the stain deeply and uniformly. It stains with all the ordinary aniline dyes, though most satisfactorily with gentian violet.

The Eisner plates made by Mr. Potter directly from the bile gave what has been and is considered the typical reaction for a mixture of typhoid and colon colonies. The colon colonies were larger, more coarsely granular and more numer


ous than the small, very pale, transparent and faintly granular colonies from which the typhoid bacillus was isolated in pure culture.

Upon agar-agar plates the colonies of the bacillus under study are small, grayish white in color, slightly elevated and irregularly round upon the surface of the medium, while in its substance they presented the common small whetstone or irregularly round outline. By transmitted light under low power they are of a reddish brown color and faintly granular structure. Upon gelatine plates the colonies are, after 34 hours, small, very finely granular, irregular in outline, and tend to increase in size very slightly during the second 48 hours, thus appearing as typical typhoid colonies.

Agar slant. The growth upon a moderately dry agar tube was, after 24 hours, of a slight, narrow, rail-like character along the track of the needle, being slightly elevated and of a grayish white color. On the moist agar slant it grows somewhat more profusely, covering the surface of the medium more irregularly. This was equally true of the control typhoid culture.

Bouillon at the end of 24 hours is clouded and somewhat opaque. The reaction for indol was negative. In order to establish the certainty of the negative indol reaction beyond a doubt, a culture in bouillon, together with a culture of the control typhoid, and an uninoculated tube of bouillon were placed in the thermostat for three days and then tested for indol, adding at the same time the H2S0» and NaNO: to the uninoculated tube of bouillon and watching these three carefully for a few hours, and then replacing them in the thermostat over night. When examined the following day all three tubes presented the same appearance, and it could not be said that a true indol reaction was obtained. The test for indol was made again and again without obtaining a positive reaction.

Litmus milk after 24 hours was only faintly acidulated, and reached apparently its greatest degree of acidulation, which is very slight, on the third day. At the end of a month there was no increase of acidulation, as evidenced by the pale pink color which remained quite as noted on the third day following inoculation. Coagulation of the milk did not ensue.

Upon potato the growth bears an extremely close resemblance to the control typhoid. It shows at the same time under the microscope the most remarkable involution forms, which begin to appear upon the third day after inoculation.

If the potato is strongly acid the growth after 24 hours is just visible as a delicate white membrane over the surface of the potato extending from the track of the needle. The macroscopic appearance of the growth remains unaltered, being only Just visible after thirty days, while the potato remained undiscolored.

Upon a neutral potato, on the other hand, the growth after 24 hours appears as a slightly yellowish white line along the track of the needle, spreading out somewhat at the base of the potato, being plainly visible and much more luxuriant than is ordinarily true of the bacillus of typhoid fever. After five days the potato itself becomes a very little discolored, while the growth remains unaltered after the third day. At the end of three weeks no further change was noted.


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Under the microscope this bacillus shows the greatest variation in morphology, and apparently without relation to the reaction of the potato. After the third day involution forms appear, first as long rods with unstained bulbous ends, and these are quickly followed by the most extraordinary forms, such as long threads, irregular rods with unstained poles closely resembling spores, and shorter oval forms, a picture unlike anything one finds in cultures of the true bacillus typhosus.

Glucose agar. In a deep stab this organism again agrees well with the control typhoid. After 24 hours there is a delicate, small, nail-head growth upon the surface of the medium, while along the line of puncture the growth extends downwards for one-half the distance. This appearance remains in general the same, the growth increasing very gradually until at the end of thirty days there is only a more irregular nailhead appearance upon the surface with a slight growth along the line of the needle stab, thus bearing a striking similarity to the control culture. At no time was there gas formation. Here again under the microscope the cover-glasses made after the third day show the same remarkable involution forms seen in the growth upon the potato.

In a gelatine stab there is a slight nail-head growth on the surface of the medium after 24 hours, extending along the course of the needle for a short distance as a delicate linear growth, and giving identically the same picture as that seen in the control. Liquefaction of 5 per cent, or 10 per cent, gelatine does not occur, and the growth increases very slowly, showing after three weeks a surface growth of the size of the head of a small tack. Microscopically, after the fifth day, we find involution forms in the shape of straight and slightly curved threads, longer by at least twelve times than the bacillus as it appears after 24 hours. The very unusual forms seen in the growth upon potato and sugar agar are not present.

Motility. Hanging drops made from an agar-agar culture of any age always showed great numbers of the bacilli in the field in active motion, but the greatest motility was seen when examined from agar-agar slants of from eight to ten hours' growth; at this age all the bacilli in the field appeared to be in active motion.

It decolorizes by Gram's stain.

Fermentation tubes of glucose, lactose and saccharose bouillon failed to show any development of gas after eighteen days in the thermostat.

The thermal death-point of this bacillus as established by means of Sternberg's bulbs is between 53° and 55° C. at an exposure of ten minutes.

By means of Pittfield's stain the presence of flagella can be demonstrated extending around the entire organism.

Widal's test. Upon adding from i to Jj the volume of blood serum obtained from a case of typhoid fever to a 24hours-old bouillon culture of this organism, a control typhoid bacillus culture and a culture of the bacillus coli communis according to the method of Widal, the following results were obtained :

The control culture and the culture of the organism under study gave characteristic precipitates in the same time, while that of the bacillus coli communis remained unaffected.


A number of tests for agglutination were made by the Wyatt Johnston method, using blood of known activity. The control typhoid bacillus gave immediate clumping, and the organism under study showed a similar reaction in from twenty minutes to one hour.

It is interesting to note that cultures made from potato, sugar agar and gelatine, which showed the involution forms in great numbers, always grew upon re-transplantation as the normal-sized, straight bacilli which were originally met with.

Upon plain agar-agar in bouillon and in milk the growth varied but slightly from what seemed to be the normal.

Animal Experiments.

A mouse inoculated subcutaueously with two loops from a 34-hour agar growth died in less than 48 hours.

The autopsy showed no excess of fluid in the abdominal cavity and no focal visceral lesions. The lymphatic glands were nowhere enlarged. The spleen, liver and kidneys appeared normal. At the seat of inoculation the skin was bound down by quite firm fibrinous adhesions. In the cover-slips from the seat of inoculation great numbers of bacteria were seen. Cover-slips from heart and spleen were negative. Cultures from heart and spleen remained sterile after 48 hours.

A guinea-pig inoculated with 1 cc. of a 24-hours bouillon culture intraperitoneally died after thirty days. The autopsy showed the lymphatic glands somewhat swollen and injected. No excess of fluid in abdominal cavity. Peritoneum perhaps reddened and vessels somewhat congested, but no peritonitis present. Liver, spleen and kidneys appeared normal. Coverslips from peritoneum and from all the organs negative. Cultures from same sources remained sterile.

A rabbit inoculated with 1 cc. of a 24-hours bouillon culture intravenously was still alive after two months.

We have then a bacillus which agrees culturally with the typhoid organism, which reacts to all the known tests for the true bacillus of typhoid fever, and yet which, after the third day, upon certain media, potato, sugar agar, and gelatine, shows very unusual involution forms; forms so remarkable that were it not for the evidence given by the fulfilment of every test, it would seem impossible to consider this the true bacillus of Eberth.

During the past few years a number of bacilli, found under conditions which would seem to exclude the presence of the true bacillus of typhoid fever, have been isolated and studied by Losener,* Babes,! FiillesJ and Cassedebat.§ These bacilli resembled the true typhoid organism so closely in cultural and morphological properties, with the exception of a slight variation in the organisms reported by Cassedebat and by Babes, that it has thus far been very difficult, if not impossible, to distinguish between them and the bacillus typhosus.


  • Losener, Arbeiten aus ilem Kaiserl. Gesundheitsamte, XI.

t Babes, Variabilitat und Varietiiten des Typhus-bacillus. Zeitschrift fur Hygiene, IX, 1890, p. 323.

I Fulles, Bacteriologische Untersuchung des Bodens in der Uingebung von Freiburg i. B. Zeitschrift fur Hygiene, X, 1S90, p. 225.

§ Cassedebat, Sur un bacille pseudo-typhique trouve dans les eaux de riviere. Compt. rend, de I'Academie de Paris, CX, No. 15, 1S90, p. 798.


f 1

as*, B




- \

(




(


1


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JOHNS HOPKINS HOSPITAL BULLETIN.


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These forms have therefore been designated pseudo-typhoid bacilli.

In addition to the irregular forms described by Babes as seen in growths upon agar-agar, and those in the bacillus studied by Oassedebat, Ohantemesse and Widal* have noted certain variations from the normal which appeared as longer thread-like forms upon gelatine, and as straight rods containing irregular vacuoles and unstained poles upon potato. Vilchurf further, in a study made of some 200 cultures from the organs of four tyj^hoid patients, describes variations in form, particularly on old gelatine cultures and upon potato. These occurred as vacuoles which after 73 hours took the stain and then more intensely than the rest of the organism. Aside from these irregular forms I have been unable to find in the literature any reference to such involution forms as are noted in this case.

The growth upon agar-agar in bouillon and in milk showed no variation from the normal, the irregular forms being seen only upon potato, sugar agar and gelatine, as noted above.


  • Chanteme8se et Widal, Recherches sur le bacille typhique et

I'etiologie de la fiSvre typhoide. Archives de Physiologie, I, 1887.

f Vilchur, Cultivation of Typhoid Bacillus from Organs and Evacuations of Typhoid Patients. Vrach, St. Petersburg, 1886, VII, pp. 456-458. Eef. Lancet, London, 1886, II, p. 137.


The control culture used in the study of this case did not at any time show such involution forms as the bacillus under consideration, while culturally the two organisms appeared identical.

It seems therefore unavoidable to consider that this bacillus, which was found in a patient dead of typhoid fever, being isolated from five different sources, and reacting to every test in the manner of the true bacillus of typhoid fever, is, in spite of the peculiar involutions it undergoes, no other than the bacillus typhosus.

In conclusion I wish to express my appreciation to Dr. Simon Flexner for his kindness and interest in the study of this case, and also to Dr. Gray of the Army Medical Museum, Washington, for his kindness in taking the photographs which illustrate this report.

Description of Plate.

Figs. I and II. Bacillus typhosus obtained from this case as it appears after a growth of 24 hours upon agar-agar. Zeiss II mm. apochromatic objective, No. IV projection ocular. Gentian violet staining.

Figs. Ill and IV. The same organism as it appears after a growth of two weeks upon glucose agar-agar. Same magnification. Gentian violet staining.


A CASE OF TYPHOID FEVER IN WHICH THE TYPHOID BACILLUS WAS OBTAINED TWICE

FROM THE BLOOD DURING LIFE.

By E. Bates Block, M. D., Assistant Resident Physician, The Johns Hopkins Hospital.


Evidence is strongly in favor of the fact that, at some period of the disease, the typhoid bacillus is present in the blood in nearly all patients suffering from typhoid fever, gaining entrance from time to time at the site of the intestinal lesions. It is the rule for the typhoid bacillus to be cultivated from the internal organs (spleen, mesenteric glands, etc.) after death, and sections of these organs usually show bacilli which resemble the bacillus typhosus, in clumps or masses in the capillary vessels. The early experiments of Wyssokowitsch* show that these organs are principally concerned in removing from the blood introduced bacteria. It was shown by Welch and Nuttallf in 1891 that human blood serum is capable of destroying many typhoid bacilli, and later by other observers that the blood serum from typhoid patients also possesses this power, so that the peculiar conditions which allow these organisms to live in the capillary vessels of the organs cannot, at least in the majority of cases, depend upon a simple loss of this power of the blood serum. That the invasion of the blood or organs by other micro-organisms, more particularly the streptococcus pyogenes, modifies the relation of the patient to the typhoid bacillus, has been clearly shown by VincentJ in experiments upon animals and by cultures made at autopsy

  • Zeit8chrifl fiir Hygiene, 1886.

f Verbal communication.

t Annales de I'lnst. Pasteur, 1883.


in human cases. In six out of 31 such autopsies he found the streptococcus associated with the typhoid bacillus. In one case a typhoid patient whose temperature had become normal developed a streptococcus angina, the temperature rose and on the fourth day the patient died. At autopsy the typhoid bacillus and streptococcus were obtained from the organs and the latter from the blood. The streptococcus pyogenes has also been found in association with typhoid bacillus post mortem by Flexner* in 5 out of 6 cases reported, by Wright and Stokesf in 2 out of 9 autopsies, by KleinJ in the blood, once in association with B. typhosus, by Netter, E. Fraeukel, and others. Karliuski§ has found streptoccoci in the pulmonary complications of typhoid fever in six out of nine cases, some of them being associated with the typhoid bacillus in the lungs. A similar case is reported by Flexner {op. cit.) In forty-one abscesses in typhoid cases examined by Vincent {op. cit.) the staph, pyogenes aureus was present thirty-two times, all of these patients recovering. In eight cases streptococcus alone or associated with the bacillus typhosus was met with, and of these, five died. Assuming that in these instances the typhoid bacillus was increased in virulence, it may be said that


  • Johns Hopkins Hospital Reports, Vol. V.

t Boston Med. and Surg. Jour., March-April, 1895.

tBaumgarten's Jahresb., 1894, Vol. 10.

§See Vincent, op. cit.


a similar modification of the physiological characters of the typhoid bacillus infection is produced (.Sanarelli*) by inoculating cultures together with the soluble products of the bacillus coli communis and the bacillus proteus.

The clinical history of this case presents points of interest in connection with the bacteriological investigations both before and after death.

M. Z., female, age 30, born in Poland, was admitted to Professor Osier's wards on Saturday the 4th of July, 1896. She could not speak English, so no history could be obtained. Upon admission she was restless, listless, weak, and gave evidence of shortness of breath and abdominal pain, frequently passing her hand over the abdomen. Soon after admission she became delirious. The examination of the thorax was negative. The abdomen was tender upon pressure, and resistant, especially in the splenic area. The pharynx was somewhat reddened and its vessels were injected.

On the 5th of July Dr. Thayer made the following note: Eespirations 44 to the minute, pulse 104; patient looks dull and a little confused ; the tongue has a thick pasty coat; the lungs are clear on auscultation and percussion; the heart sounds are feeble but clear; the abdomen is full, generally tympanitic, does not seem tender — it is held very tense so that palpation of the spleen is impossible. A number of small spots are seen on the abdomen, some of them apparently ecchymotic, others not unlike rose spots. There is slight cyanosis of the face and lips, which in connection with the rapidity of respiration suggests some pulmonary affection. The patient has had one liquid stool.

On the 8th of July Dr. Thayer noted further: The general condition of the patient is about the same; she is still dull, drowsy, delirious, and quite irresponsive when questioned. There is marked muscular resistance in the splenic region, and pressure here causes the patient to wince. There are no definite rose spots to-day.

The urine did not give the diazo reaction.

The temperature upon admission was 101.3°, respirations 44, and the pulse 120. Three hours later the temperature was 104.6°, and during the fourth, fifth and sixth of July ranged between 101° F. and 104.3° F., the low temperature being due to cold baths, to which she reacted well. From then on the temperature gradually declined and reached normal on the 8th of July. It remained practically normal for about 18 hours. On the following day it rose gradually, the highest point reached being 102.6°.

The respirations during her illness remained rapid and on the 9th of July became more labored, the pulse became more rapid and feeble, and the patient died at 12.45 a. m. on the 10th of July.

On the 5th of July a culture was taken from the stool of the patient, by Eisner's method, with a negative result.

On the 6th of July a hypodermic syringeful of blood was taken from a vein of the forearm with due antiseptic precautions. A few drops were allowed to fall on an agar slant, and the rest of the blood was mixed with melted gelatine and


•Ann. de I'lnst. Pasteur, 1892.


placed in a Buchner jar in the thermostat. The agar slant subsequently showed one colony, while the gelatine tube which contained a greater volume of blood showed about a dozen colonies identical in appearance. Several of these colonies were grown on the usual culture media. They did not coagulate milk, grew characteristically on Eisner's medium ; inconspicuous growth on potato with increase of moisture; did not form gas in glucose agar ; were actively motile ; did not liquefy gelatine, and morphologically resembled the typhoid bacillus.

On the 9th of July a second culture was taken by the same method. The volume of blood obtained was smaller than in the former culture and was allowed to fall on the surface of an agar slant, which 20 hours later showed one colony. Inoculations of other media from this showed the same reactions as in the previous instance. In addition these bacilli did not produce indol; grew anaerobically; did not change the color of Wurtz's medium; gave the agglutinative reaction with over 40 specimens of typhoid blood, and morphologically was identical with the bacillus obtained three days before.

A culture from the throat on the same day did not show diphtheria bacilli ; the chief organism found was the streptococcus.

I am indebted to Dr. Flexner for the privilege of making an abstract of the post-mortem examination.

The autopsy was held at 2 p. m. on the 11th of July, 37 hours after death.

Anatomical diagnosis : Typhoid fever; ulceration of small intestine; acute sjjleen tumor; swelling of the mesenteric glands; parenchymatous degeneration of the viscera; postmortem invasion of a gas-forming bacillus ; oedema of the lungs.

Body cold, has been on ice. No odor of decomposition.

The upper portion of the body shows dark spots and splotches. The face is discolored and swollen. The greatest discoloration is over the back.

Crepitation is present over the face, the neck, the upper portion of the thorax and over the back. The neck is much swollen, thick and discolored.

No oedema and no crepitation of lower extremities.

The abdomen is distended and contains gas which has a somewhat putrefactive odor. The intestines are distended, but not discolored.

The tissues about the kidneys, pancreas, caecum and the root of the mesentery are emphysematous. The mesenteric and cascal glands are enlarged, softened and reddened.

The spleen is enlarged and softened, and on section appears dark in color, almost diffluent.

The liver shows many gas bubbles under the capsule, and on section it is found to be penetrated throughout by small gas vesicles, and the blood which escapes from the cut ends of the portal veins is frothy. The organ is pale, homogeneous, and cloudy yellow in color.

Both kidneys are emphysematous, the capsules adherent, the cortex increased, and the stria? coarse.

The duodenum shows many gas cysts. The small intestine shows swollen patches of Peyer; lower down the patches exhibit small erosions. As the valve is approached the enlarge


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ment of the patches increases, as does the extent of erosion. Occasionally these patches show hemorrhagic infiltration. At the valve nearly the whole of the intestine is involved in deep ulceration which presents a sloughy and necrotic appearance and is nearly black from imbibition of blood.

The lungs are deep in color, crepitate throughout, and almost sink in water. The cut surface is smooth and dark. The bronchi are dark in color from imbibed blood. The blood in the vessels is frothy. The right side of the heart is enormously distended. On incision there is escape of gas and collapse. The intima of the vessels, and endocardium, are deeply blood stained.

In the right upper angle of the cavity of the uterus is a portion of placenta the size of a walnut, apparently the remains of a recent abortion. It is oval in shape, firmly attached, dark in color, porous in consistence, and has a deep red color. The mucosa is congested.

Cover-slips from the heart's blood, liver, spleen and intestinal ulcer showed, along with other bacterial forms, a large capsulated bacillus resembling closely the bacillus aerogenes capsulatus. These were not seen upon cover-slips from the bile and placenta. Anaerobic cultures were taken from all of the organs, but the large bacillus failed to grow.

Cultures upon agar plates yielded the following results: Bacillus typhosus in placenta, spleen, liver and kidney. Bacillus coli communis in the kidney and heart's blood. Bacillus pyocyaueus in the heart's blood. Bacillus proteus in the bile.

Some of the appearances found at the autopsy must be regarded as due to post-mortem changes, so that the invasion of the bacillus coli communis and the bacillus proteus after death cannot be entirely excluded. It is not improbable, however, that they may have been present in the orgaiis or body fluids during life. The bacillus pyocyaneus is not a common post-mortem invader.

In reading over the available literature I find that the typhoid bacillus has been obtained during life from the blood of patients suffering from typhoid fever by three other writers. Thiemich* found it once in blood taken from a vein


' Baumgarten's Jahresbericht, Vol. 10, 1894, p. 266.


of the forearm. Ettlinger* obtained it twice by the same method, and Stern twice.f

Other writers report a negative result. NeuhausJ failed in twelve cases from blood taken from a vein of the forearm, and twenty-four cultures§ from blood obtained by pricking the skin of the forearm; Frilnkel and Simmonds|| in sis cases. Ettlinger** reports eight negative results with blood taken from the forearm, and Klein ten.|f Failvires are also reported by Gaffky, Riitimeyer, Chantemesse and Widal, v. Jaksch, and Vaquez.

In six other cases I failed to obtain the typhoid bacillus, although a syringeful (1.5 cc.) of blood was employed in each instance.

The typhoid bacillus has been obtained from the blood after death by several observers: Viucent,|| Friinkel and Simmonds,§§ Flexner,|||| Klein,*** and by Wright and Stokes.fft

Heretofore not much importance has been attached to the work of Letzerich,JII Almquist,m Maragliano,||| Riitimeyer,§§§ Pasquale,§§§ Guarnierl,§§§ and Karliuski,§§§ because their examinations were made at a time when the differentiation of the typhoid bacillus from other micro-organisms closely resembling it in morphological and biological characters, was not so clearly understood as it is at present. However, it is probable now, that since definite proofs exist of the not very infrequent occurrence of the bacillus typhosus in the blood, either before or after death, their work may come to have more significance.


  • Wirtz, Precis de Bacteriologie Clinique.

■fCentralb. f. innere Med. 1896, No. 49, p. 1249.

I See Wurtz.

§ Berliner klin. Wochenschr., No. 6, 1886.

II Sternberg, Text-book of Bacteriology, p. 352.

    • Loc. cit.

■H-Baumgarten, Vol. 10, 1894, p. 266.

XI Ann. d. I'lnst. Pastesr, 1893 ; Le Mercredi medical, 17 fev. 1892.

§§ Sternberg, Text-book of Bacteriology, 1896, p. 352.

ill Op. cit.

      • Baumgarten, 1894, Vol. 10.

tttOp. cit.

ttl Sternberg, op. cit. §§§See Flexner, op. cit.


SUCCESSFUL CULTIVATION OF GONOCOCCUS IN TWO CASES OF GONORRHEAL ARTHRITIS AND ONE OF TiENOSYNOVITIS, WITH REMARKS ON A NEW MEDIUM.

By Francis R. Hagner, M. D., Assistant Resident Surgeon, Johns Hopkins Hospital.


The more successful attempts to cultivate the gonococcus from pathological conditions other than urethritis and conjunctivitis, have widened our view concerning the part played by this organism in human pathology.

Even now it would take much space to enumerate all the different lesions and parts of the body in which this organism has been found. The gonococcus, as is well known, cannot be cultivated with the facility of the other pyogenic cocci, and it has for this reason not lent itself so readily as an aid to diagnosis in obscure cases, unless perchance it could be found in


cover-slips, where its peculiar form and definite staining reaction might suflBce for its identification.

Greater experience, on the other hand, has shown that, although this organism does not grow at all, or at least most feebly and unsatisfactorily, upon the ordinary culture media, its choice of substance is still not a small one.

Since Steinschneider's observation of the great value of urine in the composition of a culture medium for the gonococcus, no really easy practicable method of preparing a medium containing this fluid has been devised.


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[No. 75.


We offer iu the accompanying paper a simple method which, in the limited number of cases at our disposal, has proven successful.

It is in part my object in presenting these cases to draw attention to the ease with which, by the use of this medium, the gonococcus may be cultivated.

I must state that the value of the medium was further tested and proven by cultivating this micro-organism from urethral piis. The cases themselves are of interest from their clinical aspects, and as illustrating the good results which surgical interference gives when undertaken in time.

The possibility of making a positive diagnosis before opening the infected joint enhances the likelihood of good which may be confidently expected from these measures.

No question is likely to arise as to the identity of the cocci isolated in these cases, even in view of the fact that in one case the organism did not completely decolorize when treated according to Gram's method.

The later writers on the subject, among whom I shall only mention Caplewski,* concede great difference in the behavior of cocci from different sources.

Most samples of gonococci are quickly and readily decolorized; some few are more refractory and may retain the stain in part. On the other hand, the ordinary pyogenic cocci which resist Gram's method sometimes become decolorized.

No small part in this procedure is played by the composition of the stain and decolorizing agents.

But when all the facts are gathered, namely, the source of the organisms, their morphological properties, their diflBculty of culture, and slight viability, together with their staining reaction, no doubt is likely to be entertained concerning their nature.

Case I.

B. B., set. 21, female, colored. Domestic. Admitted December 5, 1896.

Previous History. Patient has never been very healthy. One year ago she had an attack of rheumatism; at this time the right knee was swollen and painful. The jjatient was confined to bed for one month, and has never had any trouble with the joint since. There was no history of any vaginal discharge at this time.

Present Illness. Patient acknowledges exposure within the last month. Has had vaginal discharge for three weeks. Six days before entrance to the hospital she noticed pain and swelling of the left knee. Pain more marked at night and increased by motion.

Examination. The patient is a rather poorly nourished, unintelligent woman, with a slight blowing murmur over the apex of the heart, transmitted to axilla. The joint is quite tense, painful on palpation and motion. Patella floats. There is marked induration and thickening of the peri-articular tissues, which are boggy. Distinct fluctuation over the joint. A purulent discharge observed to be present in vagina and urethra. The examination of cover-slips was negative for typical gonococcus-like organisms.


  • Hygienische Rundschau, Vol. 6, No. 21, p. 1029.


December 5th. Knee aspirated with sterile syringe and a straw-colored fluid obtained; this showed under the microscope a great many polymorphonuclear leucocytes, and a few large diplococci which were not contained in the pus cells. Cultures made on agar-agar, gelatin, potato and bouillon were negative after forty-eight hours in the thermostat. Cultures made at the same time on albuminous urine agar in twentyfour hours showed no perceptible growth, but at the end of forty-eight hours in the thermostat about a dozen isolated colonies, a little larger than ordinary streptococcus colonies, elevated above the surface of the medium, presenting an opaque white color, but still translucent, were easily seen.

Cover-slips were made, staiued with Sterling's gentian violet, mounted in water. The examination showed diplococci morphologically identical with the gonococcus. The same specimens were then stained by Gram's method and almost completely decolorized, a faint outline still being visible here and there. The ordinary media (mentioned previously) were inoculated from the cultures with negative results; but another albuminous urine agar tube, inoculated, gave a similar growth to the first after forty-eight hours in the thermostat, and this showed the same morphological characteristics.

Another generation, third in succession, was obtained on the albuminous urine agar medium; this one was feebler than the preceding ones, and no further growth was obtainable.

December 8lh. Knee again aspirated, the fluid giving the same growth when inoculated on the albuminous urine agar tube.

The same negative results as described previously were obtained on the ordinary media. The growth mentioned was carried through three generations, but again would not grow on the fourth transplantation.

December 17th. The knee joint was opened and cultures taken, two tubes of the albuminous urine agar being inoculated. One of these became contaminated ; in the other the growth was very slight and did not survive for a second transplantation.

The following is a brief description of the mode of preparation of the albuminous urine agar, which was prepared by Dr. Hugh Young and myself.

Acid urine containing 0.05 albumen or more should be collected and allowed to stand for twenty-four hours, no effort being made to prevent decomposition. The urine is boiled until a large albuminous precipitate is formed ; it is filtered through paper, when the resulting fluid will be clear. The filtered urine is boiled, and agar-agar, peptone, beef extract and sodium chloride are added in the same proportion as making ordinary agar.

The other steps are the same as in making ordinary agar, except that filtered albuminous urine instead of water is used throughout the preparation of the medium. It is important to see that the medium before being placed in tubes has a neutral or slightly acid reaction.

The advantages of using albuminous urine are, first, that iu such urine albumens are always present, which are not coagulated by heat, and second, the albumen that is coagulated acts as a clarifying agent in the removal of the salts that usually cause the cloudiness of urine agar-agar as prepared by


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mixing the urine agar separately and sterilizing by discontinuous heating below the point of coagulation. It is important to have the medium very moist when inoculated.

The operation consisted of opening and irrigating with bichloride of mercury 1 to 1000, followed by salt solution, an Esmarch bandage being applied above the joint to prevent absorption of the bichloride solution.

The wound was approximated with subcutaneous silver wire sutures, silver foil dressing applied, and the leg put up in plaster. Of course very strict cleanliness is necessary in these operations — in all cases the operator and assistants wearing rubber gloves. The wound healed perprimani.

At the time of operation the subcutaneous tissues were found very edematous and thickened, and minute hemorrhagic areas were seen in the tissues near the joint. The fluid within the joint was serous in character, although flakes of fibrin were contained in it. The synovial membrane was thickened and its surface covered with hemorrhagic material that in places had a plush-like appearance, having lost its gloss. At the junctions of the cartilages and synovial membrane there were a number of tessellated, very vascular fringes of fibrinous material 3 to 5 mm. in length.

The cartilages showed no change.

The patient is at present more comfortable, but has not entirely recovered.

Case II.

A. D., female, fet. 20 years, colored, domestic. Admitted August 25, 1895.

No history of rheumatism.

Has had vaginal discharge for two weeks. (Patient acknowledges exposure several days before the discharge was noted.)

Three days before entrance left knee joint became painful and swollen, pain being more marked at night; fever was present, the highest temperature recorded being 103° F.

Examination. Large, well nourished woman.

Left knee slightly flexed, and warmer than adjacent parts. Slight fluctuation on inner side of patella ; movement of the affected joint caused great pain.

The peri-articular tissues were indurated and boggy.

There was a purulent discharge from the vagina and urethra that contained diplococci. These were in a manner suggestive of the gonococcus and occurred within the pus cells; they completely decolorized when stained according to Gram's method.

The operation was done on the fifth day of the disease, and consisted in the application of an Esmarch bandage, incision of the joint, irrigation with 1 to 1000 bichloride of mercury followed by salt solution, and closure of wound with silver wire. Silver foil dressing and plaster cast applied.

Patient made good recovery.

The examination of joint at time of operation showed the peri-articular tissues to be in an cedematous and hemorrhagic condition.

The joint contained about 25 cc. of blood-stained fluid in which floated small pieces of a fibrinous material.

The synovial membrane was roughened, thickened and had the same appearance described in the preceding case.


Larger tessellated masses of fibrin adhered to synovial membrane wherever it came in contact with the cartilage.

Bacteriological Examination.

The fluid for culture was removed from the joint with a sterile Volkman spoon, and placed in sterile test tube. A small quantity of blood was obtained by allowing a stream from a small artery to spurt into a sterile test tube.

The tube containing the blood was allowed to stand for two hours, during which time the serum had separated from the clot and could be pipetted off. An ordinary agar tube was melted and cooled to 46° C, so as to prevent the blood serum from coagulating when added. About 5 cc. of the human blood serum was added, making the proportion one-third human blood serum and two-thirds nutrient agar-agar; the resulting medium was perfectly clear. The fluid medium was then mixed thoroughly, and inoculated with three loops of fluid obtained from the joint, great care being taken not to add the fluid until the medium was observed to be on the point of solidifying, so as to prevent all chances of destruction of the organism by heat.

The inoculated medium was poured into a Petri's dish and placed in thermostat at 37° C. No growth was visible at the end of the first twenty-four hours, but at the expiration of forty-eight hours five or six small colonies could be seen. These were isolated and about the size of the ordinary streptococcus colonies, but they were more elevated when they appeared on the surface of the medium, and of a more opaque white color; they were, however, slightly translucent.

Cover-slips prepared from such a colony and stained with Sterling's gentian violet, mounted in water, showed numerous diplococci somewhat larger than the ordinary pyogenic cocci, composed of two hemispheres separated by a narrow unstained interval ; a few tetrad forms were also seen. The same preparation treated by Gram's method was completely decolorized.

Agar-agar, bouillon, potato, gelatin, and glycerine-agar were then inoculated from one of the colonies.

At the same time another culture was made on the serum agar. No growth could be seen after forty-eight hours on any of the tubes except the one containing the human serum agar, and on this a growth similar in appearance to the ones described before, consisting of cocci with the same morphological properties, was found; further transplantation was not successful on this medium.

As no perceptible growth occurred on any of the ordinary cultural media, and cover-slips taken from their surfaces were negative, the conclusion that the organism was the gonococcus was considered justified.

It is interesting to note that although numerous coverslips were made from the fluid at the time of operation, and numbers of polymorphonuclear leucocytes were found, no micro-organisms could be discovered.

Case III. A. P., male, white, single, 39 years. Admitted May 20, 1896.

Denied any venereal disease. (Very questionable.) Patient felt, without any premonitory symptoms, great pain


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in the left aukle joint, and at the same time noticed that there was considerable swelling and redness of the skin over the joint.

The pain was more marked at night, and increased with movement.

The condition mentioned gradually grew worse until the twenty-fourth day after the beginning of the disease, when patient was transferred to the surgical ward.

Examination. Patient was a well nourished man. Temperature on entrance 100° F. There was a fluctuating swelling extending from the juncture of middle and lower third of tibia, following the sheaths of extensor muscles, to a point on the dorsum of foot 3 cm. below the ankle joint.

May '21st, Operation. Same operation as described previously.

Incision of abscess and excision of fibrinous material from tendon sheaths. Irrigation of bichloride of mercury 1 to 1000, wounds closed with silver wire and dressed with silver foil, and leg put up in plaster. Patieut made good recovery in three weeks, wound healing per prima?/!. On incision the subcutaneous tissues were oedematous and slightly hemorrhagic. The tendon sheaths were thickened and covered with hemorrhagic fibrinous material.

The pus was confined principally to the sheaths of tibialis anticus and extensor proprius poUicis, chiefly about the annular ligament, but followed the pollicis to a distance of 3 cm. below. The sheaths were opened and about 100 cc. of bloodstained fluid escaped, which was placed by means of a Volkman spoon in a sterile test tube.

The internal portions of the sheaths were covered with a hemorrhagic fibrinous material and some granulation tissue.

I am indebted to Dr. Flexner for the privilege of reporting his successful cultivation of the gonococcus in this case. The pus collected at operation in a sterile manner was sent to the Pathological Laboratory.

Cover-slips when stained with Sterling's gentian violet showed polymorphonuclear leucocytes filled with diplococci morphologically resembling the gonococcus; a few of the organisms seen were extra-cellular.

When stained according to Gram's method the organisms were completely decolorized. Inoculations of the pus were made on the mixture of Steinschneider,* on a mixture composed of human ascitic fluid and agar-agar,t on a mixture of human blood serum and uriue,J on an infusion of pig-fcetuses and nutrient agar,§ and also upon ordinary agar slants. The


  • Steinschneider'8 medium consists of a mixture of bullock's

serum, urine, and agar-agar.

tThe mixture of ascitic fluid i and agar-agar J, which after being placed in tubes is sterilized and slanted. An albuminous flaky precipitate collects at the bottom of the medium, leaving surface clear.

t Human blood serum and urine medium is composed of J urine, f human blood serum sterilized in autoclave at 220° F. (Human serum derived from placenta.)

§ Preparation of pig-failvt a<]ar : Fresh pig-foetuses not exceeding 5 cm. in length separated from placenta and membranes are minced in a sausage machine. An equal volume of distilled water is added to the finely divided foetuses, and after thoroughly stirring, the mixture is allowed to macerate in a cool place for from


cultures were placed in a thermostat at 37° C, and at end of twenty-four hours a scarcely perceptible growth was found on all the inoculated tubes except the agar slants, which last remained sterile, whereas the growth on the other tubes increased somewhat during the next twenty-four hours.

The appearance of the growth was the same as that described in previous cases.

Growth on pig-fcBtus agar was more abundant and apparently more vigorous than on the other media.

Cover-slips from the cultures showed the same diplococcus as was found in the pus, and it became decolorized completely by Gram's method.

Transplantations at intervals of forty-eight hours were made on pig-foetus medium mentioned and growth obtained for four generations, but from the fifth inoculation no growth resulted.

It is interesting to note that the condition of synovial membranes and peri-articular tissues in these cases was practically the same, namely subcutaneous oedema, thickening and induration of peri-articular tissues, with small hemorrhagic areas.

The synovial membrane was thickened, very hemorrhagic and had the appearance of plush, having lost the glossy condition.

The fringe-like pieces of fibrin were very hemorrhagic. In neither case was the cartilaginous portion of joint affected.


six to twelve hours. The fluid is then freed from contamination by filtration through a Chamberland filter under a pressure of 150 to 200 lbs.

Two per cent, sterilized nutrient agar is then melted and cooled to 40° C. and to it J of its volume of the infusion of foetuses is added. The tubes are then slanted.


NOTICE.

All inquiries concerning the admission of free, part pay, or private patients to the Johns Hopkins Hospital 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 $5.00 per week has been established. The Superintendent has authority to modify these terms to meet the necessity of urgent cases.

The Hospital is designed for cases of acute disease. Cases of chronic disease 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 $20.00 to $35.00 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 specialist, 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.

One week's board is payable when a patient is admitted.


June, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


J^ NEW ^ESTHESIOMETER.

By Lewellts F. Barkee, M. B. {Exhibited to the Johns Hopkins Hospital Medical Society, January 18th, 1897.]


I exhibited at this Society some time ago the test hairs employed by Professor von Frey in studying pain and pressure sense. These consisted, it may be recalled, of short wooden handles of suitable length, to which finer and coarser hairs were fastened at one end at right angles with sealing wax. The most suitable form is perhaps a four-sided wooden handle measuring 4 mm. on each side and 80 mm. in length. Hairs of different strength are obtained from the scalp of men, women and children ; hairs from the beard, from the horse's tail and hog bristles are also of service where stronger stimuli are required. The advantage of these test hairs consisted, it will be remembei'ed, (1) in the very small surface of skin acted upon, and (2) in the possibility of grading accurately the intensity of the stimulus applied. In order to test the stimulus- value of the hair, its area in cross section must be determined, as well as the weight which can be lifted by the hair when it is pressed with its cross section against one of the scale pans of a delicate balance. I described on the former occasion the methods of determining these two constants and shall not now repeat the details. Suffice it to say that with time and patience a set of such test hairs can be prepared varying in stimulus-value from 0.1 gr./mm^ to 300 gr./nim', though, as Professor von Frey says, the jireparation of them is " nicht jedermanns Sache."

A


B



FlQ. 1.

The form of the hair and its mode of action are shown in Fig. 1. A represents the test hair when it is placed upon the skin at the point F, though as yet no pressure has been exerted. In B the handle is nearer the skin, through pressure made parallel to the surface of the skin, and the hair is bent into an S-shaped curve, the turning point of which is at W. If W is perpendicularly above the point F, then the hair exerts exclusively an influence of pressure upon the skin ; but if W be directed to one side, there arises along with the pressure a "shoving" component. The latter appears, as one finds on bending the hair, as soon as it begins to twist out of one plane; that is, a space-curve arises instead of the plane-curves.


The set of hairs which I pass around were prepared under Professor von Frey's direction in Leipzig in the spring of 1895. I have tested them at intervals since that time and find that they have undergone very little variation. For accurate testing of pressure and pain sense some such delicate testing mechanism is indispensable. Such hairs, however, are not in the market, and I fear if one wished a set of them he would have to prepare them for himself.

Kecently, however. Prof, von Frey, // with the aid of the mechanician Zimmermann, has prepared a simple instrument which, for purposes of clinical examination at least, will take the place of the set of test hairs. This Ksthesiometer, which depends upon the same principle as that involved in the construction of the test hairs, has the advantage that with a single hair one can obtain a large series of pressurevalues at will. It consists of a long hair pushed through a capillary tube of very narrow lumen, much like that of a thermometer tube; the hair can be shoved through the lumen easily, but on pressure only the part of the ' hair outside the capillary tube can bend, and the force exerted is always g greater the less the amount of hair outside the tube, and feebler the greater the length of hair not inside the capillary tube. In Fig. 2 the mechanism is shown, though the sample which I pass around has some improvements not illustrated in the figure. The capillary tube consists of a brass tube, S, of very narrow bore, over which a sheath H glides with slight friction. In the axis of the siieath, and of the same length as this, runs a wire, which fits in the bore of the tube S, and at the end of which the test hair is fastened. If the sheath be shoved entirely over the scale the hair projects in its greatest length, and has accordingly only very slight force. On the other hand, if the sheath be drawn back as far as possible the greatest part of thf iiair


K7


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[No. 75.


disappears within the bore, and the short still projecting part is capable of exercising very considerable pressure force. By means of a screw the sheath can be held iirmly in any position corresponding to a test hair of any desired length. There is a millimetre scale on the tube, by the help of which a given length of test hair can always be found again, together with a protecting tube for the free end of the hair to complete the instrument.

The testing of the hair for its pressure values at different lengths can be carried out with the aid of a delicate balance, and if one makes determinations for every fifth or tenth line of the millimetre scale he can easily calculate the values for the intervening lines. With this instrument it is easy to pass from very low pressure values, even below the threshold for the most delicate pressure points, to pressure values above the pain threshold in parts of the body where the pain threshold is high.

The value of this instrument was demonsitrated with Dr.


Gushing in the ward the other day. In a case in which ordinary slight stimuli appeared to call forth pain constantly, the idea had arisen that pressure sense was absent, the pain sense being very much exaggerated. It was easy with this instrument to show that the pressure sense was not abolished, though the threshold for pain was almost at the same level as the threshold for touch. With care, however, the pressure points could easily be made out. The significance of careful examinations in such cases is obvious, for it would be easy for the clinician to make the statement that tactile sense was destroyed in a given case in which in reality it was unaffected or but little affected. If such a case should come to autopsy, one might be entirely misled in interpreting the lesions found.

The sesthesiometer is not expensive, costing I believe five marks, when purchased from E. Zimmermaun of Leipzig. I cannot recommend it too highly for use in clinical examinations.


EDINGER ON "THE DEVELOPMENT OF BRAIN PATHS IN THE ANIMAL SERIES."*

[Abstract of a Keport made by C. K. Bardeen, M. D., before the Journal Club of the Johns Hopkins Hospital.]


In this address Edinger speaks in a most interesting way of the value and possibilities of a comparative psychology based on careful biological and morphological study. He himself, he says, was led to undertake this line of research by the knowledge that the lowest vertebrates have no cerebral cortex. In man and in the higher vertebrates the finer conscious activities take place in this part of the brain, and in the ascending vertebrate series there is a gradual development of the cerebral cortex up to man. " Indeed, in man," says Edinger, " the evolution of the brain cortex is still under way." The interesting questions arose. What nervous activities are possible in animals without a cerebral cortex ? and What nervous and mental activities have been added as the cortex has been evolved in the animal series ? The solution of these questions involved the broader task of studying the finer structure of the nervous system of the lower vertebrates. It was found on investigation that those parts of the brain which, as opposed to the cortex, are designated as the " lower parts " are essentially similar in all vertebrates. The spinal cord and medulla of the fish and of man do not differ fundamentally.

"So far as we know to-day," says Edinger, "we may ascribe to similar structure similar function." If this be true we may hope by careful study of the morphology of the nervous system to have opened up new points of view for physiology and psychology. If to the spinal cord, for example, the functions


  • " Die Eatwickelung der Gehirnbahnen in der Thiereihe," delivered before the medical section of the " Gesellschatt deutschcr

Naturforscher und Aerzte," in Frankfurt a. M., Sept. 23, 1896, and reported in the Deutsche medicinische Woehenschrift, Sept. 24, 1896, Vol. XXII, No. 39. [Prof. L Edinger of FrankCort is well known in America as the author of a very lucid text-book on the structure of the brain, "Der Bau des Gehirne." He is perhaps the foremost worker in the line of research of which he speaks in his address.]


of which are well known, comparative anatomical study shows that other structures are added little by little, we may suppose corresponding additions in functional capacity.

Edinger lays special stress on the need of care in forming our conceptions of the operations of the nervous system of the simpler animals. We must carefully rid ourselves of all preconceived notions of perception and desire as the necessary accompaniments of complex reactions to stimuli. We have, he says, no grounds for belief that such states of consciousness arise outside the higher centres of the cerebrum. We have no right to assume that in the lower animals the simpler nervous system performs functions like those performed by the higher centres of the nervous system in the higher vertebrates. " I trust I may be able to prove," says Edinger, " that the latter assumption, so commonly made, cannot be maintained."

To show how easily one might falsely attribute a conscious origin to complex movements, two or three examples are given from the invertebrate kingdom. Loeb's interesting experiments with the actinia are quoted. If a bit of fish be placed on the tentacle ring of one of these animals the tentacles close in and force the food into the mouth between the tentacles. But a piece of white paper put in the same situation is left undisturbed. This at first sight might seem a voluntary choice between the food and the paper, involving a conscious perception of taste. But if the mouth be destroyed and the bit of fish be again put on the tentacle ring the actiniau will double itself up trying vainly to force the morsel into the closed mouth. The definite activity caused by the meat is, roughly speaking, a direct reaction of the tissues to a chemical stimulus. The actiniau has no very definite nervous .system, though certain of its cells are taken to represent nerve

rrlLs.

Hdiu^er also refers to the recent studies on the nervous


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system of tlie earth-worm. Thanks to the work of Loeb aud Friedlaender on the living earth-worm, and that of Retzius aad von Lenhossek on the morphology of its nervous system, the task of comparing its structure with its psycho-physiological activity has been greatly lightened. If the earth-worm be cut into pieces not too short, and one of the pieces is stimulated to move, it will continue creeping. The movement is produced as follows: from large epithelial cells in the external skin the earth-worm's sensory fibres pass into the central ganglia situated in the ventral band ; here the process divides into at least two parts. These lie in contact with the dendrites of large ganglion cells lying in this ganglion and in those immediately adjoining. These large cells send processes to the muscles. Each ganglion sends motor fibres, not only to the muscles of the segment within which it lies, but also to those of the neighboring segments. Some of the fibres cross the median line. A third set of cells have processes which run up and down the veutral band connecting different ganglia. Thus a sensory impulse started in a large epithelial cell is carried to the neighboring ganglion. Here the motor and associative cells are called into activity, and the muscles in the vicinity of the segment whose surface has been stimulated contract. This throws increased tension on the surface of the neighboring segments and they in turn are stimulated to contraction. A contraction wave is thus started along the worm, called forth by simple reflex action. This scheme is not diagramatic; it is based on the actual observations of trained observers.

The mechanism which controls intestinal contraction in the higher animals is very similar.

The nervous mechanism found in the vertebrate spinal cord is fundamentally the same. Here again we find motor cells sending processes to the muscles; here again processes from sensory cells terminating in gray matter ; here ag.ain, but in a far more developed degree, association neurones. That the spinal cord is capable, unassisted by the higher centres, of carrying out very complex movements is shown by the complex activity of the frog deprived of a cerebrum, the jumping of the brainless rabbit and the swimming of the brainless


The morphological structure on which the functions of the spinal cord depend has now been fairly well determined. Beside the factors already mentioned there enter into its structure paths connecting it with the brain. In the fish paths connect mid-brain and cerebellum with the spinal cord. Connections between the cerebrum and the spinal cord first appear in mammals. " The direct influence of the cerebrum on the activities controlled by the spinal cord varies, therefore, according to the class of animal, and it does not even exist among the lower vertebrates." The pyramidal tract is not found in birds.

The medulla, while, like the cord, serving as a primary centre for the reception of sensory and the origin of motor fibres, has a much more highly developed associative mechanism than the cord. Yet the development of these paths of association varies greatly in different animals. In the carps and many other fishes it has a more complex development than in man. The complexity of development of the medulla depends chiefly


on the uses to which the cranial nerves are put. The terminal area of the fifth nerve, so well developed in the sensitive-faced mammals, is but slightly developed in the snakes, but the motor area of the fifth nerve in snakes is relatively more developed than in the mammals, owing to the snake's powerful jaw muscles.

The cerebellum varies greatly in development, even among the fishes. Those that swim actively have it more highly developed than the mud-seeking varieties. Birds being animals of delicate sense of balance have it well developed. In snakes it is very rudimentary. Whatever the functions of the cerebellum may be, this organ is well developed in all animals executing carefully poised movements. The hemispheres of the cerebellum first appear in the mammals.

The connections of the cerebellum with other parts of the central nervous system are interesting. The pons fibres first appear in the mammals, and it is probable that the olivary paths do not occur in the lower forms. On the other hand the connections with the spinal cord through the corpus restiforme and with the thalamus through the suj)erior cerebellar peduncle are primordially old. The latter are more highly developed in fishes than in man.

Next to the spinal cord the mid-brain is that part of the central nervous system most alike in all vertebrates. It is the primary terminus for the optic fibres, and in it end a large part of the secondary sensory fibres transmitting impulses from the other sense organs. It is the great centre for the association of sensory impulses in the animals without a well developed cerebrum.

The cerebrum in all vertebrates is composed of olfactory apparatus, basal ganglia and cortex.

The olfactory region varies greatly in development. In reptiles and in fishes it makes up half the brain mass. In birds it is scarcely to be traced.

The corpus striatum, which lies just behind the olfactory apparatus, appears developed throughout the vertebrates. It plays a chief part in connecting thalamus and fore-brain, but in large part its functions are ill understood. The optic thalamus is likewise complexly developed throughout the vertebrates. The cortex stands in marked contrast to the lower parts of the central nervous system which are so much alike among all the vertebrates. In fishes the cortex consists of a thin epithelial plate. In the amphibia it contains a simple nervous apparatus. In reptiles a true cortex appears for the first time.

Within the last twenty-five years it has been definitely shown that the cortex performs the highest functions of the nervous system. On the existence of a normal cortex depend all those functions which may be learned, almost all which are carried out by memory pictures, and, above all, those complex conscious processes designated "associative." The silver stain has shown into what a complexity of relations each nerve cell is brought by its processes. From the reptiles to man this associative complexity increases.

It seems probable that various sensory areas in the cortex have been added as the need has arisen for more highly developed associative processes connected with the special senses. The earliest cortical relations are with the sense of smell


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only. Reptiles, we may assume, differ from fishes in that they can "retain their smell impressions, associate them and choose." For the reptile the cortex is an olfactory centre and out little more.

" This first inheritance of the cortex, the olfactory centre, remains throughout the entire series ; in birds alone is it somewhat uncertain. There is no difficulty in following the cortex of the reptiles into the Amnion's horu and the uncinate gyrus of mammals and mau."

But in the course of evolutionary development other brain centres have been added to this ; the cortex has been built up piece by piece. Unfortunately most of the steps are still uncertain. Something is, however, known of the optic paths. In fishes the optic nerve ends in the mid-brain. And so too in man at birth the only functional fibres end there. The babe is not blind, but it has no association centres for sight impressions. During the second mouth of life paths are developed from mid-brain to occipital lobe, the cortical sightcentre is called into activity, and association paths are formed between it and the rest of the cortex. The child only then begins to perceive what it sees.

It is because the fish has no cortical centre for sight that it can be hooked. To a similar reason is due the fact that reptiles and amphibia often go hungry when they do not smell their prey and it does not move. Snakes which do not eat dead mice will seize and devour, without a trace of dislike, dead mice artificially made to move.

Birds have a well marked cortical area for sight, and hence they exhibit many phenomena which indicate reason and memory founded on sight impressions.

It is clear, however, that in the lower animals many functions are performed without the influence or control of a cortex, and the question naturally arises as to the real nature of


the functions of the lower centres. It is well known that man and the higher mammals are more injured in normal activity by loss of the cortex than are the lower vertebrates ; that the cortex becomes indispensable iu proportion as it becomes well developed and is brought into close association with the lower centres. This has been shown by the study of the diseased human brain and by experiments on animals. But nature offers us animals with no cortices and with cortices variously developed along special lines. We have here a beautiful opportunity to study the functions of the cortex in the animal economy. Most interesting points of view might be obtained by excitation of the olfactory nerves of fishes which have no cortical centres, and of snakes which have cortical centres for smell ; or by comparing the effects of visible objects on snakes which have no developed associative centre for sight, and on birds which have them well developed.

And this same sort of study carried to man will also prove productive. The great man need not necessarily have a heavier brain than the average man, but we should expect that part of his brain which he had occasion to use to be better developed than the average. The great painter should have a well developed occipital lobe ; the great musician a well developed temporal lobe. Gambetta's brain was not above the average in size and weight, but the speech area was very greatly developed. For the present, Edinger points out, we may willingly refrain from speculating about convolution anomalies and criminal types. More fruitful fields of investigation are offered the scientist. The field of comparative psycho-physiology and comparative morphology gives every promise of being most fertile. One thing seems sure, " there is no boundary to be established between the conscious activities of the lowest and those of the highest vertebrates."


PSEUDO-TUBERCULOSIS HOMINIS STREPTOTRICHA.

[A PRELIMINARY NOTE.]

Bt Simon Flexnee, M.D.

[From the Pathological Laboratory of the Johns Hopkins University and Hotpital.'\


At the meeting of the Johns Hopkins Hospital Medical Society held on October 19th, 1896, 1 presented specimens from the lungs and peritoneum of a man who had succumbed to a disease characterized by symptoms which resembled those of phthisis pulmonum, but in the lesions of which, instead of the bacillus tuberculosis, another and probably entirely distinct microorganism was discovered, for which I have proposed the name of streptothrix pseudo-tuberculosa. As the publication of the full report of the case and the complete description of the micro-organism has been somewhat delayed, a brief outline of the case may be of interest at the present time.

The patient was a male, colored, aged 70 years, in whom extensive consolidation was made out in both lungs. The symptoms were generally those of pulmonary tuberculosis. Sputum was carefully watched for during his stay in the


Hospital (Dr. Osier's clinic), but none was obtained. No microscopical examination could therefore be made.

Autojjsy. The body was that of a slightly built, somewhat emaciated man. The abdomen was moderately distended. The autopsy was made 19 hours after death, the body having iu the meantime been kept on ice. No evidences of post-mortem decomposition were noticeable. The description of the viscera is limited here to the organs especially affected.

The Lungs are voluminous and meet in the middle line anteriorly. They are not bound to the chest wall. Left. The entire lung, except the anterior edge of the upper lobe, which is insufflated, is consolidated more or less perfectly. Where the consolidation is frank the lung presents an opaque appearance, is gray in color, and beginning softening (disintegration with early cavity formation) is going on. The cavities often


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still contain the products of disintegration, and all appearances of reactive encapsulation are wanting. Where the hepatization is less complete the lung tissue is cedematous and swollen, although perhaps not completely airless, and discrete tubercle-like nodules may be seen. The pleura over the hepatized areas is covered with a fibrinous exudate. Right. The consolidation is less extensive and more focal in character, but occupies in places areas as large in extent as 4x5 cm. The pleural cavity contains a small quantity of fluid, pink in color, in which flakes of fibrin occur.

The intestines are moderately distended. The omentum is rolled up ; it occupies a position beneath the transverse colon and extends across the abdominal cavity. The pelvis contains about 15 cc. of fluid of brownish color and mucilaginous consistence. Between the intestinal loops delicate shreds of fibrin exist. In addition smaller and larger nodules resembling tubercles, usually translucent, are scattered irregularly over all the exposed peritoneal surfaces, and occur more uniformly upon and within the thickened, rolled-up omentum. The liver and spleen on section show similar nodules.

The bacteriological examination consisted in the study of cover-slips from the fresh lungs, the inoculation of glycerineagar tubes, and the injection of a suspension from the consolidated lung subcutaneously into a guinea-pig. The histological study embraced all the organs of the body. Cover-slips from the lungs, stained by Gabbett's method, showed no micro-organisms which resembled the bacillus tuberculosis in their morphology. There remained faintly stained in carbolfuchsin upon the cover-slips numerous examples of a branching organism, occurring often in clumps or convoluted masses, among which no ordinary bacillary forms were discovered. From the history of the case, the character of the lesions and the known variation in morphology of the bacillus tuberculosis, it was, for the time, assumed that the organism was a streptothrix form of the former bacillus. Its subsequent study has rendered this assumption highly improbable.

The cultures from the left pleural cavity and the peritoneum remained sterile. Three separate sets of cultures were prepared from the lungs. In all these, at the end of 34 hours, a vigorous growth of a bacillus, identified as belonging to the


group of B. coli communis, had taken place. The streptothrix did not grow. The guinea-pig showed no reaction to speak of at the site of inoculation, the adjacent lymph glands could not at any time be felt; the animal, however, lost in weight and died at the end of the 7th week, at the autopsy showing great emaciation. None of the lymphatic glands were found enlarged ; there were no lesions resembling tubercles in these and other organs, and cultures upon glycerine agar, made from several sources, remained sterile. Cover-slips from the serous cavities, blood and viscera were negative for any kind of bacteria.

The further study of the staining proj^erties of this organism in cover-slips, made from the lungs at the time of the autopsy, shows that as stained by the ordinary methods employed for tubercle bacilli, and decolorized by means of acids, the dye is held very loosely and quite readily given up. The best method of staining is either Gram's or Weigert's modified fibrin stain. The same holds true for its demonstration in the tissues.

The lesions in the tissues are of two kinds, depending in part upon their situation. In the peritoneal cavity tuberclelike nodules are formed, consisting of epithelioid and lymphoid cells with an occasional giant cell. Necrosis by fragmentation is not unusual in the centers of the tubercles, and fibrin, either before or coincident with the necrosis, is commonly observed in the nodules. In the lungs tubercles also exist, but they are less striking than a diffuse exudation of leucocytes, plasma and fibrin which fills the air cells, infiltrates the stroma and tends to undergo necrosis, producing larger and smaller spreading caseous foci of degeneration. The number of masses of the streptothrix is very great indeed and they are in intimate relation to the pathological process.

From these and some other considerations which will appear in the full report, it is believed that the organism is probably a new species, for which the name streptothrix pseudotuberculosa is proposed, and, further, that it is capable of causing in human beings a rapidly spreading and destructive disease resembling phthisis florida, for which the appellation of pseudo- tuberculosis hominis streptotricha seems warranted.


PROCEEDINGS OF SOCIETIES


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of December 7, 1896.

Dr. Thayer in the Chair.

Discussion of Dr. Frledenwald's Paper on Consjenital Motor Defects of tlie Eyeballs. See p. 203, Nov.-Dec. Bulletin, 1896.

Dr. Paton. — This case is of very great interest, and so unique that I feel interested from an anatomical standpoint. Cases of unilateral paralysis are easily explained, but for cases of double paralysis of the 6th nerve there is no anatomical explanation. As yet there has been no demonstration of the crossing of the 6th nerve in man. It has been demonstrated in monkeys. The crossing of the 4th nerve has been demon


strated in man. The further interesting fact that this case brings forward is the relation of the 6th nerve to the oculomotor. There are two possible ways in which these nerves can be related. If you take a section of medulla at the level of the 6th nerve and look at the right side, the fibres are seen to pass across to the left side, and then upward in the posterior longitudinal bundle as far as the nucleus of the third nerve. The main function of that bundle is to connect the nuclei of the cranial nerves, and there you find the connection between the 6th and 3rd. Recently another path has been marked out. The 6th on the right side may pass up on the same side as the rio-ht nucleus, and join the fibres of the 3rd nerve from the other side ; so you have two possible connections. Either the


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6th nerve crosses or the third nerve crosses, and the probability is the latter, because the crossing higher up of the 3rd nerve fibres is the simplest physiological explanation.

Dr. Theobald. — Dr. Friedenwald has had an exceptional experience in meeting with so many of these very interesting cases. It would seem that in this case there is a marked want of power of the internal rectus of the left eye as well as of the extei'nal rectus. This suggests the related cases of congenital ptosis sometimes accompanied by inability to turn the eyes upwards, that one meets with. It is well known that in this case the defect is not central, but is due to absence of or faulty development of the levator muscle of the upper lid and of the rectus superior. Such cases are not so rare as the one shown. I have met with several of quite marked degree. Frequently they are associated with epicanthus. It seems to me that the most probable explanation of this case is that we have here a similar want of development of the external recti. Indeed all the eye muscles here appear to be more or less faulty or weak, for it is difficult to induce the patient to turn his eyes in any direction, all of the movements being defective. We not uufrequently meet with cases of pronounced weakness of the recti muscles, particularly of the external recti, but such cases as the one shown are rare and extremely interesting.

Congenital Facial Diplegia.— Dr. Thomas.

In connection with the case which Dr. Friedenwald has exhibited. Dr. Thayer thought it might be interesting to have this rather unusual case presented to the Society. He has asked me to bring it before you.

The patient, a youth of 19, came to the Hospital from a neighboring State, in the hope that something might be done to improve bis uiifortunate appearance. Dr. Halsted has admitted him to his wards, and it is through his kindness that I have had the opportunity of examining him.

The family history is important. Father and mother are healthy and there is no history of any hereditary taint in either of their families. Patient is the third child of a family of nine. Three children died young, one of these having a niisformed foot. The eldest child, a girl, is perfectly healthy; the second child, a boy, now twenty-one years old, was born in a condition similar to that of our patient. The patient's birth was not particularly difficult and was non-instrumental. It was noticed soon after he was born that he was unable to close his eyes and that his underlip dropped while nursing. In crying his face remained motionless and he was unable to smile. He learned to speak at the usual time but was never able to pronounce certain letters. His general development was good except that he had some glandular trouble. He played with other boys and was able to do everything they did.

You see what a remarkable appearance the patient has ; the face is mask-like and expressionless, the mouth open, the lower lip pendulous, and the lower jaw protruded. He is absolutely nnable to move the muscles of his forehead, and when told to close his eyes he simply rolls the eyeballs up and relaxes the upper lid. He is unable to elevate or pucker his lips, but can move the angles of the moxxth out and down ; in doing this, you see, he brings into play the platysmata. In speaking he cannot pronounce the sounds which require the


use of the lips, viz. b, f, m, p, v. His eyes are prominent; the pupils are equal and react normally to light and during accommodation ; all movements of eyeballs are normal. He complains of being somewhat near-sighted ; there is no disturbance of the visual field. Muscles of mastication unaffected. There is no disturbance of sensation and taste is normal. Tongue is well developed and freely movable, indeed he makes his tongue take the place of his lips as much as possible, drinks and smokes by its aid. I have been unable to discover any abnormality in the muscular development of his trunk or limbs. Stimulating the facial nerves by electricity causes contraction in the muscles back of the ear and of theplatysma. By direct stimulation the platysma can be made to contract.

Before leaving the patient I should like to call your attention to the congenital defect in the right lobe of his ear. You will see that it is notched.

This, then, is a case of congenital facial diplegia. Dr. Friedenwald has told you that certain of the cases of congenital defect of the ocular movements have been associated with a similar condition in the facial muscles, and it is on account of this association that I have brought the case before you at this time.

Dr. Chisolm, of this city, reported one of the very first examples of this condition. In his case there was bilateral paralysis of the sixth and seventh nerves, a combination of the symptoms seen in Dr. Friedenwald's case and of those in the boy whom I have just shown you.

Moebius had a somewhat similar case, which he described in 1888, after which he made a fairly complete collection of all like and analogous cases. These he published in 1892. In this article he expresses the view to which, as Dr. Friedenwald has said, Kiihn takes exception, that the disease depends upon an atrophy of the nuclei, and he proposes the name " Infantiler Kernschwund."

Moebius was unable to find the record of any case in which congenital facial paralysis was unassociated with any defect of the eye muscles. Since then, however, two or three such cases have been described, but these cases were all unilateral, and, as far as I have been able to discover, the case which I have shown you to-night is the first one of its kind to be reported, although I have no doubt that others have been observed.

As to the anatomical condition which underlies these cases not much is known, and it seems scarcely worth while, at this time, to examine the theories which have been advanced.

The aspect and condition of the face in the patient whom we have seen suggest strongly the myopathic face which occurs in certain forms of progressive muscular dystrophy. We have examined the patient thoroughly with this point in view and have been unable to discover any other muscular abnormality, either hypertrophy or atrophy.

It tlierefore seems to me that the case cannot be classed with the progressive muscular dystrophies, although it might be considered as an abortive form of this disease, an explanation which has been given of a somewhat similar condition. As we do not understand the pathology of the muscular dystrophies, such an explanation helps but little. In this connection the condition of the patient's brother is of


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importance, for if, as we are told, his symptoms are quite similar to those of our patient, and no other muscles are involved, it will make the classing of the case with the muscular dystrophies still more far-fetched.*

Dr. OsLER. — I do not think there are any muscular dystrophies of this kind that have that extreme atrophy without any involvement of other muscles. None that I have seen presented that appearance. You will probably find the brother the same as this patient.

Dr. Halsted. — Is the jaw of the brother the same?

Dr. Thomas.— The patient tells me that it is not quite so much so.

Dr. Theobald. — Were there any cases in the family previous to this ?

Dr. Thomas. — Not as far as I can find out, not even an ocular palsy.

Dr. Barker. — The absence of ocular paralysis in Dr. Thomas's case is an interesting feature. In consideration of the anatomical relations of the sixth and seventh nuclei, the occurrence of paralysis of the abducens along with paralysis of the seventh nerve is rather to be expected, if the lesions be in the region of the nucleus and due to pressure or hemorrhage. One of the most curious facts with which the anatomist has to deal is the relation of the fibres of the seventh nerve to the sixth nucleus after they leave the facial nucleus. Why these fibres should run up toward the middle line, turn and run along the fioor of the fourth ventricle and then turn again ventrally and laterally has never been satisfactorily explained. Such an out-of-the-way coui'se seems unnecessary.

During the development of the motor nerves whose nuclei of origin are situated in the medulla and poQS, the motor fibres belonging to the N. accessorius, N. hypoglossus, N. vagus, N. glossopharyngeus, N. abducens, etc., pass directly toward the periphery of the medullary tube and pass through the marginal veil to form the peripheral cranial nerves. The fibres of the N. facialis alone show the well known remarkable discursion. Whatever be the factors which determine the course of these fibres, they are active at a very early period of development, for the relations mentioned are visible in very young embryos. In his lectures on vertebrate embryology last year, Professor His of Leipzig made the ingenious suggestion that the cause of the deviation of the fibi'es of the N. facialis from the course we would expect them to take may possibly depend upon mechanical factors associated with the development of the auditory vesicle, since the ear vesicle is laid down laterally exactly in the region of the sixth and seventh nuclei.

It would be easy to speculate further and to think of such cases as the one before us as instances of congenital nuclear destruction from disturbances of the relations which ordinarily exist between the auditory apparatus and the neural tube, due either to an unfortunate variation or to early intra-uterine pathological lesions. That the affection is bilateral and that more than one member of the same family is diseased would


•The elder brother was seen at his house and was found to be in an almost exactly similar condition to that described above in the case of his brother. Both cases will be reported more fully at a later date.


favor rather than oppose such an hypothesis. It is surprising, considering the extremely complex character of the developmental relations of the internal, middle and external ear, that vicious developments of these parts are not more common than they are. It is interesting to note that, as Dr. Thomas has pointed out in this individual, there is faulty development of a portion of the external ear. Should this man or his brother be the father of children it would be important to determine the presence or absence in them of similar lesions, since, as is well known, variations favorable or unfavorable show a marked tendency to become inherited. That instances of extremely unfavorable variation persisting through many generations are comparatively rare need not surprise us, inasmuch as in the progress of the race, in the course of a very few generations, individuals bearing such peculiarities, owing to their unattractiveness and unfitness, are, as a rule, gently killed out without offspring.

While modern embryology permits the formation of hypotheses such as those here hinted at, it is to be remembered that for any real explanation we must await the results of pathological findings in actual cases. In view, however, of what has recently been done, the problem might perhaps be advantageously approached from the side of teratological experiment.

Meeting ofiDecemher 31, 1896.

Dr. Thayer in the Chair.

A Case of Acquired Paralysis of both External Recti Muscles, with Unilateral Facial Paralysis.— Dr. S. Theobald.

I thought this case would be of interest to show as supplementary to the one exhibited by Dr. Friedenwald several weeks ago. His was a case of congenital paralysis, or perhaps defective development, of the external recti muscles. He pointed out, as one of the interesting features of that form of paralysis, that there was no squint, and explained that in cases of congenital paralysis secondary squint does not usually occur. In the case which I exhibit we have the usual secondary squint found in acquired paralysis of the ocular muscles, and as both external recti are involved, it is of high degree.

This patient is 33 years of age and until August last was employed as a laboring man. His history shows that ten years ago he had a facial paralysis of the left side, and at the same time a paralysis of the right external rectus. There has been little or no change in his condition, so far as we can judge, in all that time. During August last he first developed a paralysis of the left external rectus. As to the cause of these paralyses the history is rather indefinite. It is more than probable, I think, that they are of syphilitic origin. He admits having once had gonorrhcea, and I think there must have been specific trouble also, though the history as to this is not clear. The points of interest are that so many years ago he should have had paralysis of the facial nerve occurring at the same time as the ocular paralysis. If the two had been on the same side it would not be so difficult to explain their co-existence, for we know that the nuclei of the 4th and 6th nerves lie close together in the floor of the fourth ventricle, and it is not uncommon to find both these nerves involved in the same case. It is of great interest, too, that after so long a


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[No. 75.


lapse of time the external rectus of the other eye should have become iuvolved. The paralyses are evidently nuclear, and it would seem that some central change, either inflammatory or degenerative, involved the nucleus of left 7th nerve and the nucleus, which is quite close to it but on the other side of the brain, of the right external rectus, and that after a long lapse of time the left external rectus also became involved.

Paralyses of the ocular muscles are not uncommon. Their origin may be cortical, fascicular, nuclear, basilar, or orbital. Probably the commonest cause of paralysis of the ocular muscles is syphilis. We also often have a paralysis of the ocular muscles in tabes which is quite marked and yet which may in time entirely disappear. Paralysis of the ocular muscles may also be caused by diphtheria, disseminated sclerosis, poisoning by alcohol, nicotine, etc., and a certain class of cases certainly are due to cold. I have seen recently four cases of paresis of the external rectus due to cold or exposure. Such cases frequently occur in rheumatic subjects and are usually due to inflammation in the orbital portion of the nerve, and the prognosis is good.

The most marked symptom in cases of acute paralysis of ths eye muscles is diplopia, which is very annoying. In squint due to hypermetropia there is no complaint of dijjlopia, possibly because it usually develops in childhood ; but in paralytic squint, which oftener occurs in ^ults, diplopia is the most common symptom complained of.

There is one point in regard to this case which I have neglected to mention : this patient has well advanced atrophy of both optic nerves. The discs are decidedly white and the vision greatly impaired, in one eye being only ^^, in the other ^^. The treatment has been the administration of large doses of potassium iodide, and I think there is some slight improvement, but an operation will probably be necessary. It will not be sufficient to perform a tenotomy of the internal recti, but it will be necessary to combine with this an advancement of the externi.

Dr. Thomas. — There is the history of a decided facial paralysis ten years ago, and at present there is contracture of the muscles of the right side of the face. We know that in cases of severe facial paralysis there is very generally developed a secondary contracture of the paralyzed muscles. After a hurried examination it seems to me that upon voluntary effort the patient does move the left side of his face more than the right. An electrical examination would determine the point, but even now I am strongly inclined to the belief that it was the right side that was paralyzed. If this is found to be the case we can easily understand how a single lesion could cause a paralysis of the right 6th and 7th nerves; in fact there are many such cases reported. But on the other hand it is difficult to imagine a lesion involving the right 6th and the left 7th nerves.

Dr. OsLER. — One other point is of interest in this case : whether this may not be a facial paralysis and external rectus paralysis occurring with the secondary symptoms of syphilis, and whether his present paralysis and atrophy may not be the signs of tabes. The fact that he has the knee jerk is somewhat against this, but the persistence of these ocular paralyses is occasionally seen as an initial symptom of tabes.


Dr. Theobald. — I would only say in closing that the knee jerk was examined and found to be up to the usual normal standard. The suggestion of Dr. Osier is well worth considering, whether we are dealing with a greatly different state of affairs now from what originally existed ; whether this present paralysis is a tertiary, while the other was a secondary symptom.

I will be glad to have the patient come to Dr. Thomas's clinic and have the electrical examination made. My diagnosis of left facial paralysis was made simply on the drawing of the face to the right side and the fact that there is a certain blank expression about the left side of the face.

Exhibition of Opiithalmological Cases.— Dr. R. L. Randolph. Bilateral Dacryo-adenitis.

Dr. Randolph reported a case of bilateral dacryo-adenitis (mumps of the lachrymal glands, Hirschberg) in a negro woman thirty-nine years old. He spoke of the case as being one of the few cases reported in this country, the disease being very rare. Both lachrymal glands were so swollen that the upper lids had been pressed down at the outer canthus to such an extent as to hide the outer half of the eyeball. In the case of the left eye the hypertrophied gland had pressed the eyeball inward and slightly downward. The tumors were exceedingly painful to pressure, but at other times she suffered no local pain, the pain then being refeiTed to the sides of the face. There was nothing in her history that would give one a clue as to the origin of her trouble. She was put on small doses of bichloride of mercury and ten grains of iodide of potash three times daily, and frequent hot applications were made to the tumors, and after a month there was a noticeable diminution in their size. Six months after the beginning of the trouble there remained only a slight enlargement of the left


The trouble having passed away it is no longer interesting to show the patient, so she is not here this evening. It is the first case reported in the city, and certainly less than a dozen have been reported in this country.

Dr. Thayer. — In connection with Dr. Randolph's case I should like to say a word with regard to a somewhat similar instance which has been under our observation in the hospital. In 1894 a little girl, 10 years of age, was admitted to the hospital with bilateral hard enlargement of the lachrymal, parotid and salivary glands, for which we were unable to find any cause. The lachrymal glands were to be felt on either side as two small hard shot-like bodies. The child stayed in the wards for many months, and while there developed an ozoena and caries of the nasal bones which was clearly syphilitic in nature. Under treatment with mercury and iodide of potassium the glandular swellings slowly but completely disappeared. While in the hospital, however, some of the cervical and lymphatic glands became enlarged and remained so after treatment with mercury and iodide of potassium, and the child has since showed evidences of a tuberculous peritonitis. The enlargement of the lachrymal glands was very striking, though never as marked as in Dr. Randolph's case; it has entirely disappeared.


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Operations for Cataract.

The other cases which I have to exhibit are some of the cataract cases upon which I have operated in this Hospital during the last summer. There are 12 or 13 here to-night. Some of them have interesting histories. One, an old man, 88 years of age, was operated upon early in September, and on the night of the operation had an attack of acute mania. He tore the bandage off several times, and finally had to be tied in bed, but in spite of that has a good result. When we consider how slight a disturbance may sometimes cause the operation to go to the bad this is rather a remarkable recovery. The bandage was disarranged at least three times. After the atropia was withdrawn he regained his senses and was rational for three days. One night after that he had another attack, jumped from his window, scaled the fence and was making his way homeward when found. Strange to say it had no effect upon the ultimate result.

The next case is a rare one. I operated for cataract early in June and the anterior chamber remained open after the operation for 17 days. At the last meeting of the American Ophthalmological Society I asked several of the members what was the longest time they had ever seen the anterior chamber remain open, and the longest period given in reply was 11 days. Four weeks after the operation when this patient left the hospital he had i^ vision, which is very good practical vision.

Very frequently in cataracts there seems to be a stage where they make no progress toward maturity. That was the case with this woman, aged 63, who, while having sight enough to get about, was unable to do work. Here I performed the maturing operation. This consists in doing an iridectomy and practicing massage upon the lens through the cornea. The cataract was ripened, then exti'acted. With the exception of that case I have performed the simple extraction, and in several of them there is no objective evidence of an operation having been performed.

Demonstration of Florence's Iodine Test for Seminal Stains.

— Dr. Lewellys F. Barker.

Professor Florence of Lyon has recently published in the Archiv d'Anthropologie a very delicate test for human seminal stains. He uses a mixture of iodine, iodide of potash and water not unlike the ordinary Lugol's solution.

To apply the test, if the seminal stain be upon linen, a small piece of the stained fabric is moistened with water, placed upon a glass slide and a drop of the reagent added beneath the cover-glass. If the stain be due to semen a very distinct precipitate of crystals results. The form of crystals is not unlike that of ordinary haemin.

We have used the test in the course in normal histology and find it very easy to apply and extremely delicate. The reaction is not yielded by blood, saliva, nasal mucus, vaginal mucus, urethral mucus, nor by the semen of other animals. I have placed under the microscope one specimen in which the seminal reaction is apparent, and under the other microscopes a number of other fluids mentioned in which no reaction has taken place. Urine sometimes throws down yellow-brown globules, but as far as we have been able to make tests, defi


nite crystals, likely to be confused with those of the reaction, are never deposited. Whether or not urine containing semen would yield the reaction I have not yet had the opportunity of testing; but inasmuch as minute quantities of the seminal fluid on linen will afford the reaction, it is very probable that urine containing this substance would also yield it. Some alkaloids are capable of yielding similar precipitates, a fact which must be borne in mind in medico-legal cases. Just what portion of the semen is concerned in the reaction has not yet been made out; it would be easy to ascertain this by testing the individual constituents of the seminal fluid obtained, say from the vas deferens, vesiculiE seminales, prostate and Cowper's glands at autopsy. Urethral mucus, as will be seen under one of the microscopes, does not yield the reaction. In case no single one of these constituents afforded the reaction, the latter must be due to some substance produced on their admixture.


NOTES ON NEW BOOKS.


The Practice of Medicine. A Text-book for Practitioners and Students, with special reference to Diagnosis and Treatment. By Jambs Tyson, M. D., Professor of Clinical Medicine in the Unisity of Pennsylvania, etc. Illustrated. {Philadelphia: P. Blakision, Sondb Co., 1896.)

This is in every respect an admirable boolt. The author's statement that it tias taken several years of labor is borne out by the careful and thorouglily conscientious way in which the suliject has been treated. It is a work of nearly 1200 pages, larger than the recent text-books issued in this country, containing on the whole rather more mattereven than Flint's, which is a very closely printed book.

Ttie author's method of dealing with a subject is well illustrated in the consideration of the important subject of myxoedema. Following the definition — and by the way the text-book is quite strong in clear, practical paragraphs defining diseases— the history of our knowledge of the affection is considered in nearly threefourths of a page. Dr. Tyson has in nearly every section dealt in a most instructive way with the historical development of the knowledge of the different diseases, and in myxoedema it is of course particularly interesting. I do not think that the statement is altogether clear about the dispute between Reverdin and Kocher as to the discovery of operative myxcedema. Unquestionably Reverdin published the first note in October, 1882, but he did not at that time appreciate fully the remarkable character of the changes following thyroidectomy. Kocher distinctly states that in the autumn of 1882, in Geneva, he spoke to Professor Reverdin of the remarkable sequences of the operation, and that Reverdin six days later read a paper on the subject. In Kocher's paper, which appeared in the spring of 1883, the description of operative myxoedema as we know it now, and which he called cachexia strumipriva, was fully and clearly drawn, and he certainly appreciated at that time, as Reverdin did not, the serious effects which might follow total extirpation. In the succeeding paper by the brothers Reverdin they recognized the condition as identical with myxoedema and called it myxoedeme operatoire. Three forms of myxoedema are recognized : pure myxoedema, myxcedema associated with congenital or sporadic cretinism, and operative myxcedema. There is in addition a full description of cretinism. On the subject of exophthalmic goitre, though the disease is placed under diseases of the thyroid gland, Dr. Tyson states that the neurotic nature of the disease is now generally admitted. He holds that the sympathetic neurosis theory


explains the symptoms rather more satisfactorily than any other. His practice is better than his precept in this respect, since he places the disease where it probably belongs, among those of the tliyroid gland. We are glad to notice that he insists upon the priority of the description by Graves. Of this, of course, there can be no doubt, though Parry and others published individual cases. Graves' clinical lecture in 1835 gave the first good description of the affection.

Naturally in a new textbook one turns to certain of the diseases about which there is still a good deal of difference of opinion. Appendicitis receives a very thorough and satisfactory treatment. There is no work in English which gives so good an account of the history of the affection. We are glad to see that Dr. Tyson does not consider it necessary to speak of a typhlitis, stercoral or otherwise. It is satisfactory to see that the name even does not occur in the index. lie describes catarrhal, ulcerative and interstitial forms of appendicitis. The clinical description of the different varieties is admirable. On the all-important matter of treatment the author takes rather advanced ground, stating that "the diagnosis being established, operative treatment should be recommended, except in those cases where the disease is so far advanced as to make it unlikely that the patient will be saved by operation." He thinks that the operation after the first attack is safer than during the first attack. On the much debated point of purgatives he leaves the matter to the circumstances of the case and the good judgment of the attendant, as the results may be either very happy or very mischievous. He believes that if there is doubt it is best not to purge.

The article on typhoid fever, with which the book opens, is in every way worthy of the great importance of the subject. The author is a strong believer in the use of the cold bath, and on the question of treatment he everywhere displays sound judgment.

We have said enough to indicate the importance of the work, its thoroughness, and its reliability in all practical details. The publishers are to be congratulated on the appearance of the volume. It is one of the handsomest works issued of late years in this country, and the type and paper are very much above the average. Altogether Tyson's Practice forms a very welcome addition to our textbooks, and we predict for it a most successful career.

An American Text-book of Applied Therapeutics, for the use of Practitioners and Students. Edited by J. C. Wilson, M. D., assisted by Augustcs A. Eshnek, M. D. Pp. 1-1326. {Philadelphia: W. B. Saunders, 1896.)

Since the main object of medical studies must always be the formulation of methods for the prevention and cure or alleviation of disease, it necessarily results that laboratory researches and clinical observations must ultimately be valued in proportion as they have brought us nearer to the attainment of these aims — in other words, according to the advances which have been derived from them in the establishment of a rational system of therapeutics. The world at large is apt to look at results rather than methods, and the busy practitioner may justly demand that the previous studies and experience of others should be presented to him in aconcrete form. For these reasons the status of medicine at any particular period will, to a great extent, be gauged by the therapeutic measures which prevail at that time, and of which the textbooks dealing with the subject are the exponents.

Graduates of twenty years ago will probably remember a time in the first few years of their practice during which they were tempted to become adherents of the doctrines of therapeutic nihilism. They had gone forth armed, they had been taught and for a time had firmly believed, with agents with which they could infallibly combat each and every untoward symptom. Is it to be wondered at that many of them in a short time exchanged their early therapeutic optimism for a hopeless therapeutic pessimism? Could they not justly reproach for this the faulty teaching which had been accorded to them?


Medicine is still to a great extent an empirical art, but although we can hardly hope that it will ever be numbered among the exact sciences, there are signs which indicate that by slow degrees we are attaining to a therapeusis which may always be at least rational.

The book before us shows a decided advance, not only because it registers real progress made in our knowledge of disease processes and in our methods of treatment, but because it shows that the difficult subject of therapeutics is now being attacked in a frank and true scientific spirit. The writers have been chosen from among men who have brought to bear upon the subjects allotted to them not not only the results of a profound study of the existing literature, but also those which can be obtained only by a wide personal experience. They are not mere compilers; they know whereof they speak. If not all of them have added much that is new, they have at least accepted the dicta of others only after a painstaking proving of their statements. They have chosen the middle ground, and while confident that much can be accomplished by the use of the various therapeutic measures which they recommend, they do not by the employment of specious generalities attempt to conceal those points upon which our present knowledge is still defective. They hold a strong position midway between therapeutic optimism and therapeutic nihilism. Above all and first of all they preach the doctrine of prophylaxis.

In many of the articles a short account of the more prominent manifestations of the disease underdiscussion will be found, which, although adding considerably to the bulk of the book, will assist the reader materially in better appreciating the treatment recommended later. It is impossible to speak here in detail of all or of any of the various contributions. In his article on tuberculosis, Whittaker summarizes our present knowledge upon prophylaxis in general, hygiene and climatology, and has ably marshaled all the recent experience, upon which he formulates a treatment which, if it contains little that is really new, is perhaps the best at hand. If his conclusions as to the advantages to be obtained by the use of tuberculin are not in accordance with those of other authors, his results certainly deserve the most respectful consideration. Tyson's article upon the diseases of the kidney is brief but admirably comprehensive. In speaking of typhoid fever, Wilson, after a careful consideration of other methods, not only endorses the cold bath treatment but repudiates the notion that it is cruel. This latter view will certainly not be conceded by many even of the most enthusiastic supporters of the procedure. Serum therapy receives a full share of attention, and the subject has been treated, by the writers upon the conditions for which it has been advised, with a full appreciation of its importance. Whatever may be the opinion with respect to Laveran's vie w as to the identity of the parasite for the different forms of malarial fever, the careful and precise treatment which he lays down will not easily be improved upon.

Another point to be noted is the comparative simplicity of the prescriptions which are given ; we are grateful for further evidence of the decline of polypharmacy. It would seem that we are beginning to appreciate Huxham's advice, " The physician should select a few (drugs) of the most effectual forhis useof each sortand stick to them and not run into an immense farrago which some are so fond of." Many of the illustrations are good, but not a few are superfluous. As might be expected, the book lays no claim to perfection. The student who looks to it for infallible remedies for every disease will naturally be disappointed ; the man of more moderate demands will find in it much that will help him in his daily work, and much that will stimulate him to the observation of disease processes and of the way in which they may best be met.

Frank R. Smith.

Die Fiirbetechnik desNervensystems. By Dr. B. Poll.^ck. {Pub lishcd by 8. Karger, Berlin, 1897.) Pp. 1-130.

This little book will be welcomed by neuro-histologists everywhere. It gives briefly the important steps in all the more impor


June, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


135


tant methods used in microscopic examination of the nervous system, including those of recent date. In the first section the technique of cutting up the brain at autopsy is described, togetlier with the methods for preserving the brain whole and forreproduc. ing plastically the specimens found at autopsy. In section two the general technique of hardening, staining, emliedding and section. ing is discussed. The methods of making serial sections, including the recent method of Flatau for making serial longitudinal sections of the whole spinal cord, are considered. We are glad to find mention made in section three of the work of Donaldson and others concerning the alteration in weight of the brain and cord after pri-servation in different hardening fluids. Too little attention has been paid to such alterations in previous books on technique. Apparatus for drawing and photography are described in section four. In the next section the methods of staining and impregnation are taken up. The various ways of demonstrating nerve cells and their axones and myelin sheaths are outlined. Golgi's method, Ehrlich's metliod and the new stains for neuroglia have been carefully considered. Nissl's method is given, and also Held's modification of it. The differentiation with alum solution is simple, easy to manage, very inexpensive, and yields in the reviewer's experience results fully as satisfactory as those afforded by the method with anilin oil and alcohol. In the sixth section certain general points to be borne in mind in the examination of normal and pathological cases are emphasized. It is particularly gratifying to find epitomized at the end of this section the routine methods employed in Waldeyer's laboratory for the study of the central and peripheral nervous systems. A brief bibliography is appended as well as an index. The book costs only two marks, and will probably find its way into many laboratories, where it will prove a safe and convenient guide. L. F. B.

Arbeiten aus dem Institut fiir Anatomie und Physiologic des Centralnervensystems an der Wiener Universitiit. Herausgegeben von Professor Dr. Heinrich Obeesteiner. Y. Heft, mit 5 Tafeln und 46 Abbildungen im Texte. (Leipzig und Wien : Franz Deuticke, 1897.)

The most recent number of the fasciculi which are appearing at intervals from Obersteiner's laboratory is fully up to the general standard set by the preceding numbers. Itcontains seven articles, one of which, on the innervation of the blood-vessels of the brain, is by Obersteiner himself. In this article Obersteiner discusses the work of previous investigators and describes and pictures a small artery of the pia mater stained with gold, in which he brings the direct anatomical proof that the finer intra-cranial vessels, at least within the pia mater, possess their own nerves. He refers briefly to the physiological and pathological significance of such innervation.

Schlagenhaufer contributes an article on the course of the fibres in the optic paths, in which is discussed also the tabetic atrophy of the optic nerve. He believes that there exists sometimes, at any rate, a compact uncrossed optic bundle which, however, forms only a part of the uncrossed bundle, and probably corresponds to the inferior (external) fibres. The direction of the course of this bundle gives, he thinks, in all probability, the anatomical course of the uncrossed bundle. The question of the total or partial crossing of the optic nerves in man must, therefore, be regarded as decided in favor of the latter through anatomical investigation. He thinks that by means of a scheme constructed accordingly it is possible to explain all the hemianopsias. As regards Gudden's commissure, he makes out that a part of the fibres stream into the ansa lenticularis to become connected with both lenticular nuclei. Some of the fibres run in the peduncle of the hypophysis. In front of Meynert's commissure in the upper anterior part of the chiasm there is a small system of fibres which remains intact when the optic nerves and chiasm atrophy. He thinks it possible that the tabetic atrophy of the optic nerves may be due to pressure at the foramen opticum.


F. Rezek describes and pictures a primary polymorphous sarcoma of the brain.

Pfiegler and Pilcz contribute along article entitled "Beitriige zur Lehre von der Mikrocephalie." They describe twelve cases of their own, with consideration of no less than 365 bibliographic references.

An interesting study of the histology of the ganglion cells of the horse in normal conditions and after arsenic poisoning is given by H. Dexler. Two beautiful plates accompany his article. The same writer publishes also a short note on the course of the fibres in the optic chiasm of the horse.

Julius Zappert, in an article on degenerations in the spinal cord and medulla oblongata in the child, embodies the results of his studies on the spinal cord and medulla of children who have died during the first three years of life. He has used Marchi's method and describes his findings with especial reference to the changes in the various nerve roots. L. F. B.


BOOKS RECEIVED.


Tuberculosis. By William Osier, M. D. 8vo. 1897. Reprinted from " Loomis' System of the Practice of Medicine," New York and Philadelphia, I, pp. 731-848.

Diseases of the Ear, Nose and Throat and their Accessory Camties. A condensed text-book. By Seth Scott Bishop, M. D., LL. D. 1897. 8vo, -196 pp. The F. A. Davis Co., Philadelphia, New York, Chicago.

Annual Report of the Trustees of the State Hospital for the Insane, at Warren, Pennsylvania, for the year ending No-oember 30, 1896, to the Board of Commissioners of Public Charities. 1897. 120 pp. Herald Printing and Publishing Co., Erie, Pa.

Medical and Surgical Report of the Presbyterian Hospital in the City of New York. Edited by A. J. McCosh, M. D., and W. B. James, M. D. Vol. II, Jan., 1897. 8vo, 272 pp. Trow Directory Printing and Bookbinding Co., New York.

Ouy's Hospital Reports. Edited by E. C. Perry, M. A., M. D., and W. H. A. Jacobson, M. A., M. Ch. Vol. LI, being Vol. XXXVI of the third series. 1895. 8vo, 272 pp. J. & A. Churchill, London.

Guy's Hospital Reports. Edited by E. C. Perry, M. A., M.D. , and W. H. A. Jacobson, M. A., M.Ch. Vol. LII, being Vol. XXXVII of the .third series. 8vo. 1896. 230 pp. J. & A. Churchill, London.

Lectures on Pharmacology for Practitioners and Students. By Dr. C. Binz. Translated from the second German edition by Peter AV. Latham, M. A., M.D. Vol. II, 1897. 451 pp. 8vo. New Sydenham Society, London.

A Pictorial Atlas of Skin Diseases and Syphilitic Affections, in Photolithochromes from Models in the Museum of the St. Louis Hospital, Paris. With explanatory woodcuts and text. By E. Besnier, A. Founier, et al. Edited and annotated by J. J. Pringle, M.B., F. R. C. P. Fol. 1897. Part IX. W. B. Saunders, Philadelphia.

Transactions of the Indiana State Medical Society, 1895. Forty-sixth annual session held in Indianapolis, Ind., June 6th and 7th, 1895. Svo, 534 pp. Carlon & Hollenbeck, Indianapolis.

Hysteria and Certain Allied Conditions. By George J. Preston, M. D. 1897. Svo, 298 pp. P. Blakiston, Son & Co., Philadelphia.

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL

Bv JOHN s. Billings, m. D., ll. D.

Contaiulng 56 large quarto plates, phototypes, and litliographa, with views, plans and detail drawings of all the buildings , and their Interior arrangements— also wood-cuts of apparatus and fixtures; also 116 pages of letter-press describing the plans followed In the construction, and giving full details of heating-apparatus, ventilation, sewerage and plumbing. Price, bound in cloth, $7.60.


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rXo. 75.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Report In Pathology.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By P. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berklet, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermatology. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmet Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of Molluscum

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report In Pathology. An Experimental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By JoHX N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleor, M. D. Cases of Post-febrile Insanity. By William Obler, M. D. Acute Tuberculosis in an Infant of Four Months. By Hahrt Toclmin, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine. Tubercular Peritonitis. By William Osler, JI. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecology. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March S, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D, The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By HnuTER Robb,

M. D. The GonococcuB in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Pentoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one GjTiecological Cases. By Howabd

A. Kelly, M. D., and Albert A. Ghriskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of (3hecking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Oitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Surgery, I. The Treatment of Wounds with Especial Reference to the Value of the Blood Clot

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, 1. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By Adqdst Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Pathology, I. Amffibic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleub, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in Pathology.

Papillomatous Tumors of the Ovary. By J. Whitridqe Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridqe Williams, M. D. Report in Pathology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report In Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring the Co'njugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retrofle.xed Uterus. By Howard A Kelly, M. D.

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 A. L. Stavelt, M. D.


Gynecological Operations not involving Cceliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Hsmatokolpos and Bxmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Neurology. Dementia Paralj-tica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of .Whs- musculu^; The Intrinsic Nerves of the ThjToid <31and of the Dog; The Nerve Elements of the Pituitarj' Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from Jime, 1889, to January, 1894. By W. S. Halsted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Pathology. Deciduoma Malignura. By J. Whitridqe Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D.. and J. Hewetson, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Feyer. By William Osler, M. D., n-ith additional papers by G. Bluher, M. D., Simok Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. About 500 pages, many illustrations.

Report in Neurology.

Studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory. — Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. E.xperimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol) ; Part II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part HI. — Ricin Poisoning. — Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia. — Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V. — Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Pathology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S. Cullen, M. B.

Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. WiLKlNS, M. D.

Adeno-Myoma Uteri Diffusum Benignmn. By Thomas S. CJullen, M. B.

A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. Bj William D. Booker, M. D.

The Pathology of Toxalbumin Intoxications. By Simon Flbxnieb, M. D.

TJie price of n set hound in cloth [Vols. I-1'I'\ of the Hospital JSepoi-ts is $30.00. Vols. I, II and III are not sold separately. The price of Vols. IV, V and VI is $5.00 each.


MONOGRAPHS ON DERMATOLOGY, MALARIAL FEVERS AND TYPHOID FEVER. The following papers are reprinted from Vols. I, IV and V of the Reports, for thoee who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. GiLCHRiST, M. D., and Emmet Koeord,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

J3.00. THE MALARIAL FEVERS OF B.-ILTIMORE. By W. S. ThaTER, M. D., and J.

Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARH.

By Lewellys F. Barker, M. B. 1 volume of 280 pages. Price, in paper, $2.75. STUDIES IN TYPHOID FEVER. By William Osler, M. D., and others. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, bound in paper, $3.00. Subscriptions for the above publications may be sent to

The Johns Hopkins Press, Baltimore, Md.


The Johns Hopkins Hospital Bulletins are issued monthly. They are printed hy THE FRJEDENWALD CO., Baltimore. Single copies may he procured from Messrs. CVSHINO & CO. and the BALTIMORE NEWS COMPACT, Baltimore. Subscriptions, $1.00 o year, may he addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; single copies will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. VIII -No. 76.]


BALTIMORE. JULY, 1897.


IPrice, (5 Cents.


coisrT:E]isrTS.


PAGE

Studies on the Lesions induced by the Action of certain Poisons on the Cortical Nerve Cell. Study VII : Poisoning with Preparations of the Thyroid Gland. By Henry J Berkley, M.D., Five Successful Cases of General Suppurative Peritonitis treat ed hy a New Method. By J. M. T. Finney, M. D.,

An Experimental Study of the Treatment of Perforative Peri'


137


141


PAGE.

By Arthur


tonitis in Dogs by a New Method of Operation

W. Elting and Wm. J. Calvert, ......

Squamous Epithelioma and Epithelial Hyperplasia in Sinuses and Bone following Osteomyelitis. By S. M. Cone, M. D., ■

On the Blood-Pressure-Raising Constituent of the Sui)rarenal Capsule. By John J. Abel, M. D., and Albert C. Crawford, M. D.,

Notes on New Books,


151

158


STUDIES ON THE LESIONS INDUCED BY THE ACTION OF CERTAIN POISONS ON THE

CORTICAL NERVE CELL

STUDY vn.

POISONING WITH PREPARATIONS OF THE THYROID GLAND. By Henry J. Berkley, M. D., Associite in Neuro-Patholoyii, The Johns Hopkins Universily.


The favorable side of the administration of the thyroid extracts is shown in the very numerous articles in current medical literature published both in this country and in Europe. Comparatively few of these papers treat of other than the bare clinical results from the most auspicious standpoint, and it is quite safe to say, after a review of some of them, that the results would have been as brilliant had no medicament been administered.

It is nevertheless true that the extract, when administered to either man or the lower animals, will occasion very grave symptoms of a toxasmic nature, symptoms that involve the cerebral, the vaso-motor and digestive functions, and perhaps also the normal action of those ductless glands that throw into the circulation a potent though unknown substance ; and when this administration is pushed even to a moderate degree death is almost invariably the result, either through the advent of convulsions, or extensive loss of weight with indications of profound poisoning of the central nervous system, shown by the change in the heart's action and in the respiratory movements.

A medicament having these qualities cannot, therefore, be administered with impunity to every sane or insane patient,


and it was therefore directly for the purpose of ascertaining the toxicity of one of the best known varieties of the thyroid extract that the following series of experiments was undertaken.

The first portion of the investigation was made upon eight patients at the City Asylum, who, with one exception (No. 1), had either passed or were about to pass the limit of time in which recovery could be confidently expected. To these patients the thyroid tablets, each pill representing five grains of the fresh sheep's gland, were administered, the dosage beginning always with a single pill daily for a period of three days, then, after a certain tolerance had been established the dosage was increased to two tablets daily, and, unless the symptoms induced became grave, the number of pills was increased to three daily, the length of continuance depending upon the results.

Loss of weight always attended the administration of the tablets, as did disturbances of the circulation in the form of tachycardia and enfeeblement of the cardiac action. Digestive disturbances and slight pyrexia were present in more than half the cases. A peculiar odorous sweating was noticed with two patients, and increase of the cutaneous transpiration in


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[No. 76.


all. Irritability and a greater or less degree of mental and motor excitement were remarked in all cases, no matter how depressed or demented they had been previous to the administrations. Two jjatients became frenzied, and of these one died before the excitement had subsided, the immediate cause of the exitus being an acute disseminated tuberculosis. A peculiar gelatinous feel to the integument of the forehead and cheeks, precisely similar to that in myxcedema, combined with puflBness of the skin about the malar prominences, was very noticeable in those cases in which the administration of the extract was continued for any length of time. Urinary examinations were made several times before the commencement of the administration of the thyroid, and several times during its administration, but only for the purpose of noting the presence or absence of albumen and sugar. In the abstracts this analysis is mentioned only when there is evidence of the presence of these abnormal constituents.

Abstracts of Histories of Insane Patients Treated WITH Thyroid Extract.

I. Adolescent insanity. Martha H., set. 17. Sister insane. Admitted with melancholic symptoms accompanied by considerable mental confusion. Occasionally had to be fed with stomach tube. Could not speak, and it was imjoossible to determine what delusions were present. After being several weeks in the Asylum she partly recovered, and then relapsed, and there appeared to be considerable mental reduction after the lapse of several months. Then began to brighten, and take more interest in her surroundings, also to gain flesh. The thyroid gland was, apparently, small on palpation. Weight at beginning of the thyroid administration 115 pounds. A single thyroid tablet was administered for ten consecutive days, at the end of which time there was slight febrile reaction, with a pulse ranging from 100 to 110 (normal 78). The mental change was very slight, patient exhibiting some irritability, but nothing more. The weight is now 109 pounds.

On the fourteenth day, the thyroid being continued, the first signs of improvement were noticed. Patient became brighter, ate food without compulsion, and on the twentieth day volunteered to do work about the ward and conversed rationally. The thyroid extract was discontinued on the twenty-second day, and patient was discharged one week later, six months after her admission, and did not relapse.

II. Melancholia folloioed hij deep dementia. Olivia P., ist. 37. Education fair. No heredity. Married. Nutrition poor. Thyroid fairly well developed. Weight 100 pounds. Oil admission refused to speak, and would not take food.

Patient was deeply demented, and quiet for several months before the thyroid treatment was begun. She lost flesh very rapidly, and on the eleventh day of the treatment showed pronounced mental and motor excitement. Slight febrile reaction, accompanied by a pulse rate of 120 beats. On the twelfth day she passed into a state of frenzy, the motor excitement being more pronounced than the mental symptoms. The thyroid extract was now discontinued, but the excitement kept up, despite numerous attempts, with narcotics, baths, and systematic exercise, to allay it, for seven weeks, at the end of which time she died with the clinical


evidences of acute miliary tuberculosis. An autopsy was not permitted.

III. Beginning dementia. Frank G., aet. 20, well educated, was admitted to the asylum suffering from an attack of acute mania. There he improved, but was taken out too soon, relapsed, was readmitted, and then gradually demented. Thyroid of normal size. Is good tempered. Weight at beginning of thyroid administration 125 pounds. On the seventh day of the treatment became quite irritable and impatient. By the fifteenth day he was so quarrelsome that it was necessary to restrain him. During these 15 days he lost five pounds, and there was considerable tachycardia and sweating. The myxoedematous symptoms were not so pronounced as in some of the other cases. The administration of the extract now being discontinued, he regained weight, became more quiet, and after the lapse of several weeks he was sent to his friends somewhat improved.

IV. Dementia. John B., fet. 31, admitted as a case of acute mania, and after a period of four months gradually demented, became quiet, and not at all irritable. Thyroid gland normal. Treatment was now begun, and within a week there was j^ronounced febrile reaction, with tachycardia and sweating. There is a marked difference in the asjject of the face, which now appears puffed and rounded, in contrast to the former rather emaciated appearance. The facial expression also became anxious, but there was no pronounced excitement. The treatment was continued thr»c weeks longer, without producing other change than an increase of the myxcedematons characteristics, and was then discontinued. From a mental standjwint, the course of the patient's disease was now rapidly downward, and he became absolutely demented and degraded.

V. Chronic vielancholia. Marcus Z., set. 30, Russian Jew, admitted to the asylum with alternating melancholia and mania. Thyroid normal. Much emaciated from chronic diarrhcea. Refused food at first. Has been quiet for some months, suffering from well marked delusions of persecution. Under enforced feeding became well nourished, but not less melancholic. Six months after admission treatment with thyroid extract begun. One tablet for ten days, two for four days, and three daily for two weeks longer. On the 11th day became much excited, complaining that his countrymen wished to kill him. There was slight febrile reaction and increase in the pulse rate to 120 (normal 75). The cheeks soon began to assume a marked puflBness, and on palpation had a jelly-like feel. No other phenomena were noticed, except that at the end of the month's treatment he had lost eight pounds, which he rapidly regained after it was discontinued. Then he also became quiet, and at the date of writing still remains an inmate of the institution, retaining his oldtime delusions.

VI. Dementia following puerperal melancholia. Katie S., ret, 35, was admitted in 1893, four weeks after confinement. Recovered in about six weeks, was taken home, and there relapsed and became permanently demented. Is untidy, mischievous, but never excited. Pulse rate normally 85 to 90. Thyroid normal. Was placed on thyroid extract, one pill, then two pills ilaily. lu second week marked febrile reaction.


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pulse 120 to 1.30, very weak. There is considerable sweating. Facial puffiaess well marked. Has become very irritable, restless, aud difficalt to control. Thyroid extract discontinued after three weeks' administration, after which she gradually returned to her usual condition.

Vn. Deep dementia foIJoioing confimonal mclnnrlioliu. ilaggie E., set. 2.5, was admitted in December, 1893. Thyroid normal. When treatment with the thyroid extract was commenced was untidy and deeply demented. On the tenth day there was slight febrile reaction accompanied by slight motor excitement. These symptoms abated in the course of a few days, though the administration of the thyroid extract was continued, and, after three weeks, no improvement having been noticed, it was discontinued.

VIII. Imbecility with recurrent mania, followed by apparent dementia. C. B., aet. 21, admitted with second attack of excitement in December, 1895, and within a few weeks became apparently deeply demented. Thyroid gland very small. Administration of the extract was begun, and after a few days there was febrile reaction, considerable sweating, and a myxcedeniatous appearance of the integument of the face. The pulse rate altered from 72 to 110, and the patient lost weight rapidly. There were also considerable motor and mental excitement, with the febrile symptoms, all of which gi'adualiy abated, though the treatment was faithfully kept up for a considerably longer time. The patient has had several lucid intervals during the fall of 1896, but now seems completely demented.

The above experiment upon eight human subjects points out conclusively that the administration of even the very best and purest of the commercial desiccated thyroid tablets is not unattended by danger to the health and life of the patient, and that at times the administration of very limited amounts of the gland may be followed by symptoms not only difficult to control, but of very marked influence upon the future mental powers of the subject.*

These results obtained, we then decided to further pursue our experiments upon the lower animals, to determine the amount necessary per kilo of weight to cause death, the immediate cause of the dissolution, and the lesions, both macroscopic and microscopic, present at death, especially those pertaining to the cerebrum.

Through the kindness of Dr. Crawford of the Pharmacological Laboratory, who undertook the ordering of the administration to the animals, we obtained material from five mice and three guinea-pigs, to which the same desiccated sheep's thyroid tablets used in the first part of the investigation had been fed; also the cerebrum from one guinea-pig to which had been administered thyroid extract, and the cerebrum of a dog from which the thyroid had been extirpated about one year previous to its death, but in which, at the autopsy, supernumerary thyroids were discovered, though the animal during life had exhibited minor symptoms of a cachexia.

A portion of the material for microscopic examination was

  • I do not take into consideration the possible presence of putrefactive products in the tablets, as they were perfectly free from all

evidences of decomposition.


hardened in Muller's fluid for after-treatment according to the silver-phospho-molybdate formula, and another portion in alcohol, for staining with the anilines, hematoxylin, aud more particularly to examine into the lesions of the blood-vessels, both in the abdominal viscera and cerebrum.

The five mice were first fed with the tablets. All of them ate the pills readily to obtain the sugar coating them. For a few days there was no appreciable effect. Then they grew dull, the cheeks became puffy, there was trembling and increase of the frequency of the respiratory movements, and death rather suddenly.

Abstract of the Histories of the Thyroid Mice.

No. I. Administration of the tablets commenced Aug. 22, '96. One pill 32nd; three, 24th. Animal remains bright and eats other food ; 2.5th, two tablets. On 26th, it seems frightened and the face appears swollen ; on the 37th instant, it is still trembling very greatly, and no pill was given. On the 28th, it is very much brighter and the trembling has almost ceased. On the 29th, is bright, and feeding of the thyroid was again begun. Sept. 1st, three pills were fed, the animal eating nearly the whole quantity. The 2nd instant, the face is again swollen, and on the 3rd, refused to eat a portion of the tablets, and has become quite dull. On the 4th and .5th instant, the animal continued dull, trembling, aud looks weak and sick. On the 7th, the eyes are very bright, and there is slight emaciation. Five pills were given, but not all were eaten. On the 8th, only two pills were taken ; there is much trembling. Died during the night of the 9th instant, having eaten a portion of the tablets left in the cage.

The autopsy showed congestion of all the viscera, but without hemorrhage. The brain was soft.

No. II. On the 33nd August, cue pill administered, on the 23rd aud 24th, the same quantity, but little not being eaten. On the 35th, two pills were eaten, the animal still remaining bright. On the 36th, two tablets were eaten, and the face shows signs of swelling. On the 27th, the testes have become swollen, in addition to the face, but the appetite is still retained. On the 38th, the eyes are partly closed, and on the 29th, the animal is trembling, the legs are dragged, but it still takes care of its coat.

September 1st, the animal is dull, the face much swollen. Three pills were eaten. On the 3rd, is much brighter, sleeps well, but has not taken all the pills during the last two days. On the 5th instant, will hardly touch the sugar-coated tablet. On the 7th, the face is markedly swollen, the animal is dull, the hair less sleek, and the eyes almost closed. Kespi ration 134 per minute. Died in convulsions at 2.30 1*. M.

The autopsy was performed immediately. Besides some unimportant congestion of the abdominal viscera there were no ascertainable lesions.

No. III. Commenced feeding on 33ud August, but no symptoms were noticed uutil the 36th, when the face became slightly swollen and the animal declined to eat the pill. On the 28th, there is slight trembling. On the 30th, the trembling continues. On Sept. 3nd and 3rd, took daily three pills. On the 5th, is dull, tottering, very weak. On the 7th instant, the hair is rough, and it seems weak, hut eats the pills


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well. On the 8th, is trembling very much, but eats the pills. Died during night.

Autopsy showed congestion of the abdominal viscera. Brain rather soft.

No. IV. Feeding commenced on August 'Z2nd, but does not eat the tablet well, hardly averaging J of a pill daily. On the 26th, the animal is bright, but the face is slightly swollen. On the 29th, refused to eat pill, but remaiued dull until September 3nd, and thereafter refused to eat pill at all. On the 12th instant, had apparently fully recovered.

No. V. Administration commenced on the 22nd August, and the dried gland was all eaten. On the 26th instant, the face is swollen. On the 28th, there is much trembling, but three pills were eaten. On the 29th, would not eat pill, but on Sept. 1st ate four pills. On the 5th instant, is trembling considerably, but ate two pills. On 8th instant, was bright, though trembling. On morning of 9th instant, found dead in cage. The autopsy showed the usual congestion.

Abstract op the Histories of the Thyroid Ctuinea-Pigs.

No. I. Fed with thyroid extract, 20 mg. daily, from Oct. 21st until Oct. 30th, on which day it died. Weight at beginning of experiment, 620 grammes. The animal became dull and gradually emaciated. Weight at autopsy, 380 grammes. All intei-nal organs very much congested. The animal received a total of 180 mg. of extract.

No. II. Pig fed on the same desiccated thyroid as in the former experiments. Weight, 810 grammes. On Oct. 21st, one and a half pills administered; on 22nd, four pills; on the 23rd, the same quantity. The respiration had now reached 144 per minute. On the 24th, 2.5th and 26th, four tablets were fed daily, and during the night of the 26th, the animal died. At the autopsy the abdominal organs were found to be much congested. Weight, 620 grammes (loss 190 grammes). This animal received about seven grammes of the dried thyroid gland, or less than one per cent. (.864j of its bodily weight to produce a lethal effect.

No. III. Fed on desiccated thyroid tablets. Weight, 580 grammes. Oct. 21st, one pill ; on 22ud, three tablets ; on the 23rd instant, four; on the 24th, 25th and 26th, the same; on the 27th instant, six pills; on the 28th, four tablets; on the 29th, five ; on the 30th, five. The animal had been for several days very dull and had rapidly emaciated. The exitus took place on the morning of the 30th instant. At the autopsy the viscera were found to be much congested. The weight was 320 grammes. Loss of weight during the nine days of the experiment, 260 grammes. The animal received more than 2 per cent, of its weight in the dried gland to produce dissolution.

No. I\". The same thyroid preparation fed. Weight at beginning of the administration, 610 grammes. On Oct. 22ud, two tablets were fed to the animal ; on the 23rd, three ; on the 4th, four pills; on the 26th, six pills; on the 27th, four pills ; on the 28th, five pills. The pig has become very dull and does not take care of its fur. Died Oct. 30th. At the autopsy the animal weighed 370 grammes (loss, 240 grammes) and the viscera were much congested. This animal received 1.30 per cent, of its bodily weight of the gland to cause death.


No. V. Thyroid dog (Dr. Abel). Thyroid gland extirpated i)i loto in Oct. 1895 ; died one year later, after showing profound emaciation and a dermatitis suggestive of myxoedema. At the autopsy several parathyroid bodies the size of a small pea were discovered. This animal was fed for several mouths on thyroids and thyroid extracts, seemingly without benefit. The autopsy showed no demonstrable lesions.

The guinea-pig series may be looked upon as an example of the acute type of poisoning by the administration of thyroid gland, while the mice are of a more chronic order. It is impossible to estimate the exact percentage necessary to produce lethal results with the mice, for the reason that these small animals always left some crumbs of the tablets on the floor of their cages which it was not practicable to collect. The guinea-pigs on the other hand were fed with the entire pill without loss, and but in one case was less than about one per cent, of desiccated gland found to produce lethal results, the administration being distributed over five days.

The microscopic examination of the cerebra of the eight mice and guinea pigs showed, both with the silver phospliomolybdate, and aniline and hematoxylin stains, an absolutely normal condition of the nerve elements and neuroglia ; none of the varicose and atrophied dendrites, with loss of the gemmulffi, of the former studies being discovered. The corpora retain their angularity and sharp outlines, and the axons with their appendages, the collaterals, retaining their natural appearances. The sections stained with anilines and hematoxylin showed the normal appearances of the nucleus and nucleolus, and not even in the tunics of the blood-vessels, where pathological changes were most carefully sought for, could any demonstrable lesion be discovered.

The nearest approach to any pathological condition found was in the cerebrum of the dog that had had its thyroid gland extirpated a number of months before death, though even here the lesions were confined to a very few tumefied dendrites, a condition that was most probably caused by the long continued state of mal-nutrition into which the animal had fallen.

More particular attention was paid to the examination of the liver than to the other organs of the abdominal cavity, but here again we failed to find more than a turgescence of the blood-vessels, the liver cells retaining their natural characteristics.

It is obvious from these results that the death of the various animals was induced by an entirely different kind of intoxication than that causing the lesions of the nerve elements in riciu and alcohol tox£emias, and it is therefore a poison that does not induce degenerative alterations in the sheaths of the arteries, and the consequent disturbance of the nutritive supply, followed by pronounced changes in the neurons, dependent to a certain degree upon the intensity of the vascular lesions; but acts upon the general system in an entirely different manner, and is essentially more subtle in its effects upon the nerve tissues, corresponding more to the action of a group of chemical poisons that leave no trace of their effect after death upon the nerve cell, but during life inducing symptoms directly referable to the central nervous system. The tissue metabolism induced by the action of these poisons upon the nerve cell we can only at present conjecture.


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FIVE SUCCESSFUL CASES OF GENERAL SUPPURATIVE PERITONITIS TREATED

BY A NEW METHOD.*

By J. M. T. Finney, M. D., Associate Professor of Surgery, The Johns Hopkins University.


Recovery following laparotomy for piiruleut peritonitis is nufortunately of sufficient rarity to excite interest whenever it occurs. My object in making this report to the Society is two-fold ; first, to record five successful cases of laparotomy for general suppurative peritonitis, all treated by the same method; and second, to describe briefly the method itself. The principle involved is not a new one; only in the manner of carrying it out is there any originality claimed.

Since the appearance in 1877 of the classical work of Wegner, and later that of Grawitz and others, it has been known that the healthy peritoneum is capable of disposing of a considerable amount of infectious material. J. G. Clark, in a recent article,f reviews the literature of the subject and gives the conclusions reached by the experimenters in this direction. All agree that the peritoneum is able under favorable conditions to take up a relatively large amount of infectious material and disjjose of it effectually. These observers were dealing with a more or less healthy peritoneum. On opening the abdomen of a patient suffering from general suppurative peritonitis, however, we have very different conditions with which to deal. The observations of Pawlowsky would indicate that the lymph channels leading from the peritoneal cavity are choked with infectious bacteria and inflammatory products in purulent peritonitis, and that thus the efficiency of the peritoneum would be greatly impaired. Our observations clinically seemed hardly to bear this out.

The question that suggested itself to our mind was this, whether or not the peritoneum, even under these most unfavorable conditions, still retained its absorptive power. It seemed to us, from our experience in operating upon such cases by the methods heretofore employed, that they were inadequate and did not remove a sufficient quantity of the exudate, but left the peritoneum little better off than before. With this idea in mind we devised a plan of treatment which, so far as we know, has not been employed elsewhere.

The steps of the operation are as follows : Make a sufficiently long incision to admit of easy access to all parts of the peritoneal cavity. Quickly withdraw the coils of small intestine from the peritoneal cavity, beginning with the worst coils first. Remove all, or as much as is necessary of the small intestine and place it outside the abdomen, covered with warm gauze or towels, thus practically disemboweling the patient for the time being Then thoroughly and systematically wipe out the peritoneal cavity with large pledgets of gauze wrung out of hot salt solution, paying particular attention to the pelvic portion. In some cases it may be well in addition to flush out the cavity with warm salt solution, but this is rarely necessary.


  • Read before the Medical and Chiriirgical Faculty of the State

of Maryland at its Annual Meeting in Baltimore, April 27, 1897. tBuUetin of the Johns Hopkins Hospital, April, 1897.


Next the small intestine should be systematically examined loop by loop while still outside the abdomen, and rendered macroscopically clean by wiping with gauze comjiresses wrung out of hot salt solution. It is necessary to wipe with considerable force at times, in order to remove adherent flakes of partly organized lymph. It should be done thoroughly and conscientiously, however, as upon this depends, we believe, in great measure, the success of the operation. It facilitates the cleansing process, as well as lessens the shock of the operation, if the wiping of the intestinal coils is carried on under a constant irrigation of warm salt solution.

After being cleansed macroscopically of all foreign material, pus, feces, lymph, etc., the intestine should be replaced in the abdomen — the worst or sutured coil being the last, or most superficial, in order that it may be the better drained by being packed about with gauze, if necessary.

The abdominal wound is then tightly closed, leaving just room enough between two sutures for the gauze drain. If there are any evidences of distension or pain the abdomen should have the Paquelin cautery thoroughly applied, and the bowels moved early by calomel in broken doses, followed by salts and a turpentine enema.

It is not claimed for this method that it will cure every case of general suppurative peritonitis. We believe, however, that a larger percentage of cases will recover after this method than any other with which we are familiar.

To insure success with any method it is essential that the operation should be performed within a few hours after the perforation has taken place. This is well brought out in the very interesting series of experiments on dogs made for me by Messrs. Elting and Calvert of the Johns Ilojikins Medical School, a report of which is subjoined.

Five cases have been operated upon by this method up to date, all of which have recovered. The first case, a case of perforating typhoid ulcer, has already been published,* and hence only a very brief abstract of the history will be given here.

Case I. — Male, aged 47, on about eighth day of mild attack of typhoid developed symptoms of perforation. Entered hosijital 14 hours later and was operated upon immediately. Peritoneum everywhere intensely congested, roughened and dull, and covered with flakes of plastic lymph. Considerable amount of turbid purulent fluid in abdominal cavity. Perforation in ileum about 14 inches from ileo-c;ecal valve. Fecal matter exuding from opening. Peritoneum cleansed in the manner described, gauze drainage. Recovery.

Case II. — G. W., male, aged 20. Saw patient for the lirst time, November 24, 1896, in consultation with Dr. Barringer in Charlottesville, Va. Patient gave history of four previous mild attacks of appendicitis, from which he liad promptly


  • AnnalB of Surgery, March, 1897


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recovered. The night before he had eaten very heartily of apples. He was awakened about 3 a. m. with severe abdominal pain, cramp-like in character. At about 6 a. m. Dr. Barringer was called. He stated that at this time, three hours after the beginning of the attack, the patient presented the classical symptoms of peritonitis. When I saw him, 24 hours later, he had a temperature of 103° and a pulse of over 100, and from the first had suffered intense pain, which was controlled only by morphia hypodermically. He had had nausea and vomiting all day. Examination of the abdomen showed slight distension and great rigidity of the abdominal muscles. A slight tumefaction could be made out just to the inner side of the anterior superior spine of the ilium on the right side. Tenderness very marked. Immediate operation advised and agreed to. Incision 5 inches long in right linea semilunaris. On opening the peritoneal cavity the intestinal coils in the right lower quadrant of the abdomen were found to be congested and dull and covered with flakes of adherent lymph. Elsewhere the intestinal coils were found to be congested, but not otherwise much changed in appearance. The pus, of which there was perhaps 200 cc, was not walled off, but everywhere present in pockets between the adherent intestinal coils. The appendix was readily found. It was closely adherent to the pelvic brim on the one side and the csecum on the other. Its distal end was swollen and distended to the size of my thumb, perforated and gangrenous over an area about as large as a five-cent piece. Appendix was ligated and excised, and stump covered with peritoneal cuff and suture. The peritoneum was treated in the manner above described. Recovery.

Case III. — This patient was seen first on December 14, 1896. His history is in brief as follows : R. S., male, aged 33 years. Has had no previoiis similar attack. The night before he was taken sick he attended a banquet and ate heartily of solid indigestible food. He was attacked with severe abdominal pain about 3 o'clock the next afternoon. The pain at first was general and cramp-like ; nausea and light vomiting during the night. Morphia was necessary to relieve him. The next day he was unable to get up. Toward evening his physician gave him a cathartic, after which the bowels moved 8 or 10 times in quick succession. The next morning the pain had shifted to the right side and was severe. He received a hypodermic of morphia and got on fairly well until about 6 p. m., about 60 hours after the onset of the attack, when he was taken with a sudden severe pain in the lower right side of the abdomen. The pain for a time was excruciating at the base of the penis. Vesical and rectal tenesmus marked. When I saw him, about 4 hours later, in consultation with Dr. Reiche, he had a temperature of 105° and pulse of 150, profoundly collapsed. I have never seen such a hard and retracted abdomen as he presented. His condition appeared grave. Immediate operation advised and consented to.

Incision about 5 inches long, in right linea semilunaris. On opening abdomen the intestinal coils were fol^nd not to be distended but considerably congested. Beginning in the right lower quadrant there was found a considerable amount of thin pus containing flakes of lymph. This condition


extended over into the left side, down into the pelvis and up into the hypogastric region. The appendix was found to be gangrenous and perforated, and was removed. The toilet of the peritoneum was made in the manner already described, by disemboweling and vigorously scrubbing the parietal and visceral peritoneum until macroscopically clean. The intestinal coils were then replaced, a gauze drain inserted, and the abdominal wound closed except a small opening for the drain. He made an uninterrupted recovery.

Case IV. — M. B., boy, aged 10. Operation by Dr. J. C. Bloodgood, January 7, 1897. Five days before admission to the hospital was struck in the abdomen by the fist of a playmate. Next day felt severe pain in the right iliac region. This progressively increased for three days, when vomiting began and the pain became general. Two days later was brought to the hospital, when his condition was found to be in brief as follows: Temperature 101°, pulse 128 and fairly good. Slight abdominal distension. Muscular spasm marked on right side, present but less marked on the left. General abdominal tenderness. Under ether a definite tumefaction could be made out in the region of the right kidney. This proved to be an abscess behind the cjecum, extending from the iliac fossa below to the liver above, and in this cavity was the diseased appendix. There was foiind no walling off of this from the general peritoneal cavity. The entire pelvis was filled with yellow pus and all the intestinal coils were covered with flakes of fibrin. The stomach and spleen were not seen, but the surface of the liver looked exactly as if it had been covered with yellowish-white paint. The appendix was removed and the entire abdominal cavity thoroughly wiped out with gauze pledgets wrung out of salt solution. The exudate was scrubbed oS the livers surface, after which it looked simply congested. A gauze drain was inserted and the abdominal wound partly closed. He made an uninterrupted recovery. Cultures and cover-slips from the peritoneum showed colon bacillus and a coccus (not differentiated).

Case V. — R. S. P., aged 9, a schoolboy, entered the Johns Hopkins Hospital, Feb. 26, 1897. He had always been healthy except for measles, whooping cough and chicken-pox.

Family history good except remote cases of tuberculosis on both sides.

Just 48 hours before entering the hospital first complained of pain in abdomen. Three hours later had an attack of vomiting. Pain in abdomen was at first general, but in a few hours became localized in the right iliac and lumbar regions. After about 24 hours the pain lessened somewhat, and he sat up for a little while, but shortly after pain and vomiting returned with increased severity. A physician saw him after about 36 hours and gave him calomel in broken doses. His bowels moved twice. His condition did not improve, and by advice of his physician was brought to the hospital at 8 p. m., 48 hours after the onset of the attack. His condition then was as follows : Face flushed and anxious. Pulse 126 ; temp. 102.8°; resp. 56, and entirely thoracic; abdomen generally distended and tender, especially in right iliac fossa, where the tenderness is extreme and muscle spasm very marked. Pain is most marked here also. Liver and spleen not palpable. Liver dullness on right corresponds about to costal border.


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Percussion over right iliac and lumbar regions shows dullness; tympanitic over left side. Heart normal. Fine moist rales over bases of both lungs. No history of any similar previous attack.

Diagnosis. — Perforating appendicitis with beginning general peritonitis. Immediate laparotomy advised and agreed to. Ether. When thoroughly auassthetized, a small, hard mass, somewhat movable, could be felt just over the middle of Poupart's ligament. An incision about 15 cm. long was made parallel to and over the right linea semilunaris. After exposing the peritoneum and before opening it several bubbles of gas could be seen free in the peritoneal cavity. On opening the peritoneum a considerable amount of thin, cloudy seropuruleut fluid escaped and some gas. The mass felt before was found to be the appendix with a roll of omentum adherent. The intestines, especially the CEecum, were distended and congested, and covered with flakes of fresh fibrinous exudate. The congestion was most marked in the immediate vicinity of the appendix.

The appendix itself was superficially placed and freely movable, not walled off, but had a portion of omentum adherent. It was rather long, and curled upon itself, with a constriction at about the junction of its proximal and middle thirds. It contained two concretions, the larger of which was engaged tightly in the constriction, and from this point to the tip the appendix was gangrenous and softened. A


small perforation was present at the distal end of the dateseed like concretion. 'I'here had been an apparent attempt of the omentum to surround the entire gangrenous end of the ajjpendix, but it had not quite succeeded. The appendix together with the adherent omentum was ligated and excised.

Pelvis was found to be full of pus, and the peritoneum treated as above. He made a rapid and complete recovery.

Bacteriological examination of the peritoneal exudate showed the presence of streptococcus, staphylococcus, and bacillus coli communis.

NoTK. — Since reading the above article, I have operated upon one additional case of general peritonitis. The patient, a young woman, was in extremis at the time of the operation, which was undertaken simply as a forlorn hope. This operation was secondary to one performed several days previously by another surgeon for appendicular abscess. There was found present a general peritonitis, with much jjlastic lymph covering the greatly distended and adherent coils of intestine. There was very little purulent fluid in the abdomen. Her pulse was very rapiil and thready, and her temperature had risen several degrees. After the operation she was placed in a continuous bath, which added greatly to her comfort. The operation seemed to prolong her life, as she lived about thirtysix hours following it.


AN EXPERIMENTAL STUDY OF THE TREATxMENT OF PERFORATIVE

A NEW METHOD OF OPERATION.

By Arthur W. Elting and William J. Calvert.


'ERITONITIS IN DO(iS BY


[From the Anatomical Laboratory of the John) Hopkins University.']


At the suggestion of Dr. Finney and with the permission of Prof. Mall, the writers have undertaken an experimental study of perforative peritonitis in dogs, with especial reference to the method of treatment of this disease in human beings, introduced by Dr. Finney. Inasmuch as this is a preliminary report, the literature upon the subject will not be considered. It may be mentioned, however, that so- far as we know no previous work of this nature has been done from a surgical standpoint. It was decided to divide the series of experiments into four groups :

1. To scrub the intestines of a series of normal dogs and study the condition of the abdominal cavity at varying lengths of time after the operation, in order to determine the results of the mechanical irritation.

2. To determine how long it takes a perforative peritonitis to destroy life.

3. To perforate the intestines of a series of dogs, and after varying lengths of time to operate upon them again, closing in the perforation and cleansing the abdominal cavity and the surface of the intestine and mesentery, and after variable periods of time to kill the dogs which recovered, and study the condition of the abdominal cavity.


1. To perforate the intestines of a series of dogs, and after varying lengths of time to close in these perforations without removing from the abdominal cavity any of the exudate or foreign matter present, and to study the results of this operaation.

The dogs used in these experiments varied in weight between 18 and 53 pounds, most of them weighing about 25 pounds.

For the first group of experiments four dogs were used. By a median incision the abdomiiuxl cavity was opened, the intestine and parietal peritoneum were vigorously scrubbed with gauze sponges wrung out in warm normal salt solution, and kept covered with warm towels. After this treatment numerous minute hemorrhages caused by the scrubbing were noticed over the peritoneal surfaces, and the intestine presented an extremely congested appearance. It was then thoroughly irrigated with warm normal salt solution, which had a marked effect in reducing the congestion. The intestine was then replaced in the abdominal cavity and the wound closed. The process of scrubbing as performed by the operator and an assistant required from 8 to 12 minutes. In every case the dog appeared ill for about 24 hours after the operation, after


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which a marked improvement in the condition was noticeable. Usually by the end of the second day the animal seemed quite well.

Of these four dogs one was killed by an accident one day after the operation. Autopsy showed a very small amount of blood-tinged serum in the abdominal cavity. The surface of the intestine and parietal peritoneum presented numerous hemorrhagic areas caused by the scrubbing at the time of operation. The surface of the intestine was roughened, though not adherent. Cultures from the abdominal cavity were sterile.

A second dog was killed at the end of three days. At autopsy no appreciable amount of fluid was found in the abdominal cavity. Numerous fibrinous adhesions of the coils of intestine to each other, to the inner surface of the abdominal wound and to the omentum were found. The surface of the intestine was slightly roughened and presented numerous hemorrhagic areas. Similar areas were also seen upon the mesentery near its attachment to the intestine and upon the parietal peritoneum. These were likewise caused by the scrubbing at the time of operation. Cultures from the abdominal cavity were sterile.

A third dog which was in excellent health and condition was autopsied at the end of five weeks. No appreciable amount of fluid was found in the abdominal cavity. The appearance of the organs was everywhere normal except for numerous adhesions of coils of the intestine to each other, to the omentum, to the inner surface of the abdominal wound and to the stomach. These adhesions were of a firm character, being apparently composed of fully developed connective tissue. Cultures from the abdominal cavity were sterile. The fourth dog is still alive and will be autopsied later. From this group of experiments we conclude that mere mechanical irritation may cause the formation of extensive adhesions in the abdominal cavity of the dog, but these seem in no way to seriously interfere with the animal's general health.

For the second group of experiments four dogs were used. Because of its accessibility and the comparative ease with which the perforation could be closed, it was decided to perforate the CEBCum. By the use of a stick of caustic potash a perforation IJ cm. in diameter was made in the end of the caBcum, after which it was replaced in the abdominal cavity and the abdominal wound closed. These dogs showed symptoms of a severe peritonitis and died in from 12 to 20 hours from the time the perforation was produced. Autopsy showed practically the same pathological condition in each case. From 150 to 250 cc. of a turbid bloody fluid were found in the abdominal cavity. The surface of the intestine presented a marked hemorrhagic condition, both diffuse and petechial in character. The omentum, mesentery and parietal peritoneum presented a similar appearance. Flakes of reddish yellow lymph were deposited over the surface of the viscera, particularly in the region of the liver, diaphragm and lesser omentum. Slight fibrinous adhesions between the coils of intestine were noted. The mucosa of the intestine presented more or less of a hemorrhagic appearance, and in some of the cases bloody contents were found in the lumen of the gut. In short, the pathological condition was one of an intense hemorrhagic


peritonitis associated with a more or less extensive hemorrhagic enteritis. The bacteriology of each of these cases was carefully worked out and will be referred to later.

For the third group of experiments twelve dogs were used. The method of operation was as follows: An incision was made on the right side just outside the rectus muscle, the cajcum brought out and perforated in the same manner as practiced in the experiments already described. The cajcum was then replaced in the abdominal cavity and the abdominal wound closed. From five to seven hours after the perforation was produced these dogs were again opened by an incision in the median abdominal line. The perforated end of the crecum was brought out and the perforation closed by means of a row of mattress sutures, after the necrotic tissue at the seat of the opening had been resected. The abdominal cavity was then opened, and the intestines being lifted out, were kejit carefully covered with towels wet in warm normal salt solution. With gauze sponges wrung out in this solution the surface of the intestine and mesentery was carefully wiped till it appeared macroscopically clean. The abdominal cavity was next wiped out and rendered macroscopically clean, the intestine in the meantime being frequently irrigated with warm salt solution and kept covered with warm towels. After another thorough irrigation of the intestine with the warm salt solution it was replaced in the abdominal cavity and the wound closed in the usual manner. We cannot emphasize too strongl}', in doing these experiments, the advisability of thorough and constant irrigation of the intestine while it is outside the abdominal cavity, for in every case it seemed to reduce the congestion and in some cases the distension. The cleansing process required from 10 to 20 minutes according to the amount of exudate and foreign matter present.

Of these 12 dogs one was operated on at 5 hours after the perforation was produced, one at 5J hours, one at 5J hours, one at 6 hours, two at 6J hours, three at 6J hours, one at Gi hours, one at 7 hours, and one at 7} hours.

In every case the dog showed marked symptoms of peritonitis and evidences of pain. When lying down the legs were drawn toward the abdomen, which was held very tense. Any attemjjt to straighten out the legs seemed to cause great pain. In some cases the dog vomited a somewhat bile-stained fluid. In every case the abdominal cavity at the time of the second operation contained from 100 to 250 cc. of a turbid bloody fluid. The intestine, mesentery and omentum in nine of these cases presented a generalized hemorrhagic condition. In the remaining three cases this condition seemed more confined to the coils of intestine in the region of the ctecum, though all the peritoneal surfaces seemed more injected than normally. In nine of the cases more or less numerous flakes of yellowish red lymjih were found adherent to the gut, mesentery, greater and lesser omentum and other abdominal viscera. In eight of the cases the intestines seemed more or less distended when replaced in the abdominal cavity. Immediately after the cleansing of the surface of the intestine and the abdominal cavity the animals seemed to be much more comfortable, and in the Ciise of every dog which recovered there was a jirogressive improvement in the condition.

In no instance did a dog which recovered show signs of


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pain after the cleansing operation was performed, and usually in from two to three days the dog seemed to have recovered completely from the peritonitis, so far as external symptoms would indicate. Of course the abdominal wound made at the second operation was infected, and this in nearly every case failed to heal by first intention, which delayed somewhat the complete recovery of the animal. Of the 12 dogs thus treated three died without any apparent beneficial effect of the operation, death ensuing within 20 hours from the time the perforation was produced. These three dogs were operated upon 64, 7 and 7} hours respectively after the perforation was produced. A fourth dog operated upon GJ hours after the perforation died 30 hours later; the operation apparently prolonged its life about 20 hours. In three of these cases the peritonitis was the most severe we met with in our experimentation, and the dogs in a weak condition at the time of operation, which was done comparatively late in the disease. In each of these four cases the intense hemorrhagic peritonitis described under the second group of experiments was found at autopsy.

The remaining eight dogs were apparently cured of the peritonitis. Of these eight, one died from the protrusion of the intestine, due to the breaking down of the abdominal wound on the fifth day after the operation. In a second case death resulted on the eighth day from a localized peritonitis due to the extension of the suppurative process from the abdominal wall. A third dog which appeared quite well 2i days after the operation died rather suddenly on the fourth day from a perforation in another portion of the intestine which had come into contact with the caustic potash upon the end of the perforated ca3cnm at the time the first perforation was produced. A fourth dog appeared quite well at the end of twelve days after the operation, having an excellent appetite and seeming very lively. On the 13th day the dog seemed sick, and gradually grew worse till its death, on the 17th day after the perforation was produced. At autopsy small abscesses were found extending along each stitch in the abdominal wall down to the inner surface of the wound, where the intestines and omentum were adherent. No distinct sinus leading into the abdominal cavity could be demonstrated. The abdominal cavity contained about 100 cc. of yellow pus, collected for the most part in the pelvis and also extending up toward the diaphragm. The coils of intestine and omentum were firmly adherent in a mass in the upper part of the abdominal cavity. The intestine was also adherent to the liver and gall bladder. The parietal and visceral peritoneum were intensely hemorrhagic in places. No apparent walling off of the pus existed. An extension of the suppurative process along the stitches was supposed to have been the source of the infectious material. A fifth dog also apparently made a complete recovery, both wounds healing with the exception of a small sinus in one of them. This dog seemed quite well for nearly three weeks, when it became ill and died three weeks and two days from the time it was operated upon. At autopsy the abdominal cavity presented a perfectly normal appearance, with the exception of numerous adhesions of coils of the intestine to each other, to the omentum, liver and parietal peritoneum. These adhesions were not very firm in character. The


sinus mentioned above was found to lead to an abscess cavity about the size of a hen's egg, situated in the pelvis to the right of the uterus. This abscess was completely shuf off from the rest of the abdominal cavity and was the undoubted cause of death.

All of these dogs which died as a result of the suppurative process following the operation would probably have recovered could they have been subjected to the same treatment human beings would receive in a similar condition, for it must be remembered that it is practically impossible to drain or treat suppurating wounds in dogs. A sixth dog, apparently in the best of health and condition, was killed and autopsied four weeks after operation. Both wounds had healed with the exception of a small sinus leading to a stitch abscess, which, however, did not penetrate the abdominal wall. On examining the abdominal cavity the only abnormalities noted were seven or eight slight, loose adhesions between coils of the intestine, three or four loose adhesions of the omentum to the intestine, and some rather firm adhesions of intestine to the inner surface of the abdominal wound over an area 3x6 cm. The condition of the viscera seemed everywhere normal. All of the adhesions, except perhaps those uniting the intestine to the inner surface of the abdominal wound, were of such a slender character that they would in all probability have disappeared entirely in a few months. The remaining two animals are apparently perfectly well, one of them being a bitch which was in a moderately advanced state of pregnancy when operated upon. Cultures and cover-slips were made from the exudate in each case of peritonitis. The bacteriology was carefully worked out and will be referred to later. From this group of experiments we conclude that up to 6 hours after perforation the generalized peritonitis in dogs can be cured by this operation in practically every case. The prognosis of operation upon these animals at 6i hours after perforation is exceedingly favorable, but from that time on rapidly becomes less favorable.

For the fourth group of experiments six dogs were used. The method of procedure in this group was to perforate the cfficum in the usual manner. From 6 to 6i hours later the abdominal cavity was again opened, the cfficum brought out and the perforation closed in the way before described. After the replacement of the ca3cuni the abdominal cavity was closed without in any way attempting to cleanse it. At the second operation four of these dogs presented a generalized peritonitis with the characteristics before described, though in no case did the condition seem as bad as in the cases of two dogs in Group 3 cured by the cleansing of the surface of the intestine and the abdominal cavity. Of these four dogs one died about 20 hours after the perforation was produced. The other three failed to rally after the second operation, as the dogs in Group 3 did, and appeared ill till their death two to three and one-half days from the time the intestine was perforated. Autopsy upon two of these animals showed an intense hemorrhagic peritonitis, while in the case of the third the intestine and omentum were closely adherent in a mass, which when pulled apart disclosed numerous pockets of pus, presenting the condition of multiple abscess formation. The remaining two dogs of this series presented only a localized


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peritonitis. Tliere was not more than half as much of the turbid bloody fluid in the abdominal cavity as found in the other four cases, and only those coils of intestine in the vicinity of the ca3cum presented a hemorrhagic appearance. These were the most favorable cases we met with in all our experimentation. These two dogs are still alive, though their recovery has been slow.

In connection with the last two cases it is interesting to note that in two of the cases of Group 3 some exudate had collected in the abdominal cavity between the time the intestine was replaced and the abdominal wound closed, thus making it evident that the abdominal cavity possessed the power of caring for a considerable amount of the exudate. The bacteriology of this group of experiments was also carefully worked out and will be referred to along with the reports of the other cases of peritonitis.

This group of experiments seems to demonstrate that the mere closure of the perforation, though it may in some cases prolong life slightly, is not sufficient to cure a case of generalized peritonitis in dogs, and makes it very evident that without a careful cleansing of the surface of the intestines and the abdominal cavity recovery in such cases will be exceedingly rare. It must be borne in mind that the length of time which had elapsed since the perforation was produced and the condition of the abdomiual cavity would have afforded a most favorable prognosis in these cases had the cleansing operation been performed.

Cultures were made from the 4 cases of Group 2, 13 cases of Group 3, and 6 cases of Group 4. In one case of Group 3 the cultures failed to grow, although cover-slips


showed a few cocci and bacilli. Also in one case of Group 4, in which the peritonitis was not yet generalized, the cultures were negative. In the twenty cases in which bacteria developed in the cultures, from one to three species of microorganisms were found in each case. Members of the colon group were found 18 times, 4 times alone and 14 times in association. Streptococcus pyogenes was found 8 times, once alone and 7 times in association. Staphylococcus albus was found 5 times, in each case in association. Staphylococcus aureus was found 4 times, once alone and 3 times in association, and staphylococcus citreus was found 4 times, in each case in association. Cultures were also made from the heart blood at several of the autopsies, but in each case were sterile. Coverslips from the exudate in the abdominal cavity were examined in each case and more or less numerous bacteria were seen. An abundance of leucocytes was found in nearly every coverslip. The bacteria in general were outside the cells.

From our experimental work we feel justified in stating the following conclusions :

1. That mere mechanical irritation of the peritoneal surfaces will lead to the formation of adhesions.

3. That peritonitis in dogs caused by a perforation of the intestine is of an intensely hemorrhagic character, and if left to itself rapidly proves fatal.

3. That generalized peritonitis of this character, in dogs, can be cured as late as 6* hours after the perforation, by the cleansing operation introduced by Dr. Finney.

4. That mere closure of the perforation without this cleansing operation will rarely, if ever, cure a case of generalized peritonitis in dogs.


SQUAMOUS EPITHELIOMA AND EPITHELIAL HYPERPLASIA IN SINUSES AND BONE

FOLLOWING OSTEOMYELITIS.


By S. M. Cone, M. D., Assisfcmt in Surgical Pathology, The Johns Hopkins University.


In view of the interest manifested in the pathology of bone, the two cases about to be reported seem to be of value. They are striking examples of malignant and benign epithelial growth into old sinuses and medulla of bone.

Case I. — John H., colored, set. 45, laborer, was admitted to Dr. Halsted's wards, January 2, 1897.

Patient gives a history of injury to bis left tibia 19 years ago, with subsequent formation of a sinus and discharge of sequestra. One month before entering the hospital the patient began to feel pain in the leg, and the odor of the discharge became foul. No sequestra have come away for eight months. There is pulsation of discharging material synchronous with the radial pulse.

Upon Jan. 4, Dr. Bloodgood excised the sinus aud chiseled and curetted the bone. The bone was fractured 10 cm. below the knee, where the cavity was largest. The operator's note estimates the cavity communicating with the sinus as 3 cm. deep, 2 to 3 cm. wide, aud 14 cm. long. The diagnosis, squamous epithelioma, being confirmed, and the growth


recurring withiu two weeks, the leg was amputated above the knee, and glands of the groin excised by Dr. Finney on Jan. 29th. On Feb. 25th patient was discharged, the wounds having healed per primam.

Pathological rejmrt of the first operation. — Tiie specimen consists of the skin, sinus, eburnated bone, and soft material filling the cavity in the bone. The edges of the sinus are dense and pearly in appearance. The skin within i cni. of the sinus edge has lost its dark pigmentation. The bone next to the soft central mass is soft and crumbly, but outside of this is eburnated. It appears directly continuous with the skin at the orifice of the sinus. The sinus is lined by the same papillary growth that fills the cavity in the bone, and this same growth projects between the periosteum and eburnated bone, indenting it, causiug a jagged appearance. The medullary cavity is filled with a soft, necrotic-looking material, made up of soft yellowish white masses, aud with white papillary granular projections from a rather dense translucent pink ground substance looking like granulation tissue. The papil


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lary projectious average 2 mm. diameter, aud are of varying length up to 4 mm. The growth within the cavity erodes the bone, leaving small spicules and granules in the soft necrotic mass. In places the dense bone has become granular and crumbles readily. There is no sequestrum nor cancellous bone. The periosteum is very much thickened aud not to be well differentiated from the subcutaneous tissue; it is invaded by the epithelial growth. The microscopical description of the original sections is the same as of the recurrent growth, so they will be included together.

The leg and lower third of the thigh removed at the second operation present no abnormal appearance outside of the gajiing granulating wound in the tibia, the seat of an osteotomy performed January ith. The wound, measuring 16s 4x4 cm., is surrounded by edges of skin inverted over the bone, which for the most part is covered by apparently healthy granulations. Only at one place is the bone exposed ; this is at the upper angle of the wound, where an edge of eburnated bone is left uncovered. At the outer rim of the excavated tibia, 4 cm. from the upper angle of the wound, is a projecting mass of papillary excrescences 4 cm. in diameter, whose surface is covered by a dry blood-stained crust. Scraping the up[)er layer away leaves the deeper papillae, pearly in appearance, closely aggregated and more or less intimately connected with the velvety granulations about them. Some of these epithelial uests are so closely packed without any apparent stroma that at first glance they give the appearance, on section, of a cheesy mass. Careful observation shows this to be made up of individual uests. This mass is at the seat of fracture alluded to. Similar uests of cells are seen iu smaller discrete masses over the whole surface in the granulations.

One area on the inner wall of the excavated tibia, 5 cm. from the uf)per angle of the wound and 2 cm. from the fracture, can be made out as a mass sharply defined from the surrounding granulations. The bone here seems excavated to fit the growth which is eroding it. Spicules of bone project into the growth between the epithelial plugs at the jjeriphery. Between the ends of the fracture the new growth projects, invading muscle and adjacent tissues. The ends of the bone are rough, and the papillary masses are seen indenting the ivory-like bone to a depth of 1 to 3 mm., giving it a wormeaten appearance ou removing the growth. The granulations, 2 to 4 mm. thick, covering the surface of the bone also groove it and cause a rough and gnawed appearance.

The bone sawn through at several places is dense aud eburnated aud shows no evidence of tumor formation which is not directly connected with the surface growth. The heads of femur, tibia aud fibula aud the astragalus are normal. The tibia and fibula are anchylosed by bony union at the interosseous ligament. No tumor can be traced from the bone along the vessels. The muscles and soft parts, except at the seat of fracture and ulcer edge, appear normal. The cartilage of the patella is softened, that over the outer head of the femur is depressed and soft. The synovial membrane is hemorrhagic where it envelops the crucial ligaments at their insertion into the head of the tibia.

The popliteal aud inguinal glands are firm, eularged and harder than normal, but do not show any areas of metastasis.


Microscopical Description.

Tumor iiivading musde at the seat of fracture. The tumor mass is sharply circumscribed. At that part nearest the invaded tissue the tumor is made up of single cells and small masses of cells in a fine reticulum; this passes, further away, into small non-cornified, non-cystic masses of cells, theu larger alveoli with cornified epithelium in the centre of the stratum mucosum layers. Furthest away from the muscle and nearest the periphery of the tumor mass are seen cystic dilatations with anastomosing alveoli lined by a few layers of columnar cells and containing scales of cornified epithelium aud fatty detritus. The invaded fibrous tissue shows no change. The muscle fibres are granular and fragmented ; the fragments and individual fibres contain many nuclei, giving the appearance of elongated giant cells. The vessel walls show round cell infiltration. There are newly formed capillaries among the degenerating fibres. There is evidence of endothelial proliferation in the capillaries.

Tumor mass and ski7i, the mass projecting betiveen the fractured ends of the tiiia. Where skiu and tumor pass over into one another the regular papills of the skin cease, as does the deep pigmentation. The pigment is no longer seen between the stratum mucosum cells as in the skin, aud is much less developed in the stratum granulosum and deepest columnar epithelium of the Malpighean layer.

It looks as if the stratum mucosum aud granulosum were continuous with like layers of cells lining the stroma of the tumor, keeping on over the tortuous papillary bulgings and corresponding depressions of the tumor mass. Similarly can the stratum corneum be followed, but it changes its appearance over the tumor, becoming less compact and scattered in flakes on the surface, or loosely filling cystic cavities along with cellular detritus, or it may be lacking on some of the plugs.

In the cornified layers over the tumor are masses of brown granular pigment containing crystals of hsematoidin. The tumor growth is divided by deep grooves caused by keratinizing and fatty degeneration of epithelial down-growths. This causes the follicular appearance described macroscopically.

Papillse, or stroma strands, better named, push the epithelium up into bulging papillary masses. These stroma strands vary in size, as do the corresponding cyliuders and plugs of epithelium lining them. The plugs aud cylinders anastomose freely at the surface. One cyst thus caused measures 1 X ^ cm. aud is made up of numerous small plugs containing keratinized epithelium and detritus around the margin. The contents must have fallen out in great part. The surface is covered with epithelial cells, polymorpho-nuclear leucocytes, and keratinized epithelium iu a mass of coagulation necrosis.

The stroma varies in different parts, from edematous young granulation tissue with stellate, epithelioid aud giant cells at the surface under the coagulation necrosis, to a very cellular fibrous tissue, with numerous capillaries aud spindle-shaped long nuclei deeper down. In places the stroma is homogeneous aud stains pink with eosin, like hyaline. There are areas of round cell infiltration in the stronui. The included plugs


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and cylinders of epiLhelinm comprise all the epidermis layers arranged in the same order as in the skin — a cylindrical or cuboidal layer next to the stroma, then polyhedral cells of the stratuna mucosum showing prickles most distinctly with Van Gieseu's stain, then two or three layers of spindle cells with pigment which takes the hEematoxyliu stain — the stratum granulosum. The outermost layer lining or filling the Ciivity of the plugs or cylinders is of loose keratinized epithelium, sometimes arranged compactly,

Where the centres are cystic we find besides the keratinized epithelial flakes, fat cells, cells which have undergone fatty degeneration, leucocytes and salts, granular and deeply stained with bajmatosylin. Cell multiplication is very active, as evidenced by the many divided and dividing nuclei ; 2 to 5 nuclei are contained in some cells, connected as if budding.

Tnto the basal layer of these cylinders there may be ingrowths of papilla?, explaining an unusual appearance, namely, a mass of fibres and connective tissue cells cut across in the centre of one of the above described plugs of epithelial cells. In the deepest part of the invading tumor the cylinders become very small, even narrowed to single cells separated by the same cellular stroma. Anastomosis is very free, many branches spreading throughout a loose stroma. The arteries included in the section show marked endarteritis and round cell infiltration of the adventitia also.

In staining the sections the Van Giesen method was found valuable in staining the stroma and the prickle cells. The keratinized cells stain yellow, the young stroma stains dull red. Gram's stain used for keratohyalin by Ernst' shows it well, staining these cells deep blue.

Sections of the pink granulations over the surface of the bone show granulation tissue without evidence of tumor.

The lymph glands of the popliteal space and groin show fatty atrophy and connective tissue formation, thickened capsules and endothelial hyperplasia. There are no metastases.

The popliteal artery and vein with surrounding tissue show no evidence of tumor growth about them. They are united by dense fibrous tissue. There is evidence of endarteritis.

The synovial membrane described as hemorrhagic shows round cell infiltration and vessels filled with blood, which also suffuses the surrounding tissue.

The bone cut across near the knee shows no microscopic evidence of carcinoma; it appears normal.

Section of fragments of hone with tumor and granulations mixed in an irregular friable mass. The tumor alveoli and stroma are as described above. Adjoining whorls are seen to become conglomerate, mixing together their contents of keratinized epithelium and fatty necrotic substances and bounding this by their several epidermis layers. Secondary papilla; project into the primary alveoli, giving a complicated appearance on section. In the proximity of the bone the cellular stroma is strewn with giant cells with centrally massed large oval vesicular nuclei containing big nucleoli. These are osteoclasts, for wherever the bone is seen undergoing absorption it is lacunar in nature and the Howship's lacunae contain osteoclasts to fit them. The tumor cells do not come in direct contact with the bone, being separated by stroma and osteoclasts.


The bone is very dense, with narrow compact lamella; containing few corpuscles, and these are small and far apart. The Haversian canals are filled with cellular connective tissue, vessels, old bone fragments looking as if shelled off, and osteoclasts in lacunaj. Branching canaliculi are distinctly seen. There is new formation of bone going on. The new lamellse are arranged at an angle to the old ones, they take the eosin stain deejier and are lined by osteoblasts, cuboidal and spindle-shaped. There is a granular line stained with hsematoxylin between old and new bone.

Section of hone zvith invading tumor at the seat of fracture. The lamellae are narrow and closely packed and enclose bone corpuscles at rather wide intervals. Some of the corpuscles nearest the invading tumor are enlarged and the cells are deeply stained. The Haversian canals are irregular in contour, of various sizes, and filled with granular detritus and fragments of bone. About their rim there is lacunar absorption, the grooves being small. The bone, where invaded, is being absorbed by the osteoclasts, for in every Howship"s lacuna can be seen a giant cell such as Kolliker' describes, or large osteoblasts which here take on the function of osteoclasts and are such.

These osteoclasts vary in size and shape, each fitting exactly a groove in the bone hollowed out to fit the absorbing agent. Some of the cells are seen completely surrounded by bone, others have only one-third of their body enclosed by the lacuna. The shape varies from oval, round, oblong, large cells to elongated flat cells lining quite a large part of the bone surface, looking almost as if one of the outer lamellae had broken off abruptly and taken in many large nuclei. The size varies from an osteoblast to cells five or six times as big.

The nuclei are either massed in the centre or arranged around the perijihery ; they are large, round or oval, and vesicular. The protoplasm of these osteoclasts is granular and stains deeply with eosin, especially at the centre. The edge of the cell next the bone is rough ; the other borders of some cells seem of double contour and quite smooth.

No foreign bodies were detected in any of these bodies next the bone, yet some of the giant cells near by included epithelial debris.

The protoplasm of some osteoclasts is drawn out like a pseudopod and pushes in between the connective tissue cells. Where granulations seem to fill the lacuna? one finds osteoclasts between them and the bone wall.

There is evidence of new bone formation. To the characteristics of newly deposited bone already mentioned can be added the closer approxinuitiou of bone cells — there being more of them than in the older adjacent bone. The medullary spaces between the cancel li of bone are filled with newly formed fibrous tissue and granulation tissue containing giant cells and all the cells usually found in embryonal tissue. There are also numerous capilhmes and larger vessels in the spaces. The bone cells vary in size and appearance, as do the bone corpuscles, some being round and spindle-shaped, others stellate. They can be best studied in the newly deposited bone or in bone undergoing absorption. It would seem as if when about to be freed from their imprisonment they take ou active functions again and are stained more readily.


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As in other sections of bone, no tumor cells come in direct contact with the bone. The tumor advances as described above. There are small fragments of bone in the granulations, which look as if they had been eaten off and left. There is a deposit of new bone in the vicinity of the tumor and evidence of absorption going on in the same microscopic field.

Case II.— W. J. R., white, a3t. 5i, admitted June 26, '95.

For 49 years the patient has had discharging sinuses in the thigh communicating with necrotic bone.

Operation, June 28th, by Dr. Bloodgood. Amputation of thigh at the upper third. Notes made at the operation refer to the great friability of the bone, the thickened periosteum, thin shaft and presence of a sequestrum.

Nov. '96. Patient reports himself well.

The pathological report is as follows : The diseased condition of the bone begins 26 cm. above the condyles and involves the shaft for 16 cm. The last jjiece of bone removed, 3 cm. below the trochanter, appetu'S healthy. The periosteum is thickened, the shaft, stripped of periosteum, is rough and presents minute spicules. The shaft varies in thickness from 3 to 6 mm., and there is very little cancellous bone. It is brittle, fracturing easily. The medulla above seat of disease contains much fat and oily material. At the seat of disease there is no involucrum. In the sinus leading from the diseased bone there is a sequestrum 6 cm. long and li cm. wide. The periosteum about the necrotic portion is 5 to 6 mm. thick, and on section is peai'ly white and appears striated at right angles to the long axis of the bone. On the surface nest to the shaft it is covered with a yellow necrotic friable tissue covering a leathery surface. Fine spicules of bone are imbedded in this. The odor is foul. The surface of the shaft is rough and hard. The medullary cavity is filled with hard bone mixed with thick leathery tissue, and is riddled with small cavities containing the same material as covers the shaft. The only attemjit at new bone formation is in the medullary cavity. No attempt at formation of healthy granulations is evident. About the area of disease the shaft exhibits exostoses 1 to 1^ cm. in length. The knee joint is normal in appearance.

Microscojiical examination of the tissue between the periosteum and bone described as striated and friable with necrotic border next to the shaft, shows it to be made up in the main of large swollen polygonal cells with oval vesicular nuclei. The arrangement is such as one sees in the stratum mucosum of the skin. There are papillas jirojecting into the mass from the periosteum, which is thickened and infiltrated with small round cells. The cells next the papilla} are prickle cells; those nearer the shaft do not show the prickles. The cells arc massed in varying density. According to the location of the papilla} we get lighter and darker stained masses, the darker being more comjiact and approaching the cancroid pearl in appearance, but there is no cornified nor degenerated centre. Toward the bone the cells are flat and the nuclei lose the ability to stain. A thin layer of cornification covers their surface. Many of the nuclei are vacuolated. The papilla are very cellular. There is an absence of the stratum granulosum and lucidum ; simply a uniform growth of the mucosum


and corneum. There is considerable endo- and periarteritis. The muscle and connective tissue show no tumor invasion. The leathery material described in the medulla is like that just described.

Examination of the cortical bone from the shaft shows no tumor growth into it. The dense bone presents a feathery appearance commonly seen in eburnated bone. The edges show lacunar absorption.

A number of cases of squamous epithelioma developing in sinuses antl old scars which would come under the grouping I have purj)osely omitted, since the pathological description of the tumor is in every case essentially the same as in Case I. Two of the cases might be considered carcinoma developing in osteomyelitic sinuses, but the history does not fully substantiate this. In these cases the sinuses were lined by the tubules and plugs of epithelial cells continuous with the tumor mass in the bone itself. The invasion of the bone resembled that described in Case I.

The cases reported bring to mind several most interesting subjects in pathological histology: the development of carcinoma in sinuses, scars and ulcers, its invasion of bone, the peculiar character of epithelial growth, and the bone formation and absorption due to the invading tumor. They are interesting especially because they show side by side the picture of a typical squamous epithelioma and a mere enormous hyperplasia of the epithelial elements of the stratum mucosum in bone. The one is evidently quite malignant; the other does not appear to be very destructive in its growth, but merely a filling in of the space made void by the osteomyelitic process. The two tumors have their homologues in the epithelial growths in sinuses, ulcers and scars, some being typical epitheliomata, others simply hyperplastic growths of epithelium lining the sinus walls.

There is this point to be noted in Case II differing from any yet described — the great development of the cells of the stratum mucosum to the exclusion of the granulosnm and lucidum. There is simply a single layer of cuboidal cells covering the papilte, then 10 to 15 layers of large swollen polygonal cells covered by a thin layer of cornified epithelium. This not only fills the sinus and medullary cavity, but pushes in between the periosteum and the shaft, nowhere penetrating the bone itself. It may be compared in a way with a case of great epithelial cell hyperplasia of the outermost layers of the epidermis described by Busch'" in a case of lupus. Here there was an epithelial papillary growth covered by thickened, horny epithelium spread over the surface, finally breaking into the connective tissue and forming carcinoma.

Typical squamous epitheliomata in scars, ulcers and sinuses are not uncommon. There are only twenty-eight cases reported in which the epithelioma developed in the sinus following osteomyelitis. From the histories of many cases of epithelioma in ulcers I infer that a few if more accurately described would come under the heading of carcinoma in sinuses following osteomyelitis. Some give a history of osteomyelitis. See Van Hook,' Schindler,' Boegchold." Borchers' iu 1891 collected all the cases up to his time, numbering twenty-five. He records cases of Konig, Dittrich,'" Nicoladoni," Esmarch, Fischer," Bartens, Coruil and Kanvier,'


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Winiwarter," Hauuover"^ and Volkmauu." Another case is recorded by Feigel.' One of Van Hook's' two cases was undoubtedly carcinoma developed in an old fistula communicating with necrotic bone. Von Friedlander's" three cases, reported in 1894:, are the last recorded. All of the cases described have many points in common with our first case.

Clinically, the development of the disease in those beyond 40 years of age, the common involvement of the lower extremities, the uncertainty of fixing the exact time of development, its slow growth, the foul odor, the long existence of the fistulaj, the absence of pain until the carcinoma begins to develop, the ease with which the bone is broken, the fixation of the neighboring joints and ankylosis of adjoining bones, the infrequent involvement of lymphatic glands or other organs, and its almost sure recurrence unless the limb be amputated, are all most noteworthy points.

Volkmann" says that recurrence occurs in a few weeks or months after the operation, if at all; if not Avithin 1 to Ih years, it seldom occurs.

The pathological picture is not to be confused with any known disease of bone or sinus. The crater-like ulcer or cauliflower excrescences made up of individual oval yellowish white masses, are enough to make the diagnosis. Finding the same papillary growths in the medullary cavity is not calculated to make one think of simple osteomyelitis. The bone next the tumor is either soft and spongy or denser than normal bone. It is increased in circumference and the medullary canal may be smaller than normal. Osteophytes may form on the surface and the bone may rarely present the appearance of spina ventosa. Fracture is common.

The microscopical picture is that of squamous epithelioma modified in appearance according to the amount of degeneration and bone absorption and the greater or less development of tubules, alveoli or cysts. The tumor cells nowhere come in direct contact with the bone, being separated by connective tissue and giant cells or osteoblasts. The thickness of the growth varies, but it is thickest in the cloaca, and in places looking like granulation tissue. The sequestra in Nicoladoni's" cases were not invaded by epithelial cells.

Borchers' refers to the advance of the tumor into the Haversian canals. Our cases do not substantiate this, the epithelial cells never being found separate from the main growth.

In none of the cases were metastases found in the internal organs and rarely even in the lymph glands. The swollen glands usually became of normal size after amputation of the limb. The reason of the infrequent metastases is found in the sclerosis and condensation of tissues about the tumor and its very slow growth.

Thinking of the etiology and histogenesis of the tumors, one would naturally class those described with tumors developing in ulcers, fistulas and old scars. Many theories have been advanced to explain them: Virchow's" idea of chronic irritation, mechanical and chemical, being most naturally first alluded to. The question whether the connective tissue growth or epithelial proliferation be the primary factor has been most actively debated since Ribbert" so strongly advocated the former view. Boegehold,* who reported several


cases like my first one, believes in their connective tissue origin, and says that the epithelium is lost over scars and ulcers. He says : " If the surface epithelium cannot cover over the granulation surface, one cannot see why it shall grow into the depths of the granulation tissue."

Langeubeck," in discussing the development of carcinoma in lupus, expresses the view that the cause of development is like that in traumatic scars, a continuoiis irritation and the carcinoma develops from remaining epithelial cells. It is distinct from the lupus growth. "It is difficult to reconcile the notion of lupus — a granulation tissue — passing directly into carcinoma, because of our view that epithelioma must come from pre-existing epithelial cells."

AVenk,"' who believes in this direct transition, concedes that the epidermis projections have not been entirely destroyed. Langenbeck"" attributes its formation to development of epithelium in the outlying scar. Schindler cites cases to prove the development from the scars — either from the covering epithelium or glandular organs of the skin left intact by the lupus process. He answers Boegehold's* argument cited above, by explaining that the surface epithelium is prevented from spreading superficially by continual irritation (pressure or secretion) and therefore it dips down deeply where not exposed to these influences. Hulke,'"' in describing two cases of carcinoma in old scars, ascribes them to purely local causes. Pedraglia^^ refers to old age and periodic irritation as predisposing causes. This view that old age influences the growth corresponds with that of Verneuil referred to by Marcuse:" "Ein locus minoris resistentiae" of the connective tissues, the epithelium retaining and increasing its activity. Marcuse uses this theory in explaining the growths in the granulations covering ulcers — the granulation tissue, when not going on to scar formation, being not so resistant to epithelial hyperplasia as normal tissues. Here the epithelium grows into the tissues as stated by Thiersch'"' in his most valuable contribution to the etiology of epithelioma of the skin.

It is not much disputed now that epithelium only forms from preformed epithelium and not from leucocytes or connective tissue cells. This materially aids the histogenetic study of these tumors. Whatever the cause, the practical lessons obtained from them are of much value to the surgeon, and one is not tempted to use tentative measures to stop a growth which he knows by experience and microscopical study to go steadily onward in its course until it is excised radically.

1. Van Hook, W. : Carcinomas arising in Inveterate Ulcers and in Ancient Sinuses. North Amer. Practit., Sept., 1890.

2. Schindler, J. : Beitrag zur Eutwicklung maligner Tunioren aus Narben. Inaugural Diss., Strassburg, 1885.

3. Borchers, F. : Ueber das Carciuom welches sich in alten Fistelgiingen der Haut entwickelt. Inaug. Diss., Giittiugeu, 1891.

4. Boegehold : Ueber die Eutstehung maligner Tumoreu aus Narben. Virchow's Arch., No. 88, p. 229.

5. Feigel, L.: Ein Fall von primiirem Ki-ebs der Tibia. I'rzeglad lekarski, Nos. 3G and 37, 1891.


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6. Cornil andKauvier: Journal de rAiiatoiiiie, 1SGIJ-G7, p. 277.

7. Erust, P. : Sfcudien iiber normale Verhornniig mit Hilfe der Gramscher Methode. Arch. f. mik. Aiiat. und Eutwickluugsgeschichte, Bd. 47, p. 669, 1896.

8. KoUiker: Die normale Kesorptiou des Kuocheiigewebes. Leipzig, 1873.

9. Ribbert: Miinchuer Med. Wocheusch., 1894, No. 17; Vircbow's Arcb., Bd. 135.

10. Dittrich : Prager Vierteljahresschrift, 1847, II.

11. Nicoladoni: Arch. f. klin. Cbir., No. 26, 1881.

12. Esmarcb: Langeubeck's Arch., XXII.

13. Fischer, S.: Zeitschr. f. Chir., 1881.

14. Winiwarter: Beitriige ziir Statistik des Carcinoms. Stuttgart, 1878.

15. Volkmann, Rud. : ITeber das primilre Krebs der Extremitiiteu. Volkmann's Sammlung klin. Vortrage, 1889.

16. Hauuover : Das Epitheliom. Leipsic, 1855-56.


17. V. Friedlander: Beitrag zur Kenntnissder Carcinomentwickelung in Sequesterhohlen und Fisteln. Deutsche Zeitschr. f. Chir., 1894.

18. Busch: Langenbeck's Archiv, XV, p. 48.

19. Virchow : Die krankhafteu Gescbwiilste, Bd. II, p. 487.

20. Langenbeck: Berlin, klin. Wochenschr., 1879, p. 329.

21. Wenk, L. H. : De exemplis nonnullis carciuomatia epithelialis exorti in cicatrice post lupnm exedentem relicto. Kiel, 1867. Reference from Schindler, see above.

22. Hulke, J. W.: London Medical Times, Vol. 1, 1873, p. 135.

23. Pedraglia: Vier Fiille von Epithelialkrebs anf alten Narben. Giessen, 1853.

24. Marcuse, J.: Deutsche Zeitschr. f. Chirurgie, Bd. VII, p. 550.

25. Thiersch: Der Epithelialkrebs, uamentlich der Haut. Leipzig, 1865.


ON THE BLOOD-PRESSURE-RAISING CONSTITUENT OF THE SUPRARENAL CAPSULE.*

By John J. Abel, M. D., and Albert C. Crawford, M. D.

[From the Pharmacological Laboratory of the Johns Hopkins University .'[


Both clinical experience and laboratory research have shown that the suprarenal capsule is an organ of vital importance.

Physiologistst have proved that a very small quantity of an aqueous extract of the medullary substance raises the blood pressure to a great height above the normal. It has also uuequaled power in reviving a poisoned heart. Gottlieb,J for example, has shown that it will revive the heart of a rabbit which has practically stopped beating in consequence of an intravenous injection of chloral hydrate.

Bates§ applied an aqueous solution to the eye and found that it exerted a marked vaso-constricting action. In numerous cases of congestion a small quantity dropped into the conjunctival sac brought about an immediate pallor, lasting for some time. According to this writer the extract is very useful in prolonged operations, for, when repeatedly applied, hajniorrhage is prevented and cocaine anfesthesia is in consequence indefinitely prolonged. As the result of his two years' use of the extract Bates concludes " that within the limits of its sphere of activity there is absolutely no other substance which can take its place."

Other experiments|| go to show that the aqueous extract is


•Read before the Association of American Physicians, May 6, 1897.

tSehiifer and Oliver, Journal of Physiology, xvi (1894) and xvii (1895); Szymonowicz and Cybulski, Wien. med. WochenBchrift, 18'JG, No. 6.

JArch. f. exp. Pathol, u. Pharmakol., xxxviii, 106.

§New York Medical Journal, Ixiii (189G), iiil .

||Foa and Pellacani, cited in Maly's Jahresb. d. Thier-Chemie, xiii, 129; M.arino-Zuco, ibid., xviii, 231 ; Gourfein, Rev. Med. de la Suisse Romande, Oct. 20, 1895; Compt. rend., cxxi (1895), 311314.


a powerful poison when injected directly into the circulation and may lead to fatal results.

The various extracts that have been used in these experiments were mixtures of unknown substances, and it is as yet an unsolved question whether the various actions at present ascribed to the gland are due to one and the same substance.

We are at present interested in the isolation of the bloodpressure-raising constituent, for in a purified state, separated from all other constituents, it might become a therapeutic agent of great importance.

On the chemical side but little advance has been made over Vulpian's* striking original contribution more than forty years ago. Vulpian observed that the juice expressed from the suprarenal capsule of many different animals behaved in a striking manner toward ferric chloride and toward solutions of iodine, giving with the former reagent an emerald green color, and with the latter a beautiful rose carmine tint. No other tissue of the body, so far as investigated by Vulpian, gave these reactions.

Virchowt substantiated Vulpian's statements, but added nothing new. A year after Vulpian's first announcement his second paper appeared in conjunction with Cloez,J verifying and extending his first observations and stating his failure to isolate the chromogenic substance or substances to which the above reactions are due.

Equally unsuccessful were Arnold§ and Ilolm.ji Kruken


  • Note sur quelqiies reactions propres i la substance des capsules

surrenales, Compt. rend., xliii (1856), 063-665. ■)■ Virchow'a Archiv, xii (1857), 481-483. X Compt. rend., xlv (1857), 340-343. § Virchow's Archiv, xxxv (1866), 64-107. II Journ. f. prakt. ('hemie, c (1867), 150.


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berg,* years after, repeated the work of Arnold and came to the conclusion that the chromogeu of the suprarenal capsule is a nou-volatile, nitrogenous and ferruginous organic acid which is probably related to the tnracin of the musophagidai and to chlorophyll. He assumed that the substance giving the green color with ferric chloride is not the chromogenic substance of Vulpian, but more likely pyrocatechiu accompanying the chromogen. Attention being thus attracted to the possible occurrence of pyrocatechiu in the suprarenal capsule, others took up the subject.

Brunnerf found that an alcoholic extract cau be made to give nearly all of the reactions of pyrocatechiu ; thus, it gives the well-known green color with ferric chloride, passing into a fine red on the addition of ammonium tartrate and a few drops of an alkali; it reduces silver nitrate at room temperature, and Fehliug's solution on boiling. The addition of an alkali soon causes it to take on a dark brown color, lead acetate gives a precipitate, sodium nitroprusside and very dilute ammonia give a wine-red color. All of the above reactions being given also by pyrocatechiu, Brunuer concluded that Krukenberg was right in his belief that pyrocatechiu is present in the suprarenal gland.

After the discovery of the blood-pressure-raisiug property of the suprarenal gland, B. Moore,J working in Schilfer's laboratory, came to the conclusion that Vulpiau's chromogen and the blood-pressure-raising constituent are identical. He based his ojjinion on the fact that chemical operations which destroy the color reactions by oxidizing the reducing agent appear also to destroy the blood-pressure-raising constituent. That the solubilities of the active principle are the same as those of the reducing agent appears also to support this opinion.

Fraenkel§ worked with residues obtained with the help of alcohol and acetone as solvents. These residues raise the blood pressure and do not contain pyrocatechiu, and on the strength of the ferric chloride reaction and its reducing power he concludes that the essential principle of the residue is a nitrogenous derivative of the o?'</(odihydroxy-benzene series.

According to Fraeukel both Krukenberg and Brunuer are wrong in their opinion that the suprarenal glaud contains pyrocatechiu. Fraeukel concludes, like Moore, that the bloodpressure-raising constituent and Vulpiau's chromogen are one and the same substance.

More recently still, Muhlmann|| has attempted to prove that the blood-pressure-raisiug constituent is a pyrocatechiu derivative. He asserts that on boiling fresh suprarenal capsules with dilute hydrochloric acid the active principle is decomposed and the pyrocatechiu which is split off may be taken up with ether. Miihlmann has not, however, furnished conclusive chemical proofs for his assertion. Both Miihlmann and Brunner might have settled this point by precipitating the supposed pyrocatechiu with lead acetate and analyzing the lead salt thus obtained. Pyrocatechiu may be preseut in


  • Virchow's Archiv, ci (1885), 542-591.

fSchweizer. Wochensclir. f. Ph.armacie, xxx (1892), 121-123.

} Journal of Physiology, xvii (1895), Pron. Physiol. See, p. xiv.

'i Wiener med. Blatter, 1896, No. 14-16.

II Deutsche med. Wochenschr., 1896, No. 26, 409-411.


small amounts in the gland, but no proof of this has yet been furnished.

There is therefore at present great diversity of opinion as to the chemical character of the blood-pressure-raising constituent of the gland.

Whatever the probability may be of the correctness of this or that view, it is to be noted that all of the above-named investigators have based their conclusions on reactions made with aqueous, alcoholic or acetonic extracts ; none of them have even roughly isolated a definite chemical comjiound. The subject is one of great diflBculty, and our own work is at jjreseut merely preliminary, but we have arrived at the following conclusions which we believe to be borne out by our experiments.

First, we have found by isolating the blood-pressure-raising constituent in the form of a benzoyl compound and decomposing it, that the active principle is a substance with basic characteristics and that it must in all probability be classed with the pyrrol compounds or with the pyridine bases or alkaloids.

Second, that pyrocatechiu caunot be split off from the isolated active compound by boiling with acids, as has been asserted.

Third, we have found that a carmiue-red pigment can be separated from the sulphate of the active principle without destroying its jiower to raise the blood pressure.

Fourth, iu addition to this, we have isolated from the crude benzoyl product a volatile basic body which fumes iu the air and which emits an odor very much like that of coniiue.

Method of Isolating the Active Principle in the Form of a Benzoyl Compound.

We have used sheep's glands in large quantity. The medullary substance of the fresh glands was scraped out, dried on the water-bath at 60° 0., ground up finely, and extracted with ether for several days until the fats and the substance known as Manasse's jecorin were removed. In this way a fine dry powder of a grayish white appearance is obtained, the aqueous extract of which is very active in raising the blood pressure.

AVith 100 grammes or more of this powder, representing one kg. in weight or about 1000 fresh glands, we proceeded as follows:. The powder is repeatedly extracted with warm water acidulated with a few drops of dilute sulphuric acid until the gland has yielded up all of its chromogenic substances, as tested by Vulpian's reactions. This aqueous extract is evajiorated on the water-bath to a small bulk, a large excess of strong alcohol is then added and the whole allowed to stand 24 hours, by which time the proteids have all settled out. The alcoholic fluid is then filtered and the greater part of the alcohol removed by distillation ; the remainder is driven off on the water-bath. The entire removal of the alcohol is necessary, and in order to avoid too great concentration of the acid fluid, which seems to destroy some of the active principle, water has now and then to be added. The brownish fluid when filtered gives all the well-known reactions characteristic of Vulpian's chromogeu, and on neutralizing the sulplmric acid we found the filtrate to be physiologically very active.


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This filtered fluid is next treated with the proper quantity of benzoyl chloride and sodium hydrate according to the Baumauu-Schotten method of forming a benzoyl compound. There results a tarry substance of a light yellow color which sticks to the sides of the separator funnel and which is collected and washed until the wash fluid no longer gives an alkaline reaction. It is next dissolved as far as possible in alcohol and the alcohol evaporated. The residue is then treated with ether, which takes up the greater part of it, the ethereal solution is filtered and the ether driven oft.

The residue, which is of tarry consistence and amber color, is taken up in strong alcohol from which all basic substances have been removed by distilling from tartaric acid. It is then boiled for two hours with animal charcoal previously well washed with purified alcohol. After filtration and the evaporation of the alcohol a considerable quantity of crystalline residue is obtained which is found to consist of the benzoyl compound of the active principle contaminated with other benzoyl derivatives and which we may call the crude benzoyl product. It is insoluble in water, alkalies or acids of ordinary strength, is soluble in alcohol, ether, glacial acetic acid and concentrated sulphuric acid.

It is of interest in this connection to note that benzoyl chloride effects the complete removal of the blood-pressureraisiug constituent from an aqueous solution. This is proved by the fact that the filtrate from the insoluble benzoate no longer gives the characteristic chemical reactions of the active principle, and that chemical manipulations no longer yield a blood-pressure-raising constituent. Indeed, an injection of a sufficient amount of the material left after the sodium benzoate and the excess of alkali have been removed, causes a sharp and sudden fall of pressure instead of a rise.

It was not until long after we had made use of benzoyl chloride as a precipitant of the active jjrinciple that we obtained access to Fraenkel's* pai)er. From it we learned that a syrupy substance is thrown out when benzoyl chloride is shaken uj) with a pyridine solution of an extract of the gland. Fraeukel did not succeed in crystallizing this benzoyl conijjound, nor did he attempt to decompose it in order to ascertain whether it was in reality a benzoate of the blood-pressure-raising principle.

Methods of Decomposing the Benzoyl Compound.

A quick method always used by us as a qualitative test is as follows : The compound is dissolved in as little concentrated sulphuric acid as possible, crushed ice is slowly added, and the benzoic acid which has been split off is shaken out with ether. On neutralizing the solution we found it to give the reactions characteristic of aqueous solutions of the medullary substance. We have not considered this method adapted to the decomposition of large quantities of the product.

Decomposition of this benzoyl product was effected by means of an alcoholic solution of sodium alcoholate, and also with strong hydrochloric acid and alcohol, but these methods were found to be less satisfactory in practice than the following, which is the method on which we now rely. The benzoyl compound is dissolved in glacial acetic acid, the solution


  • VVien. med. BliiUer, IS'Jti, No. 14-16.


heated to near the boiling point, and an equal volume of a 25 per cent, solution of sulphuric acid actively boiling is slowly poured into the hot acetic acid solution, the whole being shaken meanwhile. The flask is now attached to a back-flow condenser ami heated on a small flame for about ten minutes.

The solution is next diluted with water and allowed to cool, the benzoic acid, which has been thrown out, is filtered off and the rest is removed with the help of ether.

Mixed with the benzoic acid which has been removed by filtration is found a dark brittle substance which softens on the water-bath, and which we assume to be a benzoyl compound of unknown composition which was apparently unaffected by the dilute sulphuric acid. On dissolving it in concentrated suljjhuric acid and diluting with crushed ice, the resulting fluid gives none of the reactions characteristic of suprarenal extracts.

After decomposing the benzoyl product with hot dilute sulphuric acid and removing the benzoic acid thus split off, we next get rid of the acetic acid by repeated partial evaporations, taking care not to let the solution become too concentrated and thus perhaps injure the active principle. After the removal of the acetic acid the sulphuric acid is precipitated with the help of lead carbonate. The lead sulphate is removed and the filtrate is allowed to stand in vacuo over sulphuric acid until it has become of tarry consistency. It is then exhausted with ether, acetone and absolute alcohol in succession.

The residue is physiologically very active, and it gives all the reactions characteristic of an aqueous solution of the gland — a beautiful rose color on the addition of an alkali, a green color with ferric chloride, reducing silver nitrate, etc.

However, we are not yet dealing with a pure substance. If we neutralize an aqueous solution of the product thus obtained with a free alkali or with a carbonate of the alkalies, an overpowering odor much like that of coniiue is jierceived. As this odor passes that of pyridine seems to take its place. The basic substance thus liberated fumes in the air or when a glass rod moistened with hydrochloric acid is brought into its neighborhood. To remove this basic substance we made an aqueous solution of the active principle as above isolated, rendered it faintly alkaline with sodium carbonate and shook out with ether several times in succession. But this method does not remove all of the coniiue-like substance. To effect this we were obliged to make the active principle strongly alkaline with sodium hydrate before shaking out with ether. The aqueous solution, in consequence of the addition of the free alkali, takes on a deep red color, and carmine red flocks are thrown out. After the removal of the coniine-like substance with ether, the fluid containing the red flocks was acidulated with sulphuric acid and the carmine-red substance was filtered off". The clear filtrate, which was a pale straw color, was concentrated in vacuo, and the active priuciiile taken up in weak alcohol. On account of the insolubility of the sulphate of the active principle in absolute alcohol it is difficult to obtain this entirely free of sodium sulphate. We hope in future to remove both the coniine-like substance and the pigment with the help of ammonia. The presence of pyridine in our ammonia prevented our using it for this purpose.


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[No. 76.


This volatile base of a coniine-like odor has not hitherto been described as a constituent of the suprarenal capsule. The beautiful carmine-red pigment we take to be identical with the red substance which many other observers have found to be thrown out as a precipitate when ammonia is added to a concentrated aqueous solution of the gland, or when a solution is evaporated in the presence of lead acetate.* Others have believed this red precipitate to be the oxidation product of the active principle of the gland, but we shall presently see that the active principle is still present in the filtrate from the carmine-red body. We have as yet made no experiments with this pigment except to note that it is but slightly soluble in dilute alkalies and insoluble in dilute acids, and that iodine destroys the color. Our method appears to make the further study of this substance possible.

The coniine-like substance we have secured in the form of its hydrochlorate, and with it we have made certain studies which will be published at a later date.

Chaeacteristics of the Blood-Pressure-Eaising Constituent AS obtained by decomposing its Benzoyl Compound.

We have now obtained the active principle in the form of a sulphate. As thus far isolated it is a hygroscopic, strawcolored residue which tends to crystallize on standing over sulphuric acid, agglomerates of small crystals forming on the edge of the bowl and the entire residue taking on a semicrystalline appearance. This sulphate does not contain the volatile coniine-like substance, nor do we find the carminered pigment which falls out on the addition of an alkali. Alkalies no longer liberate the coniine-like substance, nor do they throw out the red pigment, but they cause a brownish discoloration, and on heating, alkaline vapoi's, probably ammonia, are given off.

Our sulphate is very active physiologically. A small quantity suffices to raise the blood-jjressure as seen in Fig. 1, and it is therefore evident that we have isolated the active principle but slightly contaminated with other substances.

A final product even more active in small quantities is that whose action is shown in Fig. 2, where the mercury is driven out of the manometer. This more active compound still contains much of the coniine-like substance, and at once throws out the carmine-red pigment on the addition of alkalies. The sulphate of the coniine-like substance does not, as we have seen, raise the blood pressure; it therefore remains for us to consider whether the carmine-red substance which is precipitated on the addition of alkalies, either alone or in conjunction with small quantities of oxidizing agents, has any j)hysiological significance or stands in any chemical relation to the blood-pressure-raising constituent. We incline to the opinion that this substance, which in the original aqueous solution of the gland gives with iodine water the " teinte rose-carmin tout a fait remarquable" of Vulpiau, is in nowise connected with the blood-pressure-raisiug constituent. We have repeatedly removed or destroyed this substance by boiling solutions containing it with strong ammonia or with sodium

•Holm, Journ. f. prakt. Chemie, c (1867), 150.


hydrate, and have always been able to separate subsequently an active material. In proof of this we append Fig. 3, showing a great rise of blood pressure, although the material from which this active principle was obtained had been boiled for one hour with a 5 per cent, solution of sodium hydrate. After such treatment with alkalies, care must be taken in the subsequent evaporation of the alcohol with which the active principle is removed, to keep an acid reaction, as otherwise the greater part, if not all of it, will be destroyed by oxidation. And unless all evaporations are carried on under reduced pressure, much material will be lost, even with the above precaution.

Although somewhat contaminated with its own decomposition products, this final sulphate has all the characteristics of an active substance. As shown by repeated experiments, it promptly raises the blood pressure, it constricts the vessels of an inflamed eye, and when injected into the dorsal lymph sac of the frog it acts like a narcotic or cerebro-spinal poison.

As freed of the red substance the sulphate of the active principle behaves as follows: It is very soluble in water, fairly soluble in weak alcohol (50 per cent), almost insoluble in absolute alcohol, and quite insoluble in ether, acetone, ligroine and chloroform. Its aqueous solution, even when freed from adherent sulphuric acid, has a slightly acid reaction. The addition of iodine water to a neutral solution does not give a rose-red color. Alkalies added to a strong solution give a brown color which deepens on heating. Ferric chloride gives a purplish brown, almost black in concentrated solution, which ou the addition of tartaric acid and an alkali passes into a deep red color. Before the removal of the carmine-red substance the addition of ferric chloride gives the well-known emerald green color, which passes into red on the addition of an alkali.

It is evident that our sulphate gives V^ulpian's ferric chloride reaction, though somewhat changed by the removal of what we take to be the chromogenic substance which gave his iodine reaction. It also promptly reduces silver nitrate in alkaline solution, but does not reduce Fehling's solution even on boiling.

Probable Eelation to the Alkaloids.

More than a year ago, during our first studies with suprarenal extract, we were struck with the fact that every extract entirely free of proteids and physiologically active gave a fine pyrrol reaction when subjected to dry distillation. This is evidenced both by the odor and by the pine sliver reaction. A small quantity of the isolated sulphate also gives the pyrrol reaction when heated either alone or with zinc dust.

We attach considerable importance to this reaction. As is well known, alkaloids in general give pyrrol ou dry distillation ; morphine, for instance, on being heated with 10 parts of zinc dust gives off pyrrol, ammonia, trimethylamine, pyridine, phenanthrene, etc.* During the past winter we made


  • We are well aware that certain salts of glutaminic, pyromucic

and its related acids also yield pyrrol on dry distillation. These compouuds, however, like the proteids and their allies, appear to us to be excluded.


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several attempts to prove the presence of pyridine among the products of dry distillation of the active principle as above isolated, as its detection would prove that our principle was to be classed among the alkaloids.

In attempting to show the presence of pyridine we heated the active principle with zinc dust in a current of dry hydrogen and passed the distillation products through a test tube and two small flasks, the tube being placed in a cooling mixture, the first flask being partly filled with dilute sodium hydrate, and the second with dilute hydrochloric acid.

At the close of the experiment the test tube gave off alkaline vapors that smelled strongly of trimethylamine and had in addition a peculiar sweetish odor. The contents of the test tube diluted with water gave a jDrecipitate with bromine water and with copjier sulphate, but with the latter reagent the fine blue color characteristic of pyridine did not appear. The presence of amines seems to render difficult the detection of small quantities of pyridine. The contents of the third flask on exposure to the air took on a rose-red color and after a time threw out a precipitate of the same tint. Both flasks gave off the odor of benzaldehyde.

The following experiment was also made with a little of the sulphate, which no longer gave the rose-red reaction with iodine but which still contained a little of the coniine-like substance. For two hours it was kept at 150° C. in a sealed tube with 35 per cent, hydrochloric acid. On shaking out with ether a considerable crystalline residue was obtained which, without much purification, melted sharply at 130° C. and had all the properties of benzoic acid.

In the above decomposition experiments the quantity of material at command was small, perhaps not more than onefifth of a gramme at a time, and not entirely pure. We do not, therefore, lay much stress on our failure to detect pyridine.

The fact that the nitrogen of our compound is given off in the form of amines and pyrrol gives strong ground to believe that our substance is to be classed with the pyridine bases, using this term in a broad way. Its basic character, its ability to take up acid radicles, as illustrated by the formation of a benzoyl product, its reducing power and its color reaction with ferric chloride are all points which can be urged in support of this view. Furthermore, cupric acetate, the serviceableness of which as a precipitant of carbo-pyridine bases has been shown by Gautier and Landi,* also precipitates our active principle; and iodine chloride, which Dittmarf found to give brown or yellow halogen addition-derivatives with a large number of the alkaloids, gives with a neutral or slightly acid solution of our active sulphate a brownish flocculeut precipitate.

Of less weight in this connection, but nevertheless of some value, is the fact that its physiological action and its power in small doses is again in accord with what is known of alkaloids. Strychnine, thebaine and other alkaloids are readily called to mind as able to raise the blood pressure, and recently TunnicliffeJ has placed piperidine in the same list. The


•Compt. rend., cxiv (1892), 1154-1159.

fBerichte d. deutscb. chem. Gesellsch., xviii, 1612.

tCentralbl. f. Physiol., x, No. 25, 777.


pyrrol* bases are also physiologically active, although less attention has been paid to them.

Pyrocatechin cannot be split off from the Blood-Pressuke-Raising Constituent.

As already said, Miihlmann has stated with great positiveness that the blood-pressure-raising constituent is pyrocatechin joined to some other substance, probably an acid. Miihlmann does not offer sufficient proof for his conclusion ; and even had he proved the presence of pyrocatechiu in the gland itself, this is a very different thing from showing that it enters into the chemical constitution of the blood-pressureraising constituent.

We have repeated Miihlmann's work and have found that after boiling the medullary substance with hydrochloric acid, the ether takes up a trace of Vulpian's substance, as well as a substance that reduces Fehliug's solution.

The ether residue also gives a precipitate with neutral lead acetate which, on decomposition with dilute sulphuric acid, sets free a compound that gives with ferric chloride the reaction so characteristic of pyrocatechiu. Our blood-pressureraising constituent is not precipitated by lead acetate and could not, therefore, have been responsible for this result.

Furthermore, on decomposing a fairly large quantity of the crude benzoyl product before referred to and shaking out the resulting benzoic acid with ether, we have twice found that the ether has taken up in addition to the benzoic acid a small quantity of a substance which reduces Fehling's solution and gives a precipitate with neutral lead acetate. On decomposing the resulting lead compound with dilute sulphuric acid and neutralizing the filtrate, we obtained a solution which behaved with ferric chloride in the way characteristic of pyrocatechiu. The quantity of this lead compound obtained has been too small for analytical purposes.

We consider it, therefore, still uncertain whether or not a little pyrocatechiu is present in the gland.

That the blood-pressure-i-aising constituent is, however, not a pyrocatechiu derivative seems to us certain. To prove this we used, not the entire gland nor the medullary substance, but the active principle itself, as isolated by us by decomposing the benzoyl compound.

We have used large quantities of material representing in each experiment the active principle of several thousand glands. We have boiled this with hydrochloric acid of varying strength and for varying lengths of time, and in no case have we been able to find in the ether used as a solvent any trace of a substance that would reduce Fehling's solution or give a precipitate with lead acetate. Inasmuch as some of the chromogenic substance always passes into the ether from acid solutions, these two reactions are both necessary to establish the presence of pyrocatechin. In other words, we have failed to split off pyrocatechin from the active principle as isolated by us. If present, it could hardly have eluded our search, for even a minute quantity may be made to give a precipitate with neutral lead acetate.


  • Jac. Ginzberg, Ueber das Verhalten des Pyrrols, etc., luaug.

Diss., Konigsberg, 1890.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 76.


We propose during the coming autumn to continue this work. Having made arrangements for the use of a large amount of material, we hope to secure both the benzoate and the sulphate in a form pure enough for analysis and for further chemical study.

(Summary.

We may sunnnarize the results of our work as follows :

The blood-pressure-raising constituent of the suprarenal capsule may be completely precipitated fi-om an aqueous extract by treatment with benzoyl chlorideand sodium hydrate, according to the Schotten-Baumann method.

On decomposing the resulting benzoyl products, a residue is obtained which possesses great physiological activity. It gives the color reactions of Vulpian, reduces silver nitrate and possesses the other specific qualities of suprarenal extracts.

AVith the help of alkalies a carmine-red pigment may also be separated from these decomposition products. We take this pigment to be that one of the chromogenic substances of Vulpian which gives the rose-carmine color when suprarenal extracts are treated with oxidizing agents or alkalies.

A volatile, basic substance of a coniiue-like odor is always found to accompany the crude benzoate. When these substances ai'e removed the active principle is left as a highly active sulphate or hydrochlorate, as the case may be. It is therefore a basic substance. Its salts give a color reaction with ferric chloride; they also reduce silver nitrate, but not Fehling's solution.

It is not j)ossible to split oft' pyj'ocatechin from this isolated active principle. The fact that dry distillation causes the appearance of amines and pyrrol in abundance, taken in connection with its ability to take up acid radicles, its reducing power, its precipitability by cupric acetate and iodine chloride, and its jihysiological action, lead us to conclude that our active principle is to be classed with the pyridine bases or alkaloids.

Addendum, June 15, 1897.

Since the foregoing paper was read before the Association of American Physicians on May 6, 1897, B. Moore has published a paper in the Jotcrnal of Physiology, vol. xxi, Nos. 4 and 5, May 12, 1897, entitled, "On the Chromogen and on the active Physiological Substance of the Suprarenal Gland." In this paper it is suggested that the active principle may be a pyridine derivative. Moore's conjecture is based, lirst, on a formula calculated by him from a combustion analysis of Krukenberg, made with an impure, hygroscopic, noncrystalline residue obtained by merely decomposing and drying a precipitate secured out of an alcoholic extract of the gland with the help of basic lead acetate. The calculated formula, the carbon content of which differs by 1.33 per cent, from that actually found by Krukenberg, is CsHuNO.!, and Moore points out that in it the ratio in which the elements carbon and nitrogen stand to each other is the same as in pyridine, CrHr.N. Now such a calculation, though suggestive to the investigator, furnishes no proof of the presence of pyridine, for Krukenberg could not possibly have had in hand a chemical individual uncontaminated with other constituents of the gland. Krukenberg himself admits that his


material was a mixture of unaltered pigment and its decomposition products. It is also certain that it was contaminated with other constituents of the gland. This is proved by the fact that basic lead acetate precipitates several of the constituents of the gland which pass into alcohol, and also by the fact that the analysed material contained 0.0(38 per cent, of sulphur and from 1.18 per cent, to 1.44 per cent, of ash.

A second reason given by Moore in supj)ort of his conjecture is that when "some suprarenal extract was cautiously fused with caustic potash so as to avoid charring, the peculiar odor of pyridine was at ouce obtained." He admits that proteids were present in this extract, and that jjyridine and its homologues arc formed in the destructive distillation of proteids, but states that the experiment was "conducted so as to avoid charring," and considers this a sufficient safeguard. This experiment has also no value, for the odor of pyridine can always be obtained when a mixture of dry, powdered proteid and powdered caustic potash are fused together so as to avoid charring. This experiment, therefore, must be made with material entirely free of proteids. Since reading Moore's paper we have fused a little of our active i)rinciple with caustic potash, but have failed to detect pyridine. If present in the molecule of the active principle, it is evident that larger quantities of the material must be used to prove it. Only indisputable chemical proofs can establish the presence of Jiyridine ; the odor is not enough. We have frequently in various manipulations with the active substance met with what we took to be the odor of pyridine, but on shaking out with ether and adding an ethereal solution of hydrochloric acid and evaporating the ether we have been unable to detect pyridine in the residue.

Description of the Tracings.

Fig. 1. Tracing. Dog aniesthetized with morj)hine ; curare and artilicial respiration, both vagi cut. Injection of the active sulphate, freed from the carmiuesubstanceaud coniinelike body, at X.

A =: running base line.

i?z::time record.

(7 z= curve of the blood pressure, canula in the right carotid artery.

Fig. 3. Tracing. C!onditions of the experiment as in Fig. I. Injection at X of a highly active sulphate which still gives the rose-carmine color with iodine water and still contains some of the coniine-like substance which does not raise the blood pressure. The blood pressure is so high that the mercury is driven out of the manometer.

Fig. 3. Tracing. Conditions as in 1. Injection at X of a material which is still highly active although it had been boiled with 5 per cent, sodium hydrate for one hour. In this experiment a number of injections had already been made; the pressure had fallen to the normal before the injection indicated at X was made.

DESCRIPTION OF THE JOHNS HOPKINS HOSPITAL

IJy JOHN S. lili, LINOS, M. I)., LL. D.

Ctmtalnlng 56 largo quarto plates, phototypes, and lithographs, wlih views, plaiiH iiutl ilotatl drawlugaof all the butldlugs.aiul their Interior arraugemeuts— also wood-cula of apparatus aud Uxtures; also 116 pages of letter-press describing the plans followed lu thecoustruollou, and giving full details of heatlug-apparatut, veutUatlou, sewerage aud plumblug. Price, bound lu cloth, $7.oO.



NOTES ON NEW BOOKS.

Anomalies and Curiosities of Medicine, being an encyclopedic collection of rare and extraordinary cases, and of the most striking instances of abnormality in all branches of Medicine and Surgery, derived from an exhaustive research of medical literature from its origin to the present day, abstracted, classi fled and indexed. By Georqe M. Gould, A. M., M. D.,and Walter L. Pyi.e, A. M., M. D. With 295 illustrations and 12 half-tone and colored plate.s. 908 pp. (Philadelphia : W. B. Saunders, 1897.)

Tliestatementof Gibbon that objects which are only singular without being pleasing may excite surprise but soon lead to satiety and <iisgust, does not apply to this volume, which is thoroughly interesting from beginning to end. The attempt of the authors "to briefly epitomize and to arrange in order the records of the most curious, bizarre and abnormal cases thatare found in medical literature of all ages and all languages," has been most successful. The book is thoroughly scientiflc in its treatment of the varied material which has been gathered with an industry which calls forth admiration. The Urst six chapters will probably be read most generally and relate to anomalies of conception, birth and development, and are of special interest to the gynecologist, obstetrician and student of legal medicine. Chapter seven relates to gigantism, dwarflshness, obesity and abnormal leanness, and the accompanying illustrations form a curious collection of anomalies suggestive of a dime museum.

The chapter on longevity taxes one's faith rather more than any other. Think of Henry Jenkins dying at the age of 169 years ; Thomas Parr at 152 ; Jean Korinat 172 and his wife atl64, and ason left an orphan by their untimely death at the tender age of 116 ; Petretsh Zartan at 185 or 187 (authorities differing), who walked a mile to the post ofiice a few days before his death to ask for alms ; and many other well-authenticated instances of nearly equal age.

The chapter on anomalous mental and nervous diseases is so complete it is a matter of surprise that it does not include the history of the young man in Ohio who became totally blind at the age of seven months, and who, while receiving an education at the school for the blind, in consequence of a fall, lost both hearing and speech. After a time, his eyesight being restored by the fall, he was transferred to an establishment for the education of deaf mutes. Here eventually his hearing was suddenly restored, but epileptic attacks developed which required hospital treatment, this time in an institution for the insane. This well-authenticated tale was published in considerable detail in one of the State repoits and deserves a place in these annals. The chapter on Historic Epidemics is timely, especially the full account of the bubonic plagues of the middle ages.

An excellent feature of the book is the judicial spirit shown by the authors. Facts are weighed and reasons are advanced for the conclusions which are reached. The book is well printed and finely illustrated and is worthy of a large success. Every chapter is of interest to every physician.

Text-Book of Materia Medica, Therapeutics and Pharmacology. By G. F. Butler, M. D. [Philadelphia: W. B. Saundem, 1896.)

This work is dedicated to the " Medical Students of the United States," and we have no doubt that many of them who enjoy buying the latest work on this branch of medicine will find it serviceable. It cannot be said to replace the oliier works of Wood, Hare and others. There is very little true original thought in it, which should be the the real reason for the publication of any new book, especially to-day, when there is altogether too much production of simply transient works. As the author states in the preface : " From the U. S. Pharmacopeia chiefly, and from the National Dispensatory, have been adopted almost verbatim, the ' origin ' and 'description and properties' of tlie various drugs under consideration," so it is more in his arrangement of his material that we must


look for originality. He classifies the drugs by their properties, rather than alphabetically, as is done by Hare. Both methodshave their advocates, and [lersonally, as it is much the most rapid way to look up any given drug, we prefer the latter method. Butler still further cljftsifies the drugs into so called " Disease-Medicines," a very unscientific term, as he himself recognizes, and "SymptomMedicines." In such a classification no two persons willagree as to the class to which certain medicines will belong most properly, and thus it becomes confusing and time-consuming to search for the drug wanted. The author says: "A genuine specific is tolerated only by the system in which it antagonizes some disease. For instance, A and B are put under a prolonged course of mercury ; A is salivated beyond recognition, while B's health improves — simply for the re.ison that B had syphilis, which A had not." Such general remarks are often not true, and the example given is a very poor one, for we all know that syphilitic patients may be salivated, and sometimes as severely as those who are not syphilitic. Also many ]>atients who have not sypliilis may take mercury in large doses for long periods of time without becoming salivated. We do not understand the following sentence: "Quinine was formerly considered a specific in malaria, until the fact was recognized that the drug is analogous to a normal constituent of healthy bile in its action upon plasmodia malariae." W^e believe that by most authorities quinine is still considered to be a specific in malaria, whatever the action of bile may be. In a work which covers so much ground as this text-book, the value depends on an equal balancing of the different parts, and especially, in the description of the drugs, of careful omission of all unnecessary parts, and still more exact and concise information on all important points. Each author naturally finds special interest in certain parts of his work, and so not knowing these it is hard to criticise the book justly. But in the 650 pages given to drugs and their actions we feel that much improvement could have been made with careful revision — some parts omitted, and other information of more importance added. We think it quite out of place to introduce in such a work declensions of simple Latin words and other rules of Latin grammar, which should be known by every student before he begins the studj- of medicine, and if he does not know them, he should not be helped to the knowledge in this superficial manner.

Diseases of the Ear, Nose and Throat. By S. P. Bishop, M. D. (Philadelphia : F. A. Davis Co., 1897.)

This book, we think, fulfills pretty satisfactorily the object of the author, as expressed in the preface; he says: "This work was designed, first to help students in preparing for their degree ; second, for those progressive practitioners who wish to acquire the proficiency necessary to properly treat those patients who are unable to visit specialists ; and third, for those who are gradually exchanging their general practice for special work in these branches." The chapter on blood-serum therapy in diphtheria seems out of place ; it is merely an abstract of a few of the articles which liave appeared on this subject during the past two years, and we see no good reason for introducing it here. The work on the whole is a fair presentation of our knowledge in these diseases, without any attempt to take up any of them at length. The treatment as given is generally satisfactory and simple. We do not agree with the author in considering hay-fever, or "nervous catarrh," as he prefers to call it, a result of uric acid diathesis. There are many questions in the study of this disease which are as yet quite inexl)licable, and this theory of its causation is insufficient to explain them all ; the neurotic character of the disease is well established, and that uric acid may in some caees play an inijiortant role in this nervous affection is undoubted, but it is also equally certain that other important causes play their role too in determining this malady.

This book is clieaply gotten up and the cuts are of poor quality ; tlie colored illustrations also seem very unsatisfactory. Many of


July, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


159


the cuts are reproductions of instruments wliich by this time should be l^nown to all practitioners and to every student graduating from a medical college. These simply add to the expense of the book without adding to its intrinsic value.

Essentials of Physical Diagnosis of the Thorax. Second Edition.

By Arthur M. Cokwin, M. D. (Philadelphia: W. B. Saunders,

189a.)

That there is a demand for such a quiz-compend or aid in cramming for an examination is shown by the fact that a second edition of this small book has been called for. We cannot recommend it, however, for like other similar works it fails in attempting to condense much knowledge in a very limited space and although tolerably well arranged, there are numerous statements of fact with which we cannot agree. The varieties of tympany (p. 69) are confusing and not generally used and were better omitted in such a work. In the discussion of heart murmurs there is much needless repetition, and on p. 176 the mitral systolic murmur described as occurring in aortic insufficiency, otherwise known as Flint's murmur, is presystolic in time. The chapter on congenital lesions of the heart is treated too briefly to be of service, as is also the one on hydatid cyst of the lung, which, when jiriniary, is not a condition easy to diagnose, nor could the signs of it as given by the author differentiate it from pleurisy. 8pasm of the columnar carnese is a condition which may occur, but it is hardly one of which a diagnosis could be made. Acute endocarditis without valvular lesion is not a condition which can be recognized clinically, and inorganic aortic systolic murmurs should usually be doubted. The ratio of the inspiratory sound to the expiratory is not as tiiree to one, nor in asthma is the dyspnosa (orthopncea) chiefly expiratory. CheyneStokes respiration does not ordinarily accompany opium poisoning. No worse instrument for clinical instruction could well be devised than the multiplex stethoscope, of which there is an illustration in the beginning of this work.

Pathological Report of the Illinois Eastern Hospital tor the I (Chicago: Blakely rrinting Co., 1896.)

This is an excellent report, full of much valuable mateiial, and Dr. Adolf Meyer deserves much credit for it, considering the difficulties under which the work was prosecuted, due to a lack of general facilities for carrying it on. We cannot criticise any shortcomings when we read his closing remarks. He says: "It may justly be said that the publication of so much raw material is of little use. To polish the report, away from the records and the material, did not seem to he in the interest of the accuracy of a picture of the working of the laboratory which had barely come into existence at the end of the period covered. The work was planned on a broader basis than it was feasible to carry out in the short period. The idea was that the plan of publishing ' interesting' cases only was not in the interest of sober study of the daily experience, that selecting cases might lead to illustration of preconceived ideas instead of the facts as they present themselves in reality, and that at the present stage of psychiatry a consideration of all the things seen wouM be less dangerous than arbitrary selection. The same jirinciple should be carried out in the clinical side as well." Although much of the material is raw, yet many facts of interest are to be found — perhaps the most interesting being that 32 per cent, out of 49 cases of terminal dementia, and 27 per cent, of 192 cases of mental diseases, including the first series, died of florid tuberculosis. Of course without fuller statistics as to the class of patients in the hospital, too much stress should not be laidon these figures, but nevertheless the percentage is high. A case of acute mania, dying presumably of sulphonal poisoning, shows the necessity of the utmost care being used in the administration of drug.ito patients with mental diseases to avoid accidents of this sort. We shall await with pleasure sui cessive reports from Dr. Meyer, who has now transferred his work to the Worcester State Hospital and


nsane.


Clark University, and trust he will be able to describe some of the finer microscopical findings in brain and cord lesions from the interesting material at his disposal.

St. Thomas's Hospital Reports. New Series. Vol. XXIV. i London,

1895.)

The first half only of this volume is taken up with detailed papers, and the second half with statistics of the different departments of the hospital, and brief abstracts of cases, medical and surgical. Among the papers here preseuted, two are worthy of special note. The article on " Osteo-arthropathy and its Relationships," with report of a case of pulmonary hypertrophic osteoarthropathy, both by Dr. Walters, is a very valuable contribution to our knowledge of this curious condition and its relationship to akromegaly. It is an exhaustive study, with a brief abstract of all the cases reported of this bone disease up to the time of the publication of this volume. The other paper is on "Enteric Fever and Sewage Gas," in which 11 cases of typhoid fever are described as resulting from poisoning with sewer gas in one hospital within a short space of time. Here milk, water and food as possible sources of the contagion could apparently be eliminated without doubt, and the only other discoverable source was a water-closet into which typhoid organisms had probably been discharged but a few weeks before the outbreak of this small epidemic, which ceased as soon as the sewage pipes were overhauled and modified. With the modern belief that typhoid fever in nearly every case re>ult8 from milk, water or food contaminated by the typhoid organism, this epidemic raises the most interesting question as to whether or not typhoid bacilli may enter the body through the lungs and thus cause the fever. There are other articles on tuberculous disease in the knee-joint, and relapse in the si)ecific fevers, which will repay careful reading.

Feeding in Early Infancy. By Arthur V. Meigs, 51. D. (Vhiladelphia: W. B. Saunders, 1896.)

In this paper Dr. Meigs emphasizes the results of his milk analyses as expressed in his earlier publication, and describes in detail the preparation of his food, based on these results.

He finds that human milk never contains more than one percent, casein, cow's milk three times this amount, other constituents being present in about equal quantities. In his preparation cow's milk is therefore diluted with lime water, and cream and sugar added in definite proportions. The food, piepared after this manner, has been used for a number of years by the author, with satisfactory results.

He thinks thatsulijecting milktohightemperaturesdetracts from its usefulness as an infant food ; therefore it is better to be assured of its source and avoid sterilization.

This course seems hardly practicable, and the injurious effect accredited to sterilization is not sustained by most writers on the subject.

Proceedings of the American Medico-Psychological Af-sociation at the 52d Annual Meeting, held in Boston, May 26-29, 1896. {American Medico-Psychological Associaiion, 1896.)

The proceedings of this society occupy nearly 300 large papers, pretty closely printed ; but all the papers are good, while some are of especial value. There is an interesting address on psychological education by Stanley Hall, a leading authority on such a subject; and there are important contributions by Brush, Worcester, Hoch, and Berkley. The paper by Hoch, on " General Paralysis in Two Sisters," is perhaps, while one of the most thorough articles, the one of most general interest. To students who have given much time to the study of the blood, the paper on " Leucocytosis Associated with Convulsions," by Burrows, will open up a point of much interest as to the cause of leucocytosis, whether or not it be due to a form of auto-intoxication.


160


JOHNS HOPKINS HOSPITAL BULLETIN.


[So, 76.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 i>ages, 99 plates.

Report in Pntliologry.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berkley, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

Mall, M. D.

Report in Dermntologry. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. D., and Emmf.t Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the BO-called

Parasites found in Various Lesions of the Skin, etc.; Two Cases of MoUuscuni

Fibrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duhring). By

T. C. Gilchrist, M. D.

Report In Patholog^y. An Experimental Study of tin' Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Meillcine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Post-febrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry Toulmin. M. D. Rare Forms of Cardiac Thrombi. By WtLLiAM Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in Medicine. Tubercular Peritonitis. By William Osler, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler. M. D.

Report in Gynecology. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D.. and Hunter Robh, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gynecological Cases. By Howasd

A. Kelly, M. D., and Albert A. Ghrisket, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of Checking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoma of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of the Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snri;:ery, I. The Treatment of Wounds with Especial Reference to the VaUu^ of the Blond Clol

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in tVenrologT-, I. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. .\cute Angio-Ncurotic Oedema. By Charles E. Simon, M. D. Haematomyelia. By August Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henry M. Thomas, M. D.

Report in Patbolo^y, I. Amoebic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleur, M. D.


Volume III. 706 pages, with 69 plates and figures.

Report in Patholosry*

Papillomatous Tumors of the Ovary. By J. Whitridge Williams, M. D.

Tuberculosis of the Female Generative Organs. By J. Whitridge Williams, M. D. Report in Piitliologry*

Multiple Lympho-Sarcomata, with a report of Two Cases. By SiMON Flexner, M. D.

The Cerebellar Cortex of the Dog. By Hknry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology,

The Gynecological Operating Room; An External Direct Method of Measuring the Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Enterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Sourrc of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexed Uterus. By Howard A. KiXLY, M. D.

Potassium Permanganate and Oxalic Acid as Germicides against the Pyogenic Cocci. By Mary Sherwood, M. D.

Intestinal Worms as a Complication in Abdominal Surgery. Bj A. L. Stavklt, M, D.


Gynecological Operations not involving Coeliotomy. By Howard A. Kelly, M. D. Tabulated by A. L. Stavely, M. D.

The Employment of an Artificial Retroposition of the Uterus in covering Extensive Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D.

Photography applied to Surgery. By A. S. Murray.

Traumatic Atresia of the Vagina with Hsematokolpos and Hxmatometra. By Howard A. Kelly, M. D.

Urinalysis in Gynecology. By W. W. Russell, M. D.

The Importance of employing Anaesthesia in the Diagnosis of Intra-Pelvic Gynecological Conditions. By Hunter Robb, M. D.

Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D.

<)ne Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age. By Howard A. Kelly, M. D., and Mary Sherwood, M. D.

Abdominal Operations performed in the Gynecological Department, from March 5, 1890, to December 17, 1892. By Howard A. Kelly, M. D.

Record of Deaths occurring in the Gynecological Department from June 6, 1890, to May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler. M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Neurology.

Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of "the Submaxillary Gland of Mu^ miisruln.^; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley. M. D.

Report in Surgery. Tlie Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1894. By W. S. IIalstkd, M. D.

Report in Gynecolof^y. Hydn)salpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Ctllen, M. B. Report in Patlioloe^y. Deciduoma Malignum. By J. Whitridge Williams, M. D.


\\)LUME V. 480 pageSj with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typlioid Fever. By William Osler, M. D., with additional papers by G. Blumer, M. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, M. D.


Volume VI. About 500 pages, many illustrations.

Report in Nenrolojsry.

studies on the Lesions produced by the Action of Certain Poisons on the Cortical Nerve Cell (Studies Nos. I to V). By Henry J. Berkley, M. D.

Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I.— Alcohol Poisoning.— Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (Ethyl Alcohol); P»rt II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Serum on the Cortical Nerve Cell; Part III.— Ricin Poisoning.— Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by Chronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia.— Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V. — Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from the Effects of Alcohol and Ricin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic BulKir Paralysis. By Henry J. Berkley, M. D.

Report in Pntliologry.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. Bv Thomas S.

<'l-LLEN. M. B.

fii^aiancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

Ovum and Spermatozoa. By Thomas S. Cullen. M. B., and G. L. Wilkins. M. D. Adciio-Myoma Uteri Diffusum Benignum. By Thomas S. Cttllen, M. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infanta. By

William D. Booker, M. D. The Pathology of Toxalburain Intoxications. By Simon Flexner, M. D. The price of a set houiid in cloth [VoU. I-Vl] of the Hospital Reports m

$30.00. Vols. If II and III are not sold seimrateltj. The price o/

Vols. 11% r and ri is $5.00 each.


MONOGRAPHS ON DERMATOLOGY, MALARIAL FEVERS AND TYPHOID FEVER. The following papers are reprinted from Vols. I, IV and V of the Reports, for those who desire to purchase in this form: STUDIES IN DERMATOLOGY. By T. C. Gilchrist, M. D., and Emmkt Rixford,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, bound in paper,

$3.00. THE MALARIAL FEVERS OF BALTIMORE. By W. S, Thayer, M. D., and J.

Hewetson, M. D. And A STUDY OF SOME FATAL CASES OF MALARIA.

By Lewellvs F. Barker, M. B. 1 volume of 280 pages. Price, in paper, f3.75. STUDIES IN TYPHOID FEVER. Bv William Osler. M. D., and othere. Extracted

from Vols. IV and V of the Johns Hopkins Hospital Reports. 1 volume of 481

pages. Price, bound in paper, $3.00. Subscriptions for the above publications may be sent to

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The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by THE FRIEDENWALD CO., Baltimwr, Single copies nuiy he pronired from Messrs. GUSHING & CO. and the BALTIMORE NEWS COMPANY, Baltimore. Subscriptions, $1.00 a tityir, may tte addressed to the publishers, THE JOHNS HOPKINS PRESS, BALTIMORE; sini/lv topics will be sent by mail for fifteen cents each.


BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. Vm.-Nos. 77-78.]


BALTIMORE, AUGUST-SEPTEMBER, 1897.


[Price, 15 Cents.


GOnSTTEJaSTTS.


PAGE.

Influence of Louis on American Medicine. By Willia.m O.SLEB, M. D., - - - 161

AVilliam Harvey as an Embryologist. By William K. Brooks, LL. D., - - - - - - 167

Long, the Discoverer of Anaesthesia. A Presentation of lii.s Original Documents. By Hugh H. Young, A. M., M. D., - 174

The Early History of Ophthalmology and Otology in Baltimore (1800-1850). By Harry Friedknwald, A. B , M. D., - 184


Joseph Friederich Piringer: His Methods and Investigations.

By Harry Friedenwald, A.B., M. D., 191

Proceedings of Societies :

Hospital Medical Society, " - 195

Hsematomyelia from Gunshot Wound of the Cervical Spine [Dr. Gushing].

Notes on New Books, _ . - _ 197

Books Received, 197


INFLUENCE OF LOUIS ON AMERICAN MEDICINE.

By William Oslek, M. D.


Harvey and Sydenham, types of the scientific and the practical physician, though contemporaries, were uninfluenced, 80 far as we know, by the other's work or method. Harvey had little reputation us a practical physician, and Sydenham cared little for theories or e.\periment. Modern scientific medicine, in which these two great types meet, liad its rise in France in the early days of this century. True, there had lived and worked in England the greatest anatomist and medical thinker of modern times; but John Hunter, to whose broad vision disease was but one of the processes of nature to be studied, was as a voice crying in the wilderness to the speculative, theoretical physicians of his day.

Bichat's Anatomie Gaicrale laid the foundation of the positive or modern method of the study of medicine, in which theory and reasoning were replaced by observation and analysis. Laennec, with the stethoscope, and with an accurate study of disease at the bedside and in the post-mortem room, almost created clinical medicine as we know it to-day.

The study of fevers occupied the attention of all the great physicians of the time. Fever — what it was, how it should be treated. What a vast literature exists between Sydenham and BroussaisI What a desolate sea of theory and speculation !


•Read before the Stille Society of the Medical Department of the University of Pennsylvania.


No one had been more influenced by Bichat's brilliant teachings than Broussais, who ruled supreme in the medical world of Paris in the early decades of this century. A strong believer in careful observations at the bedside and in the jiostniortem room, he was led into hoj)eless error in attributing fevers and many other disorders to irritation in the stomach and intestines — his gastro-enteritis.

Writing in the American Medical Recorder, July, 1831, an American student, Dr. F. J. Didier, says of the Paris professors of that date, "They were always talking of Hippocrates, Galen, Oelsns, etc., as if not a particle had been added to the stock of knowledge since their time." And again, " The doctrines of John Brown, mixed up with the reninantsof humoral pathology, form the basis of the present system."

The same mi.xture prevailed early in the fourth decade, as you may see from Broussais' Pathology, the American edition of which was issued in 1833, and from Jackson's (Samuel) Principles of Medicine, published in the same year.

Upon this scene, when Broussais was at the height of his fame, came Louis. He, with his friends Andral and Chomel, were very important factors in substituting finally in the study of medicine, for speculation and theory, observation and method.

The chief facts in Louis' life may be thus briefly stated. He was born in 1787 at Ai. He began the study of law, but abandoned it for that of medicine. He seems not to have


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beeu of a very strong constitution, as he did not pass the inspection for military service. He began the study of medicine at Eheinis, and completed his course in Paris, where he graduated in 1813, in the twenty-seventh year of his age. While waiting at home, hesitating what he should do, M. le conite de Saint-Priest, who occupied au official position in Russia, hajipened to stay for a few hours in the town of Ai to see Louis' family, and it was suggested that the young physician should accompany him to Russia. He consented and in St. Petersburg obtained a diploma to practice. For three years he seems to have had no settled abode, but wandered about with his friend, who was Governor of one of the provinces. He then settled in Odessa, where he remained for four years and practiced with great success. In the last year of his stay in Odessa he was very much disturbed by the high rate of mortality in children with diphtheria, and this appears to have determined him to abandon for a time the practice of medicine and to devote himself to study. With this object in view he returned to Paris and for six months attended the practice at the Children's Hospital. Among the younger physicians in Paris he found an old fellow-pupil, Chomel, physician to La Oharite, who offered him opportunities for work in his wards. Louis at this time was thirty-four years of age. Here for six years uninterruptedly he set himself to work to study disease in the wards and in the post-mortem i"oom. At first he appears to have occupied the position simply as a voluntary assistant and friend of Chomel, but subsequently he became his chef-de-cliniqiie, and during this period he occupied a room in the entresol of the hospital. He was a voluminous note-taker and collected in this time au enormous number of important facts.

This remarkable feature in Louis' life has scarcely been dwelt upon sufficiently. I know of no other parallel instance in the history of medicine. It is worth while reading the brief extract from Dr. Cowan's introduction to his translation of the work on Phthisis. " He entered the hospital of La Oharite as a clinical clerk, under his friend. Professor Chomel. For nearly seven years, including the flower of his bodily and mental powers (from the age of thirty-three to forty), he consecrated the whole of his time and talents to rigorous, impartial observation. All private practice was relimiuished, and he allowed no considerations of personal emolument to interfere with the resolution he had formed. For some time his extreme minuteness of inquiry and accuracy of description wei'e the subjects of sneering and ridicule, and cui bonof was not infrequently and tauntingly asked. The absence of any immediate result seemed for a time to justify their contempt of a method involving too much labor and personal sacrifice to be generally popular or easily imitated ; and M. Louis himself, at moments, almost yielded to the increasing difficulties of the task he had undertaken. No sooner, however, were his facts sufficiently numerous to admit of numerical analysis than all doubt and hesitation were dissi2}ated, and the conviction that the path he was pursuing could alone conduct him to the discovery of truth became the animating motive for future perseverance. Many of the results to which he arrived soon attracted general attention, and among those who had formerly derided his method while they admired his zeal, he found many toapplaud


and a few to imitate. From this moment may be dated the presence of that strong impression of the necessity of exact observation by which the school of Paris has beeu since so distinguished, and which is now gradually pervading the medical institutions of the continent and our own country; it is undoubtedly to the author of the present volume that we ought to ascribe the practical revival of that system, which had for ages been verbally recognized but never before rigorously exemplified."

The following works appeared as a direct result of his studies during these six years:*

" In 1823, a memoir on perforation of the small intestines, in acute diseases; a second, on croup in the adult; a third, on the communications between the right and left cavities of the heart (Archives de medecine).

" In 1824, two memoirs on the pathological anatomy of the mucous membrane of the stomach ; another on pericarditis.

"In 1826, a memoir on abscess of the liver; another on the condition of the spinal marrow in Pott's disease; a third on sudden and unforeseen deaths; a fourth upon slow but anticipated deaths, but which anatomy will not explain; a fifth on the treatment of tajuia by the Darbon potion (Archives de medecine).

"In 1825, his Anatomical Researches, etc., on Phthisis (1 vol. 8vo) ; reprinted with many additions in 1843.

" In 1828, Researches on the Typhoid Affection or Fever (2 vols. 8vo); reprinted with many additions in 1841."

Louis introduced what is known as the Numerical Jlethod, a plan which we use every day, though the phrase is not now very often on our lips. The guiding motto of his life was "Ars medica tota in observation ibus," in carefully observing facts, carefully collating them, carefully analyzing them. To get an accurate knowledge of any disease it is necessary to study a large series of cases and to go into all the particulars — the conditions under which it is met, the subjects specially liable, the various symptoms, the pathological changes, the effects of drugs. This method, so simple, so self-evident, we owe largely to Louis, in whose hands it proved an invaluable instrument of research. He remarks in one place that the edifice of medicine reposes entirely upon facts, and that truth cannot be elicited but from those which have been well and completely observed.

American medicine felt the influence of Louis through two channels, his books and his pupils. Let us speak first of the former. No French writer of the century has had such a large audience in this country; all of his important works were translated and widely read. The work on phthisis, the first important outcome of five years' hard work at La Oharite in Ohomel's wards, was published in 1825. Much had already been done by physicians of the French school on this subject. Bayle's important Recherchcs had been issued in 1810, and Laennec had revolutionized the study of phthisis by the publication of his treatise on auscultation. I cannot enter into any detailed analysis of the work, but it is one which I can commend to your notice as still of great value, particularly as


  • Brief Memories of Louis and some of his Contemporaries. H.

I. Bowditch, Boston, 1872.


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a model of careful observation. The work was based ujjou the study of 133 cases observed in Chomel's clinic. The lesions observed at autopsy are first described under the different organs, with great accuracy and detail, and then summarized, following which is an elaborate description of the symjitomatology. I do not know of any single work on pulmonary tuberculosis which can be studied with greater profit to-day by the young physician. The fifty years which have elapsed, since its publication, and the changes which have taken place in our ideas of tuberculosis, diminish naught from the value of his careful anatomical and clinical presentation of the subject.

In 1829 appeared his second great work, Anatomical, Pathological and Therapeutical Researches upon the disease knoivn under the name of yctstro-enterite, putrid, adynamic, ataxic, typhoid fever, etc., com^mred with the most common acute diseases. It was based upon 138 observations made between 1822 and 1837. He analyzed and determined the lesions found in fifty patients who had died of the typhus fever, and compared these with alterations found in other acute diseases. Altogether for this work he states that he analyzed the changes in the viscera of 133 subjects and the symptoms of nearly 900. In his introduction to this work he quotes a sentence from Rousseau which is always to be kept in mind : " I know that truth lies in the facts, and not in the mind that judges of them, and that the less I introduce what is merely my own into the deductions I make from them, the more certain I shall be of approaching the truth." This work was translated by Dr. H. I. Bowditch in 1836. At the time of Louis' observations, although differences were recognized between the various forms of continued fevers, the profession had no accurate knowledge of the subject. It so happened that at this period the disease prevailing at Paris known as tyjihus was almost entirely what we now call typhoid fever, so that the anatomical lesions found by Louis in his fifty autopsies were chiefly in the intestines ; in all the Peyer's glands were diseased. His method was to analyze carefully the appearances found in the different organs in the series of fever cases, and compare them with patients who had died of other acute diseases; thus of course the contrast was striking in the very matter of involvement of Peyer's glands, which were more or less seriously changed in structure in all of the patients with the fever, while in the persons dead of other acute diseases the elliptical patches had no special redness or softening.

The symptomatology was also given in great detail, and the same painstaking comparisons were instituted between the subjects of the typhoid affection and those of other acute diseases. Louis' work convinced a majority of the members of the Paris school that the essential lesions in continued fevers were in the intestines, and Louis himself apjiears not to have had any idea whatever that the disease which he was studying was in any way different from the disease jirevailing in other parts of Europe and which we now know as tyjjlius fever.

The next important memoir, the essay on Blood-letting, had a very potent influence on professional opinion in this country. It appeared in Paris in 1835 and was translated by G. C. Putnam, with an introduction and appendix by Dr. James Jackson. As this learned physician remarks in his


preface, " If anything may be regarded as settled in the treatment of disease, it is that blood-letting is useful in the class of diseases called inflammatory, and especially in inflammations of the thoracic viscera." When one i-eads the reports of the treatment by bleeding up to about the year 1840, one is almost forced to ask the question, are the diseases the same ? or surely the patients must have possessed much more powerful constitutions than those which we are called upon to treat at the end of the century.

At the time of Louis' return to Paris, under the influence of Broussais' doctrine of irritation, local and general bloodletting was practised more extensively than at any previous period in the history of medicine. As an interesting illustration it may be mentioned that the trade in France and Spain in leeches had developed to proportions which assumed really those of a national industry, and even in this country I believe one of the medical societies offered a prize for the best demonstration of the practical method of cultivating leeches for medicinal purposes.

It must have been a terrible shock to Broussais and his adherents when Louis attacked the subject of blood-letting in pneumonia with his numerical method. For this purpose he analyzed 78 cases, 28 of which proved fatal, and in a second series 39 cases with 4 deaths. Among his conclusions were that pneumonitis is never arrested at once by blood-letting, and that the supposed haj)py effect on the progress of the disease was very much less than was commonly believed. Incidentally he remarks with reference to the practice of blistering which was in vogue at the time, that he had rejected the practice .after the treatment of 140 cases of pleurisy without losing a case. I would refer you particularly to Putnam's translation of this article, which you can obtain in any of the libraries, not only for Louis' work, but for the excellent introduction by Dr. Jackson on the value of the numerical method in medicine, and also for the appendices, analyzing the pneumonia cases of the Massachusetts General Hospital from 1834 to 1834 (inclusive).

To American students one of Louis' most valuable works is his Research on the Yellow Fever in 1828. On the 1st of November, 1838, Louis, with Ghervin and Trousseau, left for Gibraltar, where the disease prevailed. They made a very careful study of the symptoms and morbid anatomy, and on their return to Paris made a report to the Academy of Medicine, but the work remained in manuscript until Dr. Geo. C. Shattuck translated it into English and it was published by the Massachusetts Medical Society as Vol. X of their Library of Practical Medicine. The work did not ajjpear in French until 1844. It is chiefly valuable as a very accurate and careful record of a series of cases studied clinically and anatomically.

Powerful as was the effect of Louis' writings on American medicine, it cannot compare with the influence which he exerted through his pupils, who " caught his clear accents, learned his great language, made him their model." Of the great triumvirate of the French school of the fourth decade, Louis possessed a singular power of attracting hard-working, capable men, and this in spite of the fact that his rivals and friends, Chomel and Audral, possessed more brilliant gifts of


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a certain kind. As a writer in the Lancet said (1872, II), " Year by year fresh bands of students came to imbibe from his lips the instruction which their predecessors had abandoned with reluctance, till his academic progeny knew no distinction of race or even color, but coalesced into a noble band of enthusiasts in the cause of medicine, of science and of humanity." In this academic progeny Louis' American pupils take a very unusual position. Among the thousands in the profession of this country who have during this century sought light and learning in the older lands, the group of young men who studied in Paris, between 1830 and 1840, had no predecessors and have had no successors. Partly because the time was ripe and they were active agents in bringing the new art and science to the New World, partly owing to inherent capabilities, etc., but not a little because the brightest minds among them fell under the influence of Louis — they more than any others gave an impetus, which it still feels, to the scientific study of medicine in the United States.

There had been, of course, in Paris many students from this country prior to 1830, but they do not form a school, recognizable to us at present. One name comes to my mind, that of the Rhode Island philosopher, Eiisha Bartlett, a jjeripatetic of the peripatetics, in the days when men moved from city to city, like the Sophists of ancient Greece. I do not know whether when in Paris in 1828 he came personally under Louis' influence— probably not, as Louis spent part of that year in Spain — but he brought back recent French methods, with Gallic lucidity and a keen appreciation of the value of the numerical method. His well known work on Typhus and Typhoid Fever, issued in 1842, is in itself a lasting witness to the intelligence and progressive character of the younger teachers of that day. With a clear separation of Typhus, Typhoid, the Periodic and Yellow Fevers, it had at the date of its publication no counterpart in Eurojiean literature, and is in remarkable contrast to the chaotic treatises of Armstrong, Fordyce, Tweedie, Southwood Smith and othei'S.

Without attempting to give a comjilete list, the following were among the American students in Paris between 1830 and 1840:

From Boston, James Jackson, Jr., H. I. Bowditch, Oliver Wendell Holmes, Geo. 0. Shattuck, Jr., John D. Fisher, J. C. Warren (then past middle age), and J. Mason Warren.

From New York, John A. Swett, Abraham Dubois, Alonzo Clark, Charles L. Mitchell, Charles D. Smith, Valentine Mott, Sr., and John T. Metcalf.

From Philadelphia, Geo. W. Norris, W. W. Gerhard, Casper W. Pennock, Thomas Stewardson, Alfred Stille, Thomas D. Muter, J. Campbell Stewart, Charles Bell Gibson, John B. Biddle, David H. Tucker, Meredith Clymer, Wm. P. Johnston, W. S. W. Itusheuberger, Edward Peace, William Pep2)er, Sr.

Fi-om Baltimore, William Power.

From the South, Peter C. Gaillard, Gibbs, and Peyre Porcher of Charleston ; J. L. Cabell, L. S. Joyues, Selden and Randolph of Virginia.

" And many more whose names on earth are dark " — men of the stamp of Dr. Bassett of Alabama, who felt the strong impulsion to know the best that the world offei'ed, every one


of whom has left a deep and enduring impression in his sphere of work.

It would be impossible to tell in detail how Louis' students brought back his spirit and his methods to their daily work, and of the revolution which they gradually effected in the study and in the treatment of disease. I can best, perhaps, fulfill my object by referring somewhat fully to two of the most distinguished among them, James Jackson, Jr., and W. W. Gerhard.

James Jackson, Jr., is the young Marcellus among the physicians of this country, "the young Marcellus, young, but great and good." I do not know in our profession of a man who died so young who has left so touching a memory. He was the son of Dr. James Jackson, of Harvard, one of the most distinguished of New England's physicians, a man to whom our generation owes a heavy debt, since he, with Jacob Bigelow, was mainly instrumental in bringing about more rational ideas on the treatment of disease. Of Louis' pupils from this side of the water, young .lackson seems to have been his special favorite. After taking the B. A. degree at Cambridge in 1828, Jackson attended the medical lectures at Harvard, and in the spring of 1831 went to Paris, where he remained until the summer of 1832. Returning home in 1833, he graduated in medicine at Harvard in 1834. In the two years and a half of his studies in this country before going abroad he had had exceptional opi)ortunities with his father at the Massachusetts General Hospital, and showed his early industry and ability by taking one of the lioylston Prize Essays before the completion of his second year of study.

In Paris he attended the practice of La Pitie and St. Louis. He soon became devoted to Louis, and by him was utilized to the full in the cholera epidemic in 1832. Two letters from Louis to James Jackson, Sr., show how important he thought a prolonged period of study was for a young man. He says: " I pointed out to him (James Jackson, Jr.) the advantage it would be for science and for himself if he would devote several years exclusively to the observation of diseases. I now retain the same opinion and am strengthened in it; for the more T become acquainted with, and the more I notice him applying himself to observation, the more I am persuaded that he is fitted to render real service to science, to promote its progress. I find that he would be well pleased to follow for a certain period the vocation for which nature has fitted him ; but he has stated to me that there are many difKculties which would prevent his devoting himself exclusively to observation for several years. But can these difKculties be insurmountable?"

xVud again : " Let us sup2)ose that he should pass four more years without engaging in the practice of medicine, what amass of positive knowledge will he have acquired! How many important results will he have been able to publisli to the world during that period ! After that he must necessarily become one of the bright lights of his country; others will resort to him for instruction, and he will be able to impart it with distinguished honor to himself. If all things be duly weighed, it will appear that he will soon redeem the four years, which men of superficial views will believe him to have lost." In another letter, the following year, just before young


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Jackson's departure from Paris, he refers again to this question and urges Dr. Jackson to allow his son to devote himself exclusively to observation for several years in Boston. The extract from this letter is worth quoting. "Think for a moment, sir, of the situation in which we physicians are placed. We have no legislative chambers to enact laws for us. We are our own lawgivers ; or rather we must discover the laws on which our profession rests. We must discover them and not invent them ; for the laws of nature are not to be invented. And who is to discover these laws? Who should be a diligent observer of nature for this purpose, if not the son of a physician, who has himself experienced the difficulties of the observation of disease, who knows how few minds are fitted for it, and how few have at once the talents and inclination requisite for the task ? The inclination especially, for this requires that the observer should possess a thorough regard for truth, and a certain elevation of mind, or rather of character, which we rarely meet with. All this is united in your son. You ought — for in my opinion it is a duty — you ought to consecrate him for a few years to science. This, sir, is my conviction, and I hope it will be yours also. I know very well that every one will not be of the same opinion ; but what matters it, if it be yours ? — if you look upon a physician, as I do, as holding a sacred office, which demands greater sacrifices than are to be made in any other profession."

Young Jackson's letter to his father, just as he was quitting Paris, indicates on what affectionate terms he had lived with Louis. " In two hours I am out of Paris. I will not attempt to describe to you the agony it gives me to quit Louis. He is my second father, and God knows that is a name I of all men cannot use lightly. I may not persuade you to look upon him with my eyes exactly as a scientific man ; but in your heart he must have the share of a brother; for he almost shares my affection with you. From one upon whom I had no claims but those which my life and mind and habits gave me, I have experienced a care, an affection which I never could dare expect from any but my dear father, and which I shall ever feel to be the most honorable and truly worthy prize of my life."

He seems to have inspired the same tender feelings in all his American students. In the Memoir of Dr. Bowditch, to which I have already referred, he speaks of Louis' fatherly kindness to him during a prolonged attack of rheumatic fever lasting for many weeks.

Young Jackson was one of the founders, in 1833, of the Society for Medical Observation, which consisted of the ablest of the students of Louis, Chomel and Andral. During his stay in Paris he made an important study of cholera, which was published in this country in 1833. It was most timely, as it gave the profession here a very clear and accurate description of the disease, of which up to that time they had had no experience. Jackson's name, too, will always be associated with the studies upon emphysema, and he is the discoverer of the prolonged expiration in early pulmonary tuberculosis.

Returning to Boston in the autumn of 1833, he spent the winter preparing for his degree and elaborating the notes which he had taken in Paris. In March he fell ill with a dysentery, which proved fatal on the 37th of the month, in the


twenty-fifth year of his age. I know of no young man in the profession who had given pledges of such exceptional eminence. His influence in extending Louis' methods and views throughout New England was chiefly through his father, who, though a man approaching his sixtieth year, became an ardent follower of Louis and the numerical method.

In Oliver Wendell Holmes' recently issued Biography you will find a delightful description of life at the Medical School of Paris at this period. He bears witness to the good effect which Jackson's warm friendship with Louis had had in promoting the interests of American students. I may conclude with a quotation from Dr. Jackson's, Sr., memoir: "At the suggestion and request of one of my most judicious brethren I shall add that my sou's influence on the profession here, in the short time he was with us, was of a very salutary description. This gentleman states that my son not only caused others, who had not yet read the works of M. Louis, to study them with care, but that he induced among the rising members of the profession in our own city the habits of thorough observation of the phenomena of disease in the living and in the dead, which he had learned from the same great pathologist. He also taught us much in respect to the physical signs of disease in the thorax, with which we were imperfectly acquainted before; at least I may say this was true as to myself. Indeed I ought to say more, for he aided me very much in regard to the diagnosis of the more obscure diseases of that region, derived from the combination of the physical and rational signs. On emphysema of the lungs he threw, for me, quite a new light."

Wm. W. Gerhard was the most distinguished of the American pupils in Paris between 1830 and 1840. When you call to mind the men whom I have mentioned, this may seem a strong statement, but I feel certain that could we take their suffrages they would accord him the place of merit in consequence of the character of his work. Dr. Gerhard was born in Philadelphia, in 1809, and was graduated from the University of Pennsylvania in 1831. Early in the year he went to Paris and attached himself to Louis at La Pitie. In one of his letters* to his brother, dated January 18, 1833, he says: "Dr. Louis is delivering an interesting clinic at La Pitie ; he is a remarkable man, very different from the physicians of Eni^land or America, and remarkable even at Paris by the strict mathematical accuracy with which he arrives at his results ; he is not a brilliant man, not of the same grade of intellect as his colleague at La Pitie, Andral." In another letter he gives an account of his day's work. "The morning from seven to ten is occupied with the visit and clinic at the hospital ; there are several distinct clinics now in actual proo-ress; each of them has its advantages. I shall vary my attendance at the different hospitals and select those lecturers who are of real merit. At this moment we are following ing Piorry at the SalpetriOre, a very distant hospital, two or three miles from our lodgings; his patients are all old women, and not interesting. My object in following his course is to obtain some interesting information on the best mode of


  • I am indebted to members of Dr. Gerhard's family for the letters

from which these extracts are taken.


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investigating the diseases of the chest. M. Piorry has devoted special attention to this subject. From Salpetriere we hurry to La Pitie; we hear a surgical lecture, reach home to breakfast, and then to the school of medicine. The lectures at the school, with a private course of anatomy during the hour of intermission, fill up the remainder of the day until four. Fortunately a private clinic at La Charite introduces me to a set of very interesting cases, especially on pectoral cases. Dr. Dagueau has a class who pay him ten francs a month and enjoy the privilege of examining the patients much more conveniently than is practicable during the morning visit in the midst of a crowd of students. We dine at five-thirty and then lectures again until eight o'clock. Imagine the facilities, the delightful advantage of acquiring positive information, and what is at least as important, of learning the mode of obtaining these positive results. We see and hear the men who are so well known to us in America, learn to form a correct estimate of their relative worth — in short, one of the most striking advantages of a medical visit to Europe is to acquire the sort of liberal professional feeling which is rarely secured by the continued intercourse with the same men, and the unpleasant medical politics which divide the profession in America."

Evidently Broussais made no special impression on Dr. Gerhard. He says, " Broussais is the best known, his reputation is universal, and the benefits he has conferred on medicine are immense, but unfortunately he is a wretched lecturer. His own opinions are given in the most awkward, clumsy manner; the manner and style of lecturing are coarse and vulgar."

In another letter of February 3, 1833, he tells how he induced Louis to give them private instruction. To his brother he writes : " I must write you at least a few days before the excitement has passed off : can you imagine how fortunate I am — devinez si vous pouvez— two or three days ago, Jackson, Pennock and myself were talking of hospitals and morbid anatomy, when the idea occurred of attempting the study of pathology in a particular manner. It was this: to obtain the specimens and study them, the authors in our hand, exactly and carefully comparing authorities with the subject before us. We addressed ourselves to two of the internes at La Pitie attached to the salles of Louis and And-ral, and they agree to procure all facilities in their power and communicate their own information for the compensation of 60 francs from each of us ; we accordingly visit La Pitie on three afternoons of the week and examine the parts at the hospital, afterwards carrying home such portions as require minute investigation. Our first success in this opening of new sources of instruction emboldened tis to attempt something of higher importance. We were all desirous of studying auscultation, of studying it in such a manner as to be sure of our ground on our return, and to be capable of appreciating the advantages of the art. Louis' public instructions were valuable, but his private lessons upon a subject demanding minute and patient inquiry we knew would be infinitely moi'e so. I therefore in the name of my friends addressed him a polite note, accomjianied by a handsome pecuniary offer; we did this with little hopes of success, but happily for us he accepted our proposition, and next week we are his private pupils at La Pitie. We are, I


believe, the first who have made this arrangement with M. Louis, and you may estimate its importance when I tell you that he is considered in excellence of diagnosis the successor of Laennec. Our advantages for the study of pathology and the diagnosis of diseases of ttie chest are now superior ; they are indeed the very best in the world, and our eagerness to embrace them will, I hope, render them of real utility ; of course they involve an additional expenditure of 400 or ."300 fr., but I should be happy to shorten my stay at Paris a mouth to improve the remainder of my time in this manner, if such were necessary for me. Pennock and myself are very happy to have become intimate with .Jackson ; he has superior talents, and his excellent education, conducted by his father, unquestionably the first physician in America, has cultivated his mind and developed an ardent attachment to medicine."

Few American students have occupied their time abroad to greater purpose than Dr. Gerhard. He appears to have been an indefatigable worker, and the papers which he published based upon material collected in Paris are among the most important which we have from his pen. Thus with Pennock he described Asiatic cholera in 1832. Devoting himself particularly to the study of diseases of children, he issued a very interesting paper on small-pox, and two papers of very special value, the first on tuberculous meningitis and the other upon pneumonia in children. Both of these papers mark a distinct point in our knowledge of these two diseases. He is usually accorded the credit of the first accurate clinical study of tuberculous meningitis.

Late in the year 1833 he returned to Philadelphia, and at his suggestion his friends had secured him the appointment as resident physician at the Pennsylvania Hospital, which he took early in 1831. This step indicated how carefully he had weighed the important influence in Louis' career of the years of quiet work at La Charite. At the Pennsylvania Hospital he had an opportunity to study the common continued fever of the country, and determined that it was identical, clinically and anatomically, with the typhoid fever of Louis, and characterized by a special lesion in the glands of Peyer. I do not know exactly how long he remained resident physician at the Pennsylvania Hospital, but he was soon after appointed one of the physicians at Blockley, and here in 1836 he was able io carry out his most important piece of work. The general opinion prevailed that the fever which Louis described and which had the lesions in the small bowel was only a modification of the ordinary typhus fever which at that time prevailed so extensively, particularly in Great Britain and Ireland. In London, Edinburgh and Dublin the intestinal lesions were regarded as only accidental, and not indicative of a special affection. Dr. Gerhard knew the typhoid fever of Louis well, and had had an opportunity of studying it again at the Pennsylvania Hospital, so that when the epidemic of typhus fever developed in 1836 he was in a very good position to make an accurate study of the disease. Two hundred and fourteen cases were observed, and as a result of his study he declared positively that the typhus fever, which was similar to the disease which he had also seen in Edinburgh, was a different affection altogether from the typhoid fever with intestinal lesions. These observations, vou must remember.


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were made in 1836, at a time when the greatest confusion existed as to the forms of fever. It took a great many years in Great Britain before the duality of the prevalent fever was recognized, but owing to the influence of Gerhard's paper, and to the accurate knowledge of fever brought to this country by Louis' pupils, the differentiation of the two diseases was here quickly recognized, since, as already mentioned, Bartlett in 1812 considered them apart.

Gerhard's work influenced his Paris friends greatly, and this was strengthened by the papers read before the Society for Medical Observation by Geo. C. Sbattuck and Alfred Stille, of whom the former had had opportunities of studying typhus fever in Great Britain, while the latter had been one of Gerhard's house physicians in the typhus epidemic at Blockley. Shattuck's paper is published in the Medical Examiner for 1840. I have always regretted that Dr. Stille's paper has never appeared in print. He was kind enough to let me see it, and, as I have mentioned elsewhere, the differential points between typhus and tyi^hoid fever are nowhei-e more clearly laid down.

The University of Pennsylvania early took advantage of Gerhard's training and utilized him as clinical lecturer at the Philadelphia Hospital. He soon acquired a special reputation in diseases of the heart and lungs. In 1842 appeared the first edition of his work on Diseases of the Chest, which ran through four editions, and is still a valuable work of reference. One of his fellow-students in Paris, Stewardson, has given a very pleasing picture of him as a clinical teacher : " As a clinical teacher he was remarkably successful and exerted a powerful and commanding influence. Without any pretension to eloquence, he nevertheless riveted the attention of his hearers and stimulated their enthusiasm. Himself deeply interested in bis subject, he communicated this interest to his audience by the sheer force of truth. Students saw that truth was his object, not display ; the advancement of science, and not the gratification of personal feelings, whether of vanity or ambition; in short, that in his mind, a deep interest in his subject and a thorough conscientiousness in the pursuit of it were the overmastering motives. In an easy and conversational


style he presented to his hearers a graphic portraiture of the case before them, bringing into relief its most important symptoms; impressing upon their minds the most striking features in its history; pointing out, by a few clear and practical expressions, the bearing of any particular fact upon interesting medical questions, but avoiding long and labored arguments, or general disquisitions upon the nature of diseased action. He neither stimulated the fancy by the flowers of rhetoric, nor amused the intellect with episodes upon theoretical questions, but confined himself to drawing such practical conclusions as were clearly deducible from the facts presented. No man of his day enjoyed so high a reputation as a clinical teacher, and not only did he succeed in an eminent degree in arousing the enthusiasm of students and putting them in sympathy with himself, by infusing into them his own ardor in his favorite study ; but he produced an influence upon the profession here which is felt still, which has fostered the establishment of clinical teaching among us, and done much to give it that rank which it now occupies here as a branch of medical instruction."

Of the work of Louis' other students in this country time would fail me to tell — of the influence of Bowditch, Holmes and Shattuck in Boston, of Swett, Clark and others in New York, of Pennock, Stewardson, Stille in Philadelphia, and of Power in Baltimore. To them all we owe a heavy debt of gratitude. They brought from Paris enthusiasm, faith in the future, faith in the profession of their choice, accurate methods and a loyal love of truth. Endowed with the spirit and zeal of their master, they carried his great message to the New World ; and more than this, touched with those finer qualities which made Louis so lovable, they have become bright ideals for all future generations of American students.

There remain, so far as I know, three only of the Paris students of whom I have spoken, John T. Metcalf, Meredith . Clymer, and your honored patron, Alfred Stille. They, too, must soon go the way of all the earth ; but among the consolations of old age what greater solace can they feel than that the lives of the men whose fathers and grandfathers they taught are still made better by their presence.


WILLIAM HARVEY AS AN EMBRYOLOGIST.*

By William K. Brooks, LL. D., Professor of Zoology, Johns Hoiikins JJniversUy.


The immortal discoverer of the circulation of the blood is held to be also the discoverer of the law of embryology — "that all animals are produced out of ova" (Encyc. Brit., 9th ed., art. Embryology, p. 164); and he is also held to have had some vague premonition, scarcely worth mentioning in history, of the great law that the complex animal arises, from a relatively homogeneous germ, by gradual differentiation or epigenesis.

I hope to show, by quotations from his work on embryology (Exercitationes de Generatione Animalium, Amstelodami,


■ Read before the Johns Hopkins Historical Club, February, 1897.


1651, translated into English by Robert Willis, M. D., London, 1848), that both these current impressions are erroneous. He not only formulated but demonstrated epigenesis. liis statement of this law is clear, definite and thoroughly modern, and it is based upon actual observations which are fully described.

On the other hand the conception which he sought to express by the dictum "omne vivum ex ovo" is totally foreign to the principles of modern embryology. Harvey was a worker, not a dreamer, and his dictum is no mere guess or happy inspiration. It sums up results reached by laborious research, and as a generalization based on actual study it still has value,


although its meaning has nothing in common with tliat which the words have as we now use them. He repudiates in most energetic language the opinions, current at his time, which come nearest to the modern discovery that the physical continuity of living matter is never broken. In fact the chief aim of his treatise is to show that his observations, as he interpreted them, prove that there is no physical or " corporeal " continuity between parent and child.

Embryologists who permit Germans to write the history of their science, and make no protest when the demonstration that the embryo arises from the egg by epigenesis is attributed to Wolff (1759), and to Von Baer (1839), are either ignorant of Harvey's researches (1651) or indifferent to the fame of this great Englishman, who studied the history of the chick as laboriously and faithfully as Von Baer, nearly two hundred years before. While his resources were more limited, his ability to reflect upon the meaning of his observations and to state in clear and energetic words the results of his " Beobachtung und Eeflexion," were inferior in no way to those of the justly famous author of the "Entwickeluugsgeschichte der Thiere."

Harvey means just what more modern writers mean by "epigenesis," but the strangeness of the views he opposed gives us difficulty. The form of words into which an account of a scientific discovery falls is fixed by the view of the matter which is current at the writer's day, and later generations of readers may be puzzled by inability to occupy his standpoint. Thus it is with Harvey, and we thus explain the prevalence of the opinion that he had no more than a dim adumbration of truths the demonstration of which is generally credited to Wolff and Von Baer.

The evolutionary teachings of Bonnet are quite intelligible to us; and as we easily put ourselves in Von Baer's place, his refutation of Bonnet appeals to us with all its native force; but it is much harder for us to stand where Harvey stood.

So far as I can discover, no notion at all equivalent to Bonnet's conception of germs ever entered Harvey's mind or the mind of any one before his time. He presents the evidence for epigenesis as opposed, not to "evolution," but to "metamorphosis," and his way of using the last word is so unfamiliar to us that we cannot grasp what he has in mind without effort.

They who studied embryology before him held one modification or another of the very ancient belief that embryos arise from "excrement"; that they are products of decomposition.

He gives the evidence for epigenesis as opposed to this opinion which finds no pigeon-hole in the modern mind. Fortunately he is a ready writer. Hlustrations and analogies overflow his brain and pen; and patient study enables us to pick out passages which give his views on epigenesis uncomplicated by reference to " metamorphosis." When we have done this we find his reasoning as modern and definite as that of Von Baer, although his resources did not qualify him to sum up the evidence with modern exhaustiveness.

While Harvey does not deny that some " imperfect " animals may be genei-ated "out of a putrescent material, the drying of a moist substance, or the moistening of a dry one," he tells us, clearly and definitely enough, that the generation of all "per


fect " animals, such as the lion and the cock, " is the result of epigenesis as the man proceeds from the boy; the edifice of the body, to wit, is raised on the punctum saliens as a foundation ; as a ship is made from the keel, and as a potter makes a vessel . . . For out of the same material from which the first part of the chick or its smallest particle springs, from the very same is the whole chick born ; whence the first little droji of blood, thence also proceeds its whole mass by means of generation in the egg ; nor is there any difference between the elements which constitute and form the limbs or organs of the body, and those out of which all their similar [i. e. homogeneous] parts, to wit, the skin, the flesh, veins, membranes, nerves, cartilages, and bones derive their origin. For the part that was at first soft and fleshy, afterwards, without any change in the matter of nutrition, becomes a nerve, a ligament, a tendon ; what was a simple membrane becomes an investing tunic ; what had been cartilage is afterwards found to be a spinous process of bone, all variously diversified out of the same similar [homogeneous] material." From what "appears to be homogeneous in the beginning and resembles the spermatic jelly" the structure of the body arises; its parts being "at first delineated by an obscure division, and afterwards become separate and distinct organs."

He says the result of the process of development is just as if the chick were created by a command to this effect: " Let there be a similar [homogeneous] colorless mass, and let it be divided into parts and made to increase, and in the meantime, while it is growing, let there be a separation and delineation of parts ; and let this part be harder and denser and more glistening, that be softer and more colored."

" Now it is in this very manner that the structure of the chick in the egg goes on from day to day; all its parts are formed, nourished and augmented out of the same material. . . . For there is a greater and more divine mystery in the generation of animals than the simple collecting together, alteration and composition of the whole out of parts would seem to imply; inasmuch as here the whole has a separate constitution and existence before its parts, the mixture before the elements."

These passages summarize conclusions from observations which have been more fully described in forty-four preceding chapters or "exercises," and it would be difficult, even at the present day, to state in more definite language the truth that the developing embryo passes " from indefinite, incoherent homogeneity to definite, coherent heterogeneity by successive integrations and differentiations."

While we have no desire to ignore the merits of Wolff or to belittle the greatness of Von Baer, we find it hard to understand how any one who knows Harvey's works can, without protest, read this assertion or similar ones in the German works from which it is derived:

" It was reserved for Caspar Frederick Wolff, a German by birth ... to bring forward observations which . . . established the theory of epigenesis upon the secure basis of ascertained facts" (Encyc. Brit., 9th ed.. Embryology, 1(35).

We now know that the germ itself is an organism of wonderful complexity ; that its homogeneity is relative, not absolute ; but there is great mystery to us as well as to Harvey in the


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manner in which " the whole has a separate constitution and existence before its parts," and while the doctrine of "metamorphosis " as held in Harvey's day has vanished from science, I venture to believe that we shall Knd in his discussion of this doctrine, clear statement of other difficulties which are still as grave as he found them.

It is hard to decide just what his opinion on spontaneous generation was. No less careful a student than Huxley tells us (Encyc. Brit., 9th ed., art. Evolution, p. 746) that "Harvey believed as implicitly as Aristotle did in the equivocal generation of the lower animals." "Harvey shared the belief of Aristotle — whose writings he often quotes, and of whom he speaks as his precursor and model, with the generous respect with which one genuine worker should regard another — that such germs may arise by a process of 'equivocal generation' out of non-living matter."

1 am by no means confident that this assertion does justice to Harvey, or that the quotations from Aristotle prove anything except that Harvey was not yet quite prepared to demonstrate their error. I believe there is ample evidence that he had made many observations which, while he never published them, led him to distrust most of the familiar examples of spontaneous generation, although he may not have been fully armed to attack the teachings of " my leader," Aristotle, "one of nature's most diligent inquirers," "whose authority has such weight with me that I never think of differing from him inconsiderately." It is true that he quotes without comment, and occasionally without credit, many passages in which Aristotle affirms sjjontaneous generation ; but as an offset to this he tells us explicitly (Exercise the forty-first) that he shall show in another place " that many animals, especially insects, arise and are propagated from elements and seeds so small as to be invisible (like atoms flying in the air), scattered and dispersed here and there by the winds ; and yet these animals are supposed to have arisen spontaneously, or from decomposition, because their ova are nowhere to be found." He was far too cautious to have ventured to criticise " the philosopher," even to this extent, without pretty good evidence; and in Exercise the sixty-ninth he tells us why this evidence was never published. "Let gentle minds forgive me," he asks, "if, recalling the irreparable injuries I have suffered, I here give vent to a sigh. This is the cause of my sorrow: — whilst in attendance on his majesty the king, during our late trouble and more than civil wars, not only with the permission but by the command of the Parliament, certain rapacious hands stripped not only my house of all its furniture, but, what is subject of far greater regret with me, my enemies abstracted from my museum the fruits of many years of toil. Whence it has come to pass that many observations, parlictilarly on the generation of insects, have perished, with detriment, I venture to say, to the republic of letters."

Is there not reason to believe that, if they are ever discovered, those lost observations will be found to cover some of the ground which was so successfully explored by Spalanzanni more than a hundred years later ?

Harvey's reference (Exercise the twenty-seventh) to " the animalculae which are engendered in our bodies . . . lumbrici,


ascarides, lice, nits, syrones and acari," and to " the worms which are produced from plants and their fruits, as from gallnuts, the dog-rose, and various others," might be held to imply belief in heterogenesis, if he did not tell us, almost immediately, that: "It certainly cannot be that the living principles of these animals which arise in the gall-nuts existed in the oak, although these animals live attached to the oak and derive their sustenance from its juices."

Notwithstanding Huxley's opinion, Harvey seems to have been nearer than any of his successors for a hundred years to the modern discovery that all living things come from germs, although I shall show soon that he did not intend to imply anything at all like the modern view by his statement that this is true.

In his discussion of epigenesis as contrasted with " metamorphosis," he assumes the reality of " equivocal " generation, as he does in many other places, although, in view of the passages I have quoted, I believe that this is admitted out of courtesy to Aristotle, and for the sake of the argument, as something which he is not yet fully prepared to disprove.

He tells us (Exercise the forty-fifth) that there are two ways in which one thing may be made out of another. When a workman cuts the material already prepared, divides it and rejects what is superfluous, till he leaves it in the desired shape, as in nuiking a statue from a block of stone, the whole material of the future piece of work has already been in existence before it is finished into form or any part of the work is yet begun. AVhen on the other hand a potter educes a form out of clay by the addition of parts, increasing its mass, and giving it a figure, at the same time that he provides the material, which he prepares, adapts and applies to his work, "the form may be said rather to have been made than educed." " So exactly it is with regard to the generation of animals. Some, out of a material previously concocted and that has already attained its bulk, receive their forms and transfigurations ; and all their parts are fashioned simultaneously, each with its distinctive characteristics, by the process called metamorphosis, and in this way a perfect animal is at once born; on the other hand, there are some iu which one part is made before another, and these from the same material afterwards receive at once nutrition, bulk and form ; that is to say, they have some parts made before, some after others, and these are at the same time increased in size and altered in form. The structure of these animals commences from some one part as its nucleus and origin, by the instrumentality of which the rest of the limbs are joined on, and this we say takes place by the method of epigenesis, namely by degrees, part after part; and this is, in preference to the other mode, generation properly so called. In the former of the ways mentioned, the generation of insects is effected when by metamorphosis a worm is born from an egg ; or out of a putrescent material, the drying of a moist substance or the moistening of a dry one, rudiments are created from which, as from a caterpillar grown to its full size, or from an aurelia, springs a butterfly or fly already of a proper size, which never attains to any larger growth after it is first born. But the more perfect animals with red blood are made by epigenesis or the superposition of parts. In the former, chance or hazard seems the principal promoter of gen


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eration, aud the form is due to the potency of a pre-existing material ; and the first cause of generation is 'matter ' rather than an ' external efficient,' while the more perfect animals owe their immortality to one constant source — the perpetuation of the same species . . . Bees, wasj^s, butterflies, and whatever is generated from caterpillars by metamorphosis, are said to have sprung from chance, aud therefore to be not preservative of their own race. . . . The lion and the cock owe their existence, as it were, to nature, or an operative faculty of a divine quality, and require for their propagation an identity of species, rather than any supply of fitting material." " In the generation by metamorphosis forms are created as if by the impression of a seal, or as if they were adjusted in a mould . . . but an animal which is created by epigenesis attracts, prepares, elaborates, and makes use of the material all at the same time. The processes of formation aud growth are simultaneous. In generation by metamorphosis the whole is distributed and separated into parts, but in that by epigeuesis the whole is put together out of parts, in a certain order, and constituted /ro?» them. In the one case the result is due to matter ; in the other the animal makes itself.

" Now it appears clear from my history that the generation of the chick from the egg is the result of ejjigenesis rather than of metamorphosis, and that all its parts are not fashioned simultaneously, but emerge in their due succession and order; it appears, too, that its form proceeds simultaueously with its growth, aud its growth with its form; also that the generation of some parts supervenes on others previously existing, from which they become distinct; lastly, that its origin, growth aud consummation are brought about by the method of nutrition.

" The formative faculty of the chick rather acquires and prepares its own material than only finds it when prepared, aud the chick seems to receive its growth from no other than itself. And as all things receive their growth from the same power by which they were created, so likewise should we believe that the chick is created by the same power by which it is preserved and caused to grow."

The meaning of this rather puzzling passage will be somewhat clearer after we have examined Harvey's views on generation, but when we omit the complications which come from the reference to "metamorphosis," its meaning as interpreted by the rest of the essay is about as follows :

The substance which composes the body of all "perfect" animals does not exist as such before the body itself is formed; but it consists of unorganized or "homogeneous " food which is changed by nutrition into all the diversified parts of the complicated body, so that nutrition, growth aud development go on together. As the organized body is constructed by the assimilation of unorganized food, its structure cannot be the outcome of the ordinary or physical properties of this food. There must be some organizing iufiuence at work making use of these properties to construct out of homogeneous matter a definite organism belonging to the same species with the parents. To the question what this organizing influence is, he answers that this is a " divine mystery," or, in plain English, that he does not know, although he finds clear evidence of its existence. He says in many places that the egg has a ■' vital principle," but the context shows that he means


by this no more than we mean when we say it is " alive," and nothing is farther from his thoughts than recourse to supernatural agencies, for he tells us clearly that while the cause of its development is a " divine mystery," " the egg is a natural body endowed with animal virtues ... it is moreover a body which under favorable circumstances has the capacity to pass into an animal form; heavy bodies, indeed, do not sink more naturally, nor light ones float, when they are unimpeded, than do seeds aud eggs in virtue of their inherent capacity become changed into vegetables aud animals." (Exercise the twenty-sixth, p. 373.)

It would be a gross error to infer, from this passage or from others like it, any further similarity between Harvey's opinions aud the results of moderu microscopic study of ova and male cells. In order to understand the meaning of his celebrated dictum " omne vivum ex ovo " we must undertake more extended analysis of his observations aud reflections on generation, aud of the opinions of his predecessors.

Aristotle saw nothing strange or exceptional in the generation of animals from decomposing organic matter, for he believed that all generation takes place in essentially the same way ; and he regarded the generation of insects from putrescent slime as a simple or typical example, what we should now call a primitive type, of generation in general, in comparison with which more complicated instances are to be interpreted.

As a bloody substance is discharged at intervals from the reproductive organs of woman, during the fertile period of her life, and as its apjiearance marks the beginning and its cessation the end of fertility, he believed that the mammalian embryo is formed out of this substance just as other animals are generated from decomposing matter of other kinds.

" Milk aud the menstrual discharge," he tells us (De Gen. II, i), " are of the same nature." " When the semen masculinum enters the female uterus it coagulates the purest part of the catamenia," aud when this has " set in the uterus " it forms a coagulum like curdled milk. As heat causes milk to curdle, so " the semeu or geniture of the male bears the same affinity to the nature of the catamenia " aud causes it to " set " without itself contributing any part of the substance of the coagulum. " The female always supplies the matter, the male the power of creation, and this it is which constitutes one male and another fenuile." "The male is the efficient agent, aud by the motion of his geniture creates what is intended from the matter contained in the female." " The body and the bulk therefore are necessarily supplied by the female; nothing of the kind is required from the male; for it is not even requisite that the instrument, nor the efficient agent itself, be present in the thing that is produced. The body then proceeds from the female ; the life (anima) from the male."

Harvey points out the inconsistency of Aristotle's admission that hybrids "partake of the species of both parents" (De Gen. Anim. II, 3), and his assertion that '• the conception or egg receives '" "from the feuuile its body solely and its dimensions," and that the mother has no part in the trausmissiou of "form, species and life"; for the studj" of jiybrids shows the error of his opinion that creative force or vital power is


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derived exclusively from the male, and proves that both parents must be efficient in determining form or species.

The medical men of Harvey's day held a different opinion, as he tells us iu Exercise the thirty-second. Like Aristotle, they held that the embryo arises from "excrement"; but they held, in opposition to his teaching, " that the prime matter of conception is not blood, but the mingled geuitures of both sexes." They also held, iu opposition to Aristotle, the opinion, which Harvey shares, that the male is no more " the efficient cause of generation " than the female.

"Conception, according to the opinion of medical men, takes place in the following way: during intercourse the male and female dissolve in one voluptuous sensation, and eject their seminal fluids (geniturae) into the cavity of the uterus, where that which each contributes is mingled with that which the other supplies, the mixture having both equally the faculty of action and the force of matter; and according to the predominance of this or that geniture does the progeny turn out male or female. It is further imagined that immediately after the intercourse something of the conception is formed iu the uterus."

If the uterus contains a " conception " immediately after a fertile union, in the form of a bloody coagulum, as Aristotle supposes, or iu the form of the mingled emissions or geuitures of both sexes, as the medical men taught, this ought to be discoverable, and Harvey, a true scientific investigator, set himself to hunt for it without a microscope.

His facilities for making the search, and its results, are best described in his own words. He was the attending physician of the King of England, and he tells us : " It was customary with his Serene Majesty, King Charles, after he had come to man's estate, to take the diversion of hunting almost every week, both for the sake of finding relaxation from grave cares and for his health; the chase was principally the buck and the doe, and no prince iu the world had greater herds of deer. This gave me an opportunity of dissecting these animals almost every day during the whole of the season when they were rutting, taking the male and falling with young. I had occasion so often as I desired it to examine and study all their parts, particularly those devoted to the offices of generation."

His studies upon the development of the embryo of the deer are fully described at length in the essay on generation, but only those which relate to the question of conception concern us at present. Here his researches had a very definite result, "llepeated dissections performed in the course of the month of October, both before the rutting season was over and after it had passed, never enabled me to discover any blood or semen or a trace of anything else, either in the body of the uterus or its cornua." Neither the bloody coagulum of Aristotle nor the geniture of the medical men has any existence. The "conception" which should be discoverable iu the uterus if their teachings are correct, cannot be found there when a search is made for it, and actual observation shows that their teachings are erroneous and fanciful.

The keepers and huntsmen said " that I was both deceiving myself and had misled the king, and that there must of necessity be something of the conception to be found in the uterus. These men, however, when I got them to bring their


own eyes to the inquiry, gave up the point." Harvey tells us that the king fully appreciated the value of the investigation, and in order " that this important question might be the more satisfactorily settled in all time to come," provided means for isolating the does and for proving that there was no error as to the fact of conception ; but the physicians were still unconvinced, and "held it among their impossibilities that any conception should ever be formed without the presence of the semeu masculinum, or some trace remaining of a fertile intercourse within the cavity of the womb." But the man who had proved the error of their teachings regarding the function of the heart and blood-vessels had little tolerance for their belief iu anything which they were unable to demonstrate.

If they had insisted that Harvey's resources were inadequate, that the "conception" for which he sought is too minute to be found by such rough means, we now know they would have been in the right, for even at the present day our knowledge of the essential facts of mammalian conception is, for the most part, a deduction from observations on the eggs of animals which were almost or quite uuknown to Harvey, the sea-urchin and ascaris, for example. But his proof of the non-existence, in the uterus of the doe, of anything corresponding to their teachings is conclusive. He did not stop here, however, for he tells us: " In the dog, rabbit and several other animals, I have found nothing iu the uterus for several days after intercourse ; I therefore regard it as demonstrated that after fertile intercourse among viviparous as well as oviparous animals there are no remains in the uterus either of the semen of the male or of the female emitted in the act; nothing produced by any mixture of these two fluids, as medical writers maintain, nothing of the menstrual blood present as 'matter' iu the way Aristotle will have it; in a word, that there is not necessarily even a trace of the conception to be seen immediately after fruitful union of the sexes. It is not true, consequently, that in a prolific connexion there must be any prepared matter in the uterus, which the semen masculinum, acting as a coagulating agent, should congeal, concoct and fashion or bring into a positive genei'ative act."

His study of the generation of birds leads him to the same result. "As the hen does not emit any seminal fluid, and as the seminal fluid of the cock does not reach the uterus of the heu, and as there is no trace of an egg to be found in the uterus immediately after intercourse, it is obvious that it is not engendered" by the mixture of seminal fluid in the way the medical men teach (Exercise the thirty-second). After quoting Aristotle's opinion that the chick is formed out of menstrual blood coagulated by the influence of the cock, he says (Exercise the twenty-first) : " The business in the generation of an egg is very different from this; for neither does the semen or rather the 'genitura' proceeding from the male in the act of intercourse, enter the uterus in any way, nor has the hen after she conceives any particle of excremeutitious matter, even of the purest kind, or any blood in her uterus which might be fashioned or perfected by the discharge of the male. Neither are the parts of the egg produced by any kind of coagulation ; neither is there anything like curdled milk to be discovered iu the uterus. The cock, I say, contributes neither form nor


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matter to the egg, but that only by which it becomes fertile and fit to engender a chick. And this faculty the cock confers by his semen (genitura) emitted in the act of intercourse, not only on the egg which is already begun, but on the uterus and ovary and even on the body of the fowl herself, in such wise that eggs which have yet to be produced, eggs, none of the matter of which yet exists either in the ovary or in any other part of the body, are thence produced possessed of fecundity." "Inflammable material is not set on fire by the contact of flame more quickly than is the hen made pregnant by intercourse with the cock" (315).

Careful observation on the fowl, the deer, the dog, the rabbit, and on many other animals, jiroves that none of them are generated out of excrement or decomposing matter. There is no basis in nature for Aristotle's opinion or that of the medical men, and all these teachings break down when brought to the test of actual observation. It is no small thing to prove the error of the belief, which had been current for two thousand years, and is even now embodied, through a quotation from St. Paul, in our burial service, that all forms of reproduction find their type in generation from dead putrescent matter. This Harvey accomplished by methods which are rigorously scientific ; and with this accurate but very imperfect knowledge he boldly faced and tried to answer the question, what is it which the cock contributes in virtue of which the egg "becomes fertile and fit to engender a chick '"?

He undertakes "to seek the truth regarding the following difficult questions : Which and what principle is it whence motion and generation proceed':' By what virtue does the semeuact":' What is it that renders the semen itself fruitful? Whether is that which in the egg is canse, artificer and principle of generation and of all the vital and vegetative operations — conservation, nutrition, growth — innate or superadded ? and whether does it inhere primarily, of itself, and as a kind of nature, or intervene by accident, as the physician in curing disease? Whether is that which transfers the egg into a jiullet inherent or acquii-ed, or is it already conceived in the ovary, and does it nourish, augment, and perfect the egg there ? What is it besides that pireserves the egg sweet after it is laid ? What is it that renders an egg fruitful ?" (374).

" In truth, there is no proposition more magnificent to investigate or more useful to ascertain than this : How are all things formed by an ' univocal agent ' ? How does the like ever generate the like? . . . Why may not the thoughts, opinions, and manners now prevalent, many years hence return again, after an intermediate period of neglect? " (583).

As we find the embryologists of the present day vexing themselves over the question, " AVhether is that which transfers the egg into a pullet inherent or acquired?" we need not wonder if Harvey's success in the investigation of this magnificent proposition seems small to us. At least we must follow him in order to understand his dictum.

As a starting-point this much seems to be certain. "The egg, even when contained in the ovary, does not live by the vitality of the mother, but is like the youth who comes of age, made independent even from its first apj)earauce; as the acorn taken from the oak, and the seeds of jjlants in general are no longer to be considered parts of the tree or herb that supported


them, but things made in their own right, and which already enjoy life in virtue of a proper and inherent vegetative power" (375).

Furthermore, "although some animals . . . are produced from females alone" (386); "it is manifest that a fruitful [hen's] egg cannot be jjroduced without the concurrence of a cock and a hen ; without the hen no egg can be formed ; without the cock it cannot become fruitful. But this view is opposed to the opinion of those who derive the origin of animals from the slime of the ground " (384).

" The egg is the terminus from which all fowls, male and female, have sprung, and to which all their lives tend — it is the result which nature has proposed to herself in their being" (371).

"And this is the round that makes the race of the common fowl eternal; now pullet, now egg, the series is continued in perpetuity; from frail and perishing individuals an immortal species is engendered" (385).

" We cannot conceive an egg without the concurrence of a male and female fowl any more than we can conceive fruit to be produced without a tree. We therefore see individuals, males as well as females, existingr for the sake of preparing eggs, that the species may be perennial though their authors pass away. And it is indeed obvious that the parents are no longer youthful or beautiful, or lusty, and fitted to enjoy life, than while they jDOSsess the power of jiroducing and fecundating eggs, and by the medium of these, of engendering their like. But when they have accomplished this grand purpose of nature, they have already attained to the height, the dxnrj of their being ; the final end of their existence has been accouij)lished ; after this, effete and useless, they begin to wither, and, as if cast off and forsaken of nature and the Deity, they grow old, aud, a-weary of their lives, they hasten to the end. How different the males when they make themselves up for intercourse, aud swelling with desire are excited by venereal impulse! It is surprising to see with what passion they are inflamed, and then how trimly they are feathered, how vainglorious they show themselves, how proud of their strength, aud how pugnacious they prove. But the grand business of life accomplished, how suddenly, and with failing strength and pristine fervor quenched, do they take iu their swelling sails, and from late pugnacity, grow timid and desponding. Even during the season of jocund masking in Yeuus's domains, male animals in general are dejiressed by intercourse, aud become submissive and pusillanimous, as if reminded that in imparting life to others they were contributing to their own destruction. The cock alone, replete with spirit and fecundity, still shows himself alert aud gay, clapping his wings and ci'owiug triumphantly he sings the nuptial song at each of his espousals; yet even he after some length of timeiu Veuus's service, begins to fail; like the veteran soldier, he by and by craves discharge from active duty, and the hen, too, like the tree that is past bearing, becomes effete, aud is finally exhausted."

Having come to the end of his means of observation, Harvey turns to reflection, the second resource of the man of science, to see how this may help him to discover how "from frail and perishing individuals an immortal species is engen


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dered." As liis studies seemed to prove that the contagion which remains in the female "after intercourse, as the efficient of the future offspring, is not of the nature of any corporeal substance," he was unable to escape the admission that it is "incorporeal." Thus driven to the wall, if he had taken refuge in "soul " or "spirit," no one could greatly blame him, for spiritual agents had been the resource of philosophers for many ages before his time. He was a true soldier of science, however, seeing as clearly as we do that this venerable formula can do notliing to help us, and preferring outspoken ignorance to this antiquated and threadbare cloak for intellectual poverty.

" If on further inquiry it should appear that it [the efficient] is neither spirit nor demon, nor soul, nor any part of a soul, as I believe can be proved by various arguments and experiments, what remains, since I am unable myself to conjecture anything beside . . . but to confess myself at a standstill ? "

What does the modern man of science in such a case? Does he not search through the whole province of knowledge to see if perchance he may find some other natural phenomenon which bears some resemblance to the subject of his studies ? Harvey says he knows well " that some censorious persons will laugh at this . . . Yet this that I do is the practice of philosophers, who when they cannot clearly comprehend how a thing really is brought to pass, devise some mode for it in accordance with the other works of nature, and as near as possible to what is true."

" Since, tlien, nothing can be apprehended by the senses in the uterus after coition, and since it is necessary that there be something to render the female fruitful, and as this is probably not material, it remains for us to take refuge in a mere conception."

Men of science in all ages, from Aristotle to Tyndall, have believed in the virtues of the provisional hypothesis; and, armed by eminent authority, Harvey undertakes, by comparing a "mere conception" with other things in nature, to frame a provisional hypothesis of generation; but natural science seems to be an uncongenial soil for the nurture of such attempts, and if time has shown that Harvey's hypothesis has little value, he errs in good company, and he also takes pains to say he does not wish it "to be taken as if I thought it a voice from an oracle," although he does hope it may "stir up the intellects of the studious to search more deeply into so obscure a subject."

Starting with the belief that "the semen of the male does not so much as reach the cavity of the uterus . . . and that it carries with it a fecundating power by a kind of contagious property " from which the female "seems to receive influence and to become fecundated without the co-operation of any sensible corporeal agent, in the same way as iron touched by the magnet is endowed with its powers and can attract other iron to itself," he holds that "when this virtue is once received the woman exercises a plastic power and produces a being after her own image."

" Yet it is a matter of wonder where this faculty abides after intercourse is completed. ... To what is the active power of the male committed ? . . . Does the woman conceive in the womb as we see by the eye and think by the brain?" " Since there are no manifest signs of conception before the


uterus begins to relax . . . and since the substance of the uterus, when ready to conceive, is very like the structure of the brain, why should we not suppose that the function of both is similar, and that there is excited by coitus within the uterus a something identical with or at least analogous to an imagination or a desire in the brain, whence comes the generation or procreation of the ovum ?" "For the functions of both are termed conceptions, and both, although the primary source of every action throughout the body, are immaterial, the one of natural or organic, the other of animal action . . . Just as a desire arises as a conception of the brain, and this conception springs from some external object of desire, so also from the male, as being the more perfect animal, and as it were the most natural object of desire, does the natural (organic) conception arise in the icterus, even as the animal concej)tiou does in the brain. From this desire, or conception, it results that the female produces au offspring like the father. For just as we, from the conception of the 'form' or 'idea' in the brain, fashion in our works a form resembling it, so in like manner the 'idea' or 'form ' of the father, existing in the uterus, generates au offspring like himself with the help of the formative faculty.

"Whoever has pondered with himself how the brain of the artist, or rather the artist by means of his brain, pictures to the life things which are not present in him, but which he has once seen ; also in what manner birds immured in cages recall to mind the spring, and chant exactly the songs they had learned the preceding summer, although meanwhile they had never practiced them; again, and this is more strange, how the bird artistically builds its nest, the copy of which it had never seen, and this not from memory or habit, but by means of an imaginative faculty, and how the spider weaves its web, without either copy or brain, solely by the help of this imaginative power ; whoever, I say, ponders these things, will not, I think, regard it as absurd or monstrous, that the woman should be impregnated by the conception of a general immaterial ' idea ' and become the artificer of generation."

"For my own part then, when I see nothing left in the uterus after intercourse, to which I can ascribe the principle of generation, any more than there is in the brain anything discoverable after sensation and experience, which are the prime sources of art, and when I find the structure of both alike, I have devised this fable."

Whatever the value of this hypothesis may be, it serves well to emphasize the fact that Harvey's opinions on generation have nothing in common with the modern discovery of the physical continuity of living matter, and it shows that his teaching that all animals come from eggs cannot possibly mean what the words now mean.

He believes the uterus conceives an animal in the same way that the brain conceives an idea; and he also tells us that he agrees with Fabricius that " the egg [of the hen] is in a certain sense an exposed uterus " (290).

Furthermore, "the hen is not the efficient cause of a perfect egg, but that she is made so in virtue of an authority, if I may use the word, or power required of the cock. For the egg, unless prolific, can with no kind of propriety be accounted perfect; it only obtains perfection from the male, or rather


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from the female, as it were upon precept from the male, as if the hen received the art and reason, the form and laws of the future embryo from his addresses" (290). Ho much for the generation of the fowl. In Exercise the sixty-ninth he describes the embryo of the doe at about seven weeks, and the human embryo about the second month after conception, but, following Aristotle, he regards these embryos in their membranes, not as embryos, but as eggs without shells. " In the way above indicated do the hind and doe, affected by a kind of contagion, finally conceive and produce primordia, of the nature of eggs, or the seeds of plants, or the fruit of trees, although for a whole month and more they had exhibited nothing in the uterus."

In this sense, then, he holds that viviparous animals are generated from eggs. He therefore maintains (as contrasted with Fabricius, who held that the greater number of animals are produced from ova) "that all animals, even the vivipara, and man himself not excepted, are produced from ova; that the first conception, from which the foetus proceeds in all, is an ovum of one description or another, as well as the seed of all kinds of plants. Empedocles therefore spoke not improperly of the ' egg-bearing race of trees.' The history of the egg is therefore of the widest scope, as it illustrates generation of every description. . . . Fabricius has these additional words: "The foetus of animals is engendered in one case from an ovum, in another from the seminal fluid, in a third from putrefaction ; whence some creatures are oviparous, some


viviparous, and yet others born of putrefaction or by the spontaneous act of nature, automatically."

" Such a division as this, however, does not satisfy me, inasmuch as all animals whatsoever may be said in a certain sense to spring from ova, and in another sense from seminal fluid, and they are entitled oviparous, viviparous or vermiparous rather in resjoect of their mode of bringing forth than of their first formation."

We see then that, unfamiliar as his words often seem, and while he holds that the organizing influence which produces the chick from the egg is a "divine mystery," we owe to Harvey the demonstration and clear formulation of the following truths :

There is no basis for the venerable doctrine that the higher animals are generated from excrement.

The hen's egg, even before it leaves the ovary, is an independent orgauism, which enjoys life by its own right, and perfects itself by nutrition.

The embryo assimilates homogeneous food, and by means of an inherent organizing power converts it into the structure of the living animal Nutrition, growth and development go on together, and the embryo arises by epigenesis or differentiation.

Many animals which have been held to arise from putrescent slime actually come from microscopic eggs.

"Animals are entitled viviparous or oviparous or vermiparous rather in respect of their mode of bringing forth than of their first formation."


LONG, THE DISCOVERER OF ANESTHESIA.

A PRESENTATION OF HIS ORIGINAL DOCUMENTS.

By Hugh II. Young, A. M., M. D., Assistant Besident Siirgeon, Johns Hopkins Hospital, Baltimore.

[Being in substance a paper read before the Johns Hopkins Hospital Historical Society, Xorember 8, 1890, with additions.]


It was my good fortune last summer to meet Mrs. Fanny Long Taylor, whose father, Dr. Crawford W. Long, is thought by many to be the original discoverer of anesthesia.

As she put me in possession of her father's papers, I thought they might prove sufficiently interesting to warrant their presentation to this Society.

During the famous ether controversy which was waged in the forties and fifties the work of Long received little attention. A modest, retiring man, who abhorred public strife and controversy, too honorable to wish pecuniary reward for his discovery, it is not strange that he made no effort to get the reward from Congress, but preferred to let the justice of his claim be judged by an unbiased posterity.

Crawford W. Long was born in Danielsville, Ga., on the first of November, 1815. His grandfather was Capt. Samuel Long of Pennsylvania, who made a brilliant record in the Revolutionary war and was one of Lafayette's captains at Yorktown. Soon after the close of that eventful struggle he left his native State and took his family to Georgia, where they settled along with a large colony of Peunsylvanians. His son, James Long, received every educational advantage


there obtainable, and inheriting his father's executive ability, became one of the prominent men of his State. Although engaged in mercantile pursuits he was a hard student of the law, and so well versed in the principles of jurisprudence that he was often consulted by judges in difficult cases.

He represented his people in the Senate for a number of years and was the intimate friend, adviser and confidant of Wm. H. Crawford, Georgia's greatest statesman, at different times Secretary of State, minister to France and candidate for the Vice-Presidency. As an evidence of attachment he gave his eldest son the name of Crawford. Coming from such ancestry it is not wonderful that young Crawford early showed promise of rare ability. As a boy he was studious and mature beyond his years, and entered Franklin College at so early an age that he was known as " baby." Notwithstanding this fact he graduated as Master of Arts second in his class at the age of nineteen. Alexander II. Stephens was his room-mate, and so much older that he was dubbed "daddy" by the college boys. Though pursuing different paths, Stephens and Long kept up an inti.nate friendship all their lives. After studying under a preceptor for one year


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Long graduated at the University of Pennsylvania in 1839. While there he was recognized as a man of marked ability and fond of experimental work.

After graduation he spent one year in a New York hospital, where, it is said, he made such a reputation for himself as a surgeon that he was urged to apply for the position of surgeon in the U. S. Navy. Obedient to his father's wishes, however, he returned to practice in his native State and located in Jefferson, .Jackson Uo., Georgia, in 1841, at that time a small country town, far removed from any railroad, in the midst of a farming community whose only factory was the cotton gin.

Here Dr. Long soon acquired an extensive and lucrative practice, and although young was noted for his quiet, dignified bearing, which endeared him to all. His office was a favorite meeting-place for the young men of the town, who would often gather there to pass a merry evening together.

About this time it became fashionable to inhale laughinggas for its exhilarating effects. Itinerant lecturers on chemistry would conclude an evening's entertainment with a nitrous-oxide party in which the participants would get gloriously drunk from its inspiration.

The practice spread throughout the country, and at -Jefferson during the early part of the winter of '41 a coterie of young friends begged Dr. Long to let them indulge in the far-famed luxury.

Dr. Long replied that he had uo means of preparing nitrousoxide gas, but that sulphuric ether would produce similar exhilaration. The company being anxious to try it, the ether was produced, all inhaled of it and soon became hilarious.

The young men were delighted and hastened to tell their friends of Dr. Long's wonderful drug, and thus the inhalation of ether for sport soon became very popular over that section of Georgia, and almost every party ended up with an " ether frolic," as it was called.

During January, 1842, the ether frolics at Dr. Ijong's office became very frequent and were well attended, and some of the young men probably became pretty thoroughly intoxicated, as Dr. Long discovered that he and others would afterward have considerable bruises about their persons of which they had no knowledge.

Being a thoughtful man, he at once remarked thai ether must have the poiver of rendering one insensibU to pain, and therefore available for prevent itig pain in stirgical operations.

This was January, 1842, and Dr. Long at once determined to prove his discovery on the tirst surgical case_ he should have. That opportunity came on March 30th, when Long administered ether to Mr. James M. Venable till completely anaesthetized, and then excised a small cystic tumor from the back of his neck. Imagine the surprise of the patient when on regaining consciousness he was told that the operation was over, and his amazement when he saw the tumor in the hands of the surgeon and he had not felt a scratch. This was four and one-half years before Morton's earliest claims.

An original paper read by Dr. Long before the Georgia State Medical Society in 1852, describing these events in his own words, is appended to this paper — see Appendix I.

It is worthy of note that two and a half years later Wells of Hartford discovered the ansesthetic powers of nitrous oxide


under very similar circumstances. He attended an entertainment given by a popular lecturer on chemistry, inhaled nitrous oxide for its exhilaration, and saw a man under its influence injure his ankle severely without being conscious of it. From this he concluded that nitrous oxide was capable of producing anesthesia and proved it in extracting a tooth.

Morton, on the other hand, got his suggestion as to the ansEsthetic power of ether from Jackson, who, after using ether to relieve the pain and dyspnoea following the accidental inhalation of chlorine gas — an antidote well known in chemistry then — inferred that it might be useful as an anajsthetic. Jackson did not test the correctness of this observation, which he claims to have made about the same time that Long etherized his first case, but left it for Morton to prove practically four and a half years later.

Dr. liOng reports the first five cases in which he used ether, being desirous only of establishing priority of use. An examination of the letters and certificates before me, however, shows that he must have operated on at least eight cases before ^Morton's "discovery." This number seems small, but is not so astonishing when we remember that the country was sparsely settled, that Jefferson was a mere village, and Long had just entered practice.

I will now read in substantiation of these statements a copy of the original account in Dr. Long's journal against Mr. Venable for medical services rendered, certified to by a clerk of the Superior Court.

"James Venable

To Dr. C. W. Long, Dr. 1842. cts.

January 28th, sulphuric ether, .25

March 30th, sulphuric ether and exsecting tumor, 2.00 May 13th, sul. ether, .25

June 6th, exsecting tumor, 2.00

Georgia, I

Jackson County. ' I, P. F. Hinton, clerk of the superior court of said county, do certify that the above account is a correct copy of an original entry made in his book for medical services for the year 1842. Given under my name and seal of office this 27th of March, 1854. [Seal] (Signed) V. ¥. Hitfms, Vlerl.- S."

The following paper relative to the fashion of inhaling ether for its exhilarating effects is interesting as showing how the custom in Georgia started with Dr. Long :

" I certify that on the first of January, 1842, I resided in .Jefferson, Jackson Co., Georgia, and that about that time myself with several other young men were in the habit of meeting at Doct. C. W. Long's shop, and other rooms in the village, and inhaling ether which he adminutered to us.

On the 20th of January of the same year I removed to Athens, where I introduced the inhalation of ether. I and several of my young associates frequently assembled ourselves together and took it for the excitement it produced. After that I know it became very common to inhale ether in Athens, and tbat it was frequently taken in the college campus and on the street.

(Signed) R. H. Goodman,

August 4th, 1849. Athens, Georgia."

When we see daily the dreadful distaste patients who have been etherized have for ether, it seems strange that any one could become fond of its use.


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I will now read an account of the first operation as given by Mr. James M. Venable:

"I, James M. Venable, of the county of Cobb and State of Georgia, on oath depose and say, that in the year 1842 I resided at my mother's in Jaclcson County, about two miles from the village of Jefferson, and attended the village academy that year.

In the early part of the year the young men of Jefferson and the country adjoining were in the habit of inhaling ether for its exhilarating powers, and I inhaled it frequently for that purpose, and was very fond of its use.

While attending the academy I was frequently in the office of Dr. C. W. Long, and having two tumors on the back of my neck, I several times spoke to him about the propriety of cutting them out, but postponed the operation from time to time. On one occasion we had some conversation about the probability that the tumors might be cut out while I was under the influence of s. ether, without my experiencing pain, and he proposed operating on me while under its influence.

I agreed to have one tumor cut out and had the operation performed that evening after school was dismissed. This was in the early part of the spring of 1842.

I commenced inhaling the ether before the operation was commenced and continued it until the operation was over. I did not feel the slightest pain from the operation and could not believe the tumor was removed until it was shown to me.

A month or two after this time Dr. C. W. Long cut out the other tumor, situated on the same side of my neck. In this operation I did not feel the least pain until the last cut was made, when I felt a little pain. In this operation I stopped inhaling the ether before the operation was finished.

I inhaled the ether, in both cases, from a towel, which was the common method of taking it. Georgia, -v (Signed) James M. Ven.\blk.

Cobb Co., > Sworn to before me.

July 23rd, 1849. J Alfred Manes, J. P."

This operation was clone in the presence of fonr witnesses, Jas. E. Hayes, A. T. Thurmond, W. H. Thurmond, principal of the academy, and Edmund S. Rawls, the last of whom testifies as follows :

"Georgia, -i I, Edmund S. Rawls, of Rome, Floyd Co., Ga., on Clarke Co. J oath depose and say that ... on one occasion during that year (1842) I was present with James M. Venable in the office of Dr. C. W. Long in Jefferson, Jackson Co., Ga., and witnessed Dr. C. W. Long cut out a tumor from the side of neck of J. M. Venable while said Venable was fully under the effects of the vapor of s. ether inhaled from a towel, and without his exhibiting the least symptoms of suffering pain from the operation. J. M. Venable was so unconscious of the operation having been performed that he would not believe the tumor was removed until it was shown him. (Signed) E. S. Rawls.

Sworn to and subscribed before me this 2nd November, 1853.

E. L. Newton, /. J. C."

The patient continued to inhale ether until the operation was over, was entirely unconscious of its performance, and felt no pain. Surely this was complete ansEsthesia. This fact has been denied by Dr. Wm. J. Morton, son of the Boston discoverer, who says it was no more than mere exhilaration.

It has been stated that Long kept his discovery secret and that he therefore deserved no credit for it. I present certificates from Drs. Laperriere and Carlton, which show that his work was well known to citizens of the town of Jefferson and neighboring cities, particularly Athens, which was then the


centre of learning and culture in Georgia; that it was considered a remarkable discovery by the populace, and that the prominent physicians knew of it and realized its importance. See Appendix II.

Dr. Carlton was then a student under Dr. Moore. One year later (1844) he used ether in extracting a tooth. This was probably the first use of ether in extracting teeth. Dr. James Camak, another student of Moore, was present and assisted in the same operation and corroborates Carlton's statements.

Can Dr. Long be blamed for not publishing at once a report of his first case or two when they were well known to the physicians of that part of the State ? He had no Massachusetts General Hospital at his back, and he knew that such startling claims coming from one so young (he had not been practicing one year) would be severely criticised. It is but natural that he should be satisfied for the time being with the local and State publicity which was given to his great discovery, and waited until he could make a comprehensive report embracing all kinds of cases, such as every careful investigator does to-day.

But he kept on with his work, ojierating on two more cases under ether in 1842, and about three more during the next year, for most of which I find sworn certificates.

I have a letter from his first student. Dr. J. F. Groves, which is of particular interest as giving an insight into the character of Dr. Long and his work at that time. It is quite lengthy and I omit portions of it. The letter is written to Mrs. Taylor, Dr. Long's eldest daughter. See Appendix TIL

This letter shows conclusively that Dr. Long was thoroughly convinced of the anesthetic powers of ether, but was anxious to put it to a severe test in capital surgery. He withheld his cases of minor surgery because he wished to determine accurately the limitations and possibilities of ether.

In his paper Dr. Long does not give the details of the etherization with the minuteness we should desire. For instance, he does not say who gave the ether, the patient or himself, and he does not explain whether the patient was entirely unconscious or not, but simply remarks that he suffered no pain and did not know the tumor had been removed.

These omissions of Dr. Long led Dr. Wm. J. Morton, of New York, to write a forty-eight-page article in the Virginia j\Iedical Monthly, March, 1880, in which by dexterously quibbling with Long's innocent statements he arrives at the conclusion by a skilful process of deduction, that Long never did anything. I will read parts of this article :

"The Invention of An.esthetic Inhalation.

  • * * But we will proceed slowly. We must know who is giving the ether. Of the first operation Venable deposes under oath,

'I commenced inhaling the vapor before the ojieration was commenced and continued it until the operation was over.'

Tlius Venable kept his eye on the whole affair, knew just what was going on, otherwise how could he knowand swear to it thatbe continued the inhalation until the operation was over. Surely Veiiahlc administered the ether to himself and remained conscious all the time."

This is erroneous, for according to good legal authority


August-September, 1897


JOHNS HOPKINS HOSPITAL BULLETIN.


177


such a statement as Veiiable's could be made fi-um a knowledge based on satisfactory hearsaj' evidence and would be accepted in law.

But he goe.s on : "But now comes the damnatory point of this second experiment. The patient felt pain. Tliis both Long and Venable confess. Here tlien is positive failure ; Dr. Long's ansesthetic state was nothing more nor less tiian the fleeting peripheral numbness often associated with the first or e.Khilaratmg stage of the complete anesthesia of to-day. But why did Dr. Long not take the towel into his own hand and force the ether? Why not make his patient insensible to pain if he knew tliis could be done?

" Knowing what medicine knows to-day, how wonderful this halting of Long — tliis pause at a most critical moment — on the very threshold of discovery! So nicely balanced is the situation thiit it almost seems as if he would topple over into discovery; but he falls the other way.

" It seems almost inexplicable that he did not seize the towel, force the anaesthesia to the stage of stupor, perform the operation, and proclaim the discovery to the worUi," —

and we might add, patent it at once I

It is a fact well known to all surgeons that a patient may be entirely unconscious and still retain sensibility to pain. This is evidenced by the flinching before the knife when in this state. He may give evidence of feeling pain, but have no recollection of it afterward. All witnesses agree that Tenable gave no evidence of feeling pain in the first operation. He must have been jjretty thocoughly anffisthetiiied. The second operation was merely a test case to determine the length of the anaesthetic state, aud although the ether was discontinued from the beginning of the operation (which Long says was tolerably difficult on account of adhesions), still the anajsthetic state lasted until the last cut was made. We would consider .such a patient pretty thoroughly anaesthetized in Baltimore.

I have recently tested a number of patients who were being anaesthetized and found invariably that consciousness was lost before sensibility to pain — as evinced by movement of a member when pricked with a pin.

It was therefore practically certain that no j)erson could administer ether to himself, an act requiring consciousness — aud become sufficiently anaesthetized for even very small operations; but in order to settle the question definitely I determined to administer ether to myself, using the same methods as were employed by Long in 1842.

Accordingly, under the direction of Dr. F. II. Hagner of Washington, I placed a folded towel over my face and poured



Dr. CRAWFORD W. LONG


ether upon it from time to time at his bidding, as long as 1 was conscious. During this time Dr. Hagner pricked me with pins up to the last application that I remember. Toward the last the pin pricks did not produce the usual sensation of pain, but a peculiar disagreeable clanging sound in the ear.

Dr. Hagner thus briefly describes the experiment: "Dr. Young jjoured ether on the towel when so instructed by me. After a number of such additions the movements of his arm became very unsteady and he would spill some of the ether on his neck. Soon after the last application, made at my request, I pricked him with a pin and he moved his leg. I then instructed him several times to add more, but he made no attempt to do so and seemed unconscious. I then pricked him with pins several times, but received no response for about a minute, when he again responded to a prick of pin and suddenly became conscious. Comjilete consciousness returned almost immediately.

" I feel certain that he lost consciousness before sensibility to pain, and that if I had attempted to do the smallest surgical operation he would have been conscious of pain before its completion."

It is therefore certain that Yenable would have been conscious long before the small tumor was removed and would have suffered considerable pain, if he had conducted his own etherization. Nor is it probable that Long intended to convey that idea. We might with propriety say to-day that our patients "inhale ether until anesthetized," if we did not care to specify the details of etherization. Hut in a document quoted above R. H. Goodman says, in speaking of the ether frolics, " We were in the habit of meeting at Dr. Long's shop and inhaling ether which he administered to vs." It seems probable therefore that some one administered ether to the persons on whom he operated, too.

Desirous of settling these trivial points on which Morton would have Long deprived of every honor, I addressed a letter a few days ago to Long's first student. Dr. J. F. Groves, w'hose document I have quoted above. I saw that he would now be about 75 years of age and waited for an answer with considerable au.xiety. To my surprise and delight I received a letter from him yesterday which supplies all of Dr. Long's omissions. Dr. Groves did not see the first operations, as he did not enter Dr. Long's office till 18W, but soon after his entrance he assisted in the operation on the negro boy in which two fingers were amputated, early in 18-t5, aud at my request he describes this etherization in detail.


178


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 77-78.


As this case occurred a year ami a half before Morton's discovery, it is equally good as the first for my purposes. It is as follows :

A Recent Letter fkom Long's First Student.

"CoHUTTA, Ga., Jan. 15th, 1897. Dr. Hugh H. Young,

Dear Sir ; * * * The patient was placed in a recumbent position, on a bed, with hand to be operated on to the front for convenience to tlie surgeon. Dr. Long poured etiier on a towel and held it to the patient's nose and mouth, too, to get the benefit of inhalation from both sources. Dr. Long determined when the patient was sufficiently etherized to begin the operation by pinching or pricking him with a pin. Believing that no liarm would come of its use for a reasonable length of time he profoundly anesthetized the patient, then gave me the towel and I kept up the influence by holding it still to the patient's nose. The patient was entirely unconscious — no struggling — patient passive in the hands of operator. After a lapse of lifty years you would hardly suppose that a man could remember every minute detail, but I have clearly in mind all the facts I have given you.

Your ob't servant,

(Signed J J. F. Groves, M. D."

Long then administered ether as it is done to-day. He did not pause at the threshold of discovery or topple the other way, but kept right ahead and by careful observation, experimentation and reflection discovered that ether was a safe, sure and complete anajsthetic.

Nor did his patients etherize themselves and at the same time superintend the operation, as Dr. Morton would have us believe.

As quoted above, Morton grasps eagerly at the acknowledgment of pain at the end of the second operation, where the ether had been discontinued, and from tnat isolated instance characterizes all of Dr. Long's cases as failures. But in his eagerness to annihilate Dr. Long he seems to have overlooked the fact that in the first report of anassthesia with Morton's " Letheou " at the Massachusetts General in 1846, Dr. Bigelow* says, in speaking of the first operation, "During the operation the patient muttered as in a semi-unconscious state, and afterwards stated that the pain was considerable," and in the second, " The operation lasted four or five minutes, during which time the patient betrayed occasional marks of uneasiness." But these certainly were not failures, although the ausesthesia was not as complete as in Dr. Long's previous cases.

Li his paper Long speaks of "those high in authority who were advocating the mesmeric state as adequate to prevent pain in surgical operations." Contemporary medical literature furnishes ample verification of these statements, according to Dr. Grandy,t who says :

" The journals were full of discussions upon the phenomena of mesmerism, animal magnetism, etc., and wonderful reports were coming from European hospitals of operations done without pain during the ' magnetic sleep.'

"Jules Gloquet had excised a cancerous breast with the axillary glands and the patient showed no sign of pain. Top


  • Boston Medical and Surgical Journal, Nov. 1846.

t Va. Med. Monthly, Oct. 1893.


ham of London, in 1843, had amputated a thigh, and Dr. Diigas of Augusta, Georgia, in 184.5, twice extirpated the mamma of a female under the mesmeric sleep.

"We can imagine what efEect these cases had on the mind of Long. Need we wonder therefore that he was the more particular in his experiments on etherization. Such were the reasons for his silence, and while the sequel was unfortunate, his course was cautious and commendable."

While thus waiting, his opportunity was lost. A second discovery was made in Boston in 1846, was published immediately, and anesthesia became the property of the world.

Friends of the other " discoverers " have often stated that as Long made no publication of his work he deserved no credit for it. To this Dr. J. Marion Sims responds very forcibly as follows:*

" Now upon this point Long, Wells, Morton and Jackson stand individually upon the same level.

Long exhibited to medical men and to the community his operations under ether in 1842. Wells exhibited to medical men and to the community his operations of the extraction of teeth under nitrous oxide gas in 1844. Morton exhibited to medical men and the community the use of his secret remedy "Letheon," 1846, as an anesthetic. But Morton was fortunate in showing his patent remedy to the great surgeons of Boston, and it was not Morton, but it was Warren and Ilayward and Bigelow who performed the operations to which the world owes the immediate and universal use of anfesthesia in surgery. If Morton could have had his w,iy he would have deodorized the ether and kept it secret from the world. Neither Wells nor Morton nor Jackson ever published a word on the subject till it burst forth in a blaze from the labors of the hospital surgeons already named. When Warren and Hay ward and Bigelow proved the real greatness of the discovery [and published it broadcast], then it was that Wells, Morton and Jackson began the war of pamjihlets, and not till then did either of them publish in any scientific journal a line about ana'sthesia."

The Famous Ether Controversy.

In 1849 Morton petitioned Congress for a reward for his discovery. He was at once opposed by Jackson and the friends of Wells, who was then dead. The celebrated ether controversy, thus begun, occupied the attention of Congress for many years, and was characterized by the greatest animosity between these former bosom friends and companions.

For five years Long i-efused to take part in the conflict, but finally in 1854, persuaded by his friends that in that way alone could he obtain recognition of his claims, he wrote to Senator Dawson giving an account of his work. It seems that Dawson was a friend of Jackson, for he wrote to him of this new claimant and requested him to investigate his case. This .Jackson did, calling upon Long at his home in Athens on March 8th, 1854.

The Ixtekview betweej^ Loxa .vxd Jacksox. At this interview lion. C. W. Andrews, a prominent justice.


  • Va. Med. :\ronthly, :\Iay, 187


August-September, 1807.]


JOHNS HOPKINS HOSPITAL BULLETIN.


179


was present, and certifies that after satisfying himself of the genuineness of the claims, Jackson proposed to Long to lay their claims conjointly before Congress — he, Jackson, to claim the discovery, and Long to claim the first practical use, — his object evidently being to get ahead of Morton.

This proposition Dr. Long rejected, being satisfied that he was entitled to both. In a letter to Hon. D. L. Swain, ex-governor of North Carolina, which I have here, he says in regard to this transaction: "The only ground Dr. Jackson urged for his right to the discovery was that while suffering with pain and dyspncea, in February, 1842, from breathing chlorine gas, he inhaled ether and found that while under its influence he was free from pain. He does not claim that he suggested its use to jjrevent pain in surgical operations until more than one year after my first operation was performed. I cannot give the exact date when I was first led to believe that ether would prevent pain in surgical operations, but I know it was as early as February, 1S42."

Now in 1839 Pereira, in his "Elements of Materia Medica," states : " The vapor of ether is inhaled to relieve the effects caused by accidental inhalation of chlorine gas. If the air be too strongly impregnated with ether, stujjefactiou ensues."

So there was very little new in Dr. Jackson's " discovery," and a mere untried inference hardly deserves the title of discovery.

Dr. Jackson finally acknowledged the justice of Dr. Long's claims and wrote to Senator Dawson to that effect.

On April 15th, 185-t, the appropriation bill was up before the Senate for its final reading. The friends of Wells and Morton, relying on the volumes of manuscript they had presented, were confidently awaiting the result, when Senator Dawson arose and said that he had a letter from Dr. Jackson which acknowledged that a Dr. Long in Georgia had undoubtedly used ether before any of the claimants for the appropriation.

Coming as it did from so prominent a contestant, this announcement fell like a thunderbolt on the rival claimants, and from that time they seem to have lost all Iwpe of gaining the reward and passively allowed the bill to die.

Desirous only of preventing another from being recognized by Congress as the discoverer, and not wishing any pecuniary reward himself, Long never pushed the matter farther, and his documents of proof were never even brought uj) before Congress.

I have here an interesting memento of that conference between the two discoverers, in a card on which Jackson has written a note to Long. On one side it reads :

"For Dr. C. W.Long,

of Athens, (Ja. C. T. Jackson,

New York Hotel, (over) " and on the reverse :

"Telegraph from J. L. Hayes, Washington. 'Assignee struck out by request of Mr. Everett.' Bill probably will come up in House July next."

Edward Everett was then senator from Massachusetts. In


the transactions of the Senate, April 19th, 1854, I find the following explanation of the bill by Senator AValker:

" The bill as amen. led recites that a discovery of anaesthesia has Ijeen made — that it is believed the discovery was made by some one of the following persons, W. T. G. Morton, Chas. T. Jackson and Horace Wells, but it does not appear to the satisfaction of Congress which of those parties was the original, true and first discoverer thereof. It proposes to ap|>ropriato $100,0(0.00 as a recompense for the real discoverer. In order to determine this it shall bo the duty of the district attorney of the United States for the Northern District of New York, to file in the circuit court of the United States for that district a bill of interpleader wherein reciting the act or its substance, the Secretary of tlie Treasury shall be complainant, and AV. T. G. Jlorton, Chas. T. Jackson and the personal representatives of Horace Wells or any other person who may make application to thecourt for that purpose shall be defendants. The issue is to be which of the parties named was the original, true and first discoverer of anseathesia, and the court is to decide which one that is and direst that the sum of $100,000 he paid over to him."

At the instance of Senator Dawson Dr. Long's name was also inserted in the bill.

I have carefully searched the Congressional Eecords and find that this bill never came up before the House for final passage, and conseqixently never reached the district court of New York. It seems to have been abandoned.

Several years later Dr. Jackson wrote an article in the Boston Medical and Surgical Journal giving Long the credit for the first use of ether in surgery. I have here Dr. Long's copy of that journal. The communication is so imjiortant that I will read most of it :

" The Boston Medical and Surgical Journal.

Boston, Thursday, Apr. 11, ]8()1.

First Peactical Use of Ether in Surgical Operations.

Messrs. Editors: — At the request of the Hon. Mr. Dawson, U. S. Senator from Georgia, on March Sth, 1854, 1 called upon Dr. C. W. Long, of Athens, Georgia, while on my way to the Dahlonega gold mines, and examined Dr. Long's evidence, on which his claims to the first practical operations with ether in surgery were founded, and wrote, as requested, to Mr. Dawson, who was then in the U. S. Senate, all I learned on the subiect. From the documents shown me by Dr. Long, it appears that he employed sulphuric ether as an anaesthetic agent :

1st, March 30th, 1812, when he extirpated a small glandular tumor from the neck of James M. Venable, a boy in Jefferson, Georgia, now dead.

2nd, July 3rd, 1842, in the amputation of the toe of a negro boy lielonging to Jlrs. Hemphill, of Jackson, Ga.

3rd, Sep. 9th, 1843, in extirpation of a tumor from the head of Mary Vincent, of JacKson, Ga.

4th, Jan. Sth, 1845, in the amputation of a finger of a negro boy belonging to Ralph Bailey, of Jackson, Ga.

Copies of the letters and depositions proving these operations with ether were all shown me by Dr. Long. * * *

I then called on Profs. Joseph and John Le Conte, then of the University of Georgia, at Athens, and inquired if they knew Dr. Long, and what his character was for truth and veracity. They both assured me that they knew him well, and that no one who knew him in that town would doubt his word, and that he was an honorable man in all respects.

Subsequently, on revisiting Athens, Dr. Long showed me his folio journal, or accountbook, in which stand the following entries :


180


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 77-78.


' James Venable

March 30th, 1842, Ether and excising tumor, $2.00 May 13th, Sul. Ether, .25

June 6th, Excising tumor, 2.00'

On the upper half of the same page, several charges for ether sold to the teacher of the Jefferson Academy are recorded, which ether Dr. Long told me was used by the teacher in exhibiting its exhilarating effects, and he said the boys used it for the same purpose in the academy. I observed that all these records bore the appearance of old and original entries in the book.

On asking Dr. Long why he did not write to me or make known what he had done, he said, when he saw my dates he perceived that I made the discovery before him, and he did not suppose that anything done after that would be considered of much importance, and that he was awakened to the idea of asserting his claims to the first practical use of ether in operations, by learning that such claims were set up by others for this merit, and consequently he wrote to the Georgia delegation at Washington, stating the facts which Senator Dawson had requested me to inquire into.

I have waited expecting Dr. Long to publish his statements and evidence in full, and therefore have not before published what I learned from him. He is a very modest, retiring man and not disposed to bring his claims before any but a medical or scientific tribunal. * * *

Had he written to me in season I would have presented his claims to the Academy of Sciences of France, but he allowed his case to go by default, and the academy knew no more of his claims to the practical use of ether in surgical operations than I did.

Boston, >ipril 3, 1861. Charles T. Jackson, M. D."

The list of operations as given by Dr. Jackson is not complete, as he has omitted the second operation on Venable, and a number of the later operations. In a letter to Dr. Sims, which I have, Dr. Long denies absolutely that he ever acknowledged that Dr. .Jackson was the prior discoverer. He had been led to infer that ether had ana3sthetic powers several months before he got a chance to verify it, and before Jacksou claims to have made similar inferences, but he dated bis claims of discovery from the time of his first practical demonstration. Before that it was a mere supposition, as was Jackson's also.

But barring these inaccuracies, Dr. Jackson's paper, coming as it does from one who so zealously coveted the title of discoverer, is a remarkable admission.

The interview between Long and Jackson must have been most amicable, and Long evidently felt the greatest respect for Jackson, as shown in the following letter:

"Athkns, Ga., Nov. 15th, 1854. Dr. C. T. Jackson.

Dear Sir: — I design to prepare an article with the proofs of the priority of my claims of the discovery of the anresthetic powers of ether and of its applicability to surgical operations. I design having this published in pamphlet form for distribution among the members of the medical profession, and I expect to present such proof with the article as will satisfy all that I am entitled to all I claim.

Ours are rival claims, and permit me, sir, to say that although our claims are conflicting, I would not knowingly say anything in the article which would be displeasing to you. I entertain high respect for you as a gentleman and man of science and feel honored by your acquaintance.

Still it becomes each one of us to use all honorable means to advance his own claims, and I know you will not blame me for attending to this matter, which so much concerns my reputation.

Shall it meet with your approbation, I may refer to your admis


sions to Hon. W. C. Dawson and myself, of the belief of the correctness of my claims. I will, however, make no allusion to your letter to Mr. Dawson or to the conversation held with myself unless

it meets with your sanction

Your obedient servant, C. AV. Long."

Morton's Patent.

It has often been stated by the friends of ilorton that he never attempted to enforce his patent. This statement has lately been reiterated by his wife in McClure's Magazine. On this point the following letter from a prominent army surgeon to Long may be of interest:

" U. S. Marine Hospital,

Chelsea, Mass., April, 1859. Dr. Crawford W. Long, Athens, Ga.

Sir: — Hon. Judge Hyllier, Solicitor of Treasury Department, informed me about a year since, and recently repeated the same, that some years since you used sulph. ether as an anaesthetic and had a record of the same. If it is not asking too much of you, I would be greatly obliged if at your earliest convenience you would forward me a statement of the facts.

I take the liberty to ask this of you because Mr. W. T. G. Morton, to whom in conjunction with Dr. C. T. Jackson a patent was granted in Nov., 1846, for using ether, has brought a suit against me as a government officer for an infringement of his patent.

Judge Hyllier was confident that you could furnish me with proof sufficient to satisfy a jury that you used it way before he or Jackson claimed to have made the discovery. I should have asked for these proofs through my attorney and had them properly witnessed, etc., but the Secretary of the Treasury having decided that I used the article on my own responsibility and therefore the Govt, were not bound to defend me, I wish to save as much expense as possible. Very respectfully,

[Signed] Charles A. Davis, M. D.,

Physician and Superintendent."

In reply Long gives a detailed account of his work, and then adds : " I presume Dr. Jackson is not party to the prosecution, as I know he entertains no good feelings towards W. T. Morton. If you think proper you can see him and ascertain the character of proof I can make. From the little acquaintance formed with him I entertain a high opinion of him as a gentleman and think he will do me justice notwithstanding he himself claims to have made the discovery and has received several awards."

Dr. Davis's letter was written twelve years after Morton's " Letheon " was patented, and many years after ether was the common property of the world. It was probably Morton's last attempt to get money from the U. S. Government.

The ether controversy was never reopened and Long's work was unknown to the world until 1877, when J. Marion Sims learning of him through accident, investigated his claims, was fully convinced of their merit, and vigorously demanded their recognition by the medical profession. His paper appeared in the Virginia Medical Monthly, May, 1877.

The Wilhite Cl.\ims.

This article, which obtiviued for Long the first recognition of any consequence, was the outcome of a conversation which Sims had with a Dr. P. A. Wilhite, of Anderson, S. C. Wilhite told Sims that be had witnessed the first surgical o])eration ever done under ether, and recounted Dr. Long's


August-September, 1897.]


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181


first case, saying that lie was one of four students who were then in Dr. Long's office.

He also said that " he presumed that he was the first j)erson who ever profoundly etherized any one," and told how he was at a quilting party in which the boys and girls had concluded the evening by inhaling ether for sjiort; how they had caught a negro boy, and as he refused to inhale the ether, had firmly held a handkerchief soaked with ether over his face, when to their horror his breathing became stertorous and he could not be aroused. He then vividly pictured their alarm when they realized that they had murdered a fellow-being, and thdr determination to leave the country, which was prevented by the timely arrival of a physician who restored the boy to consciousness.

Wilhite iheu related how when the idea of using ether to prevent pain in surgical operations had occurred to Long, he had eiicoura<jed him hy relating the story of the negro boy.

Dr. Sims at once communicated with Dr. Long and soon convinced himself of the truth of his claims, but unfortunately he failed to investigate Wilhite's statements, but embodied them in full in his article, giving to Wilhite the credit of first intentionally producing profound ana;sthesia with ether.

Dr. Sims' paper was given great publicity and the Wilhite story has been accej^ted as true, and copied by many writers on the subject, most notably by Sir Jas. Paget.*

The negro boy story lacks probability, as Wilhite did not enter Long's office until 1844, two years after the first operation, as the following letter from Long to Wilhite shows :

"Athens, Ga., May 20th, 1S77. Dk. p. a. Wilhite.

Bear Sir : — I received Br. Sims' article on anaesthesia yesterday and find several mistakes. Dr. Sims states that yourself, Dr. Groves, and Drs. J. D. and H. E. J. Long were students of mine and witnessed the operation performed on Venable in 1842. Your recollection failed you at the time. As it was several years, at least two, before either entered my office, you will see that you were mistaken in giving Dr. Sims this information. You also make a mistake in saying that the first inhalation in Jefferson of ether for its exhilarating effects was before the same persons.

  • * * I wrote to Dr. Sims informing him of the errors and

asking him if he considered the mistakes of sufficient importance to be noticed, etc. (Signed) 0. W. Long."

Dr. Wilhite replied as follows :

"Anderson, S. C, June 27, '77. Dr. C W. Long.

Dear Doctor : — Yours of the 22nd inst. is at hand, and I have also just received a letter from Dr. J. M. Sims, which I will answer to-day. » » *

In my statement I did make a mistake in regard to my being present at the first or second operation, which mistake I will correct. But if you still prefer I will send a certificate. * * •

Let me know and I will give you any information or assistance in this great matter. Yours truly, etc.,

(Signed ) P. A. Wilhite."

Ill the letter to Wilhite, Long makes no comment on the negro-boy incident, but his daughter informs me that he


  • The Nineteenth Cenliiry, 1880.


repeatedly told her that he had never heard of it before it appeared in Sims' article.

It is to be regretted that the justification of Long's claims should have been linked so closely with such misstatements.

Sims sailed for Europe soon after the publication of his article, and Long died in a few months, and Wilhite's statements went unchallenged for many years.*

Among Dr. Long's papers are many more documents — affidavits of persons operated on and witnesses to them, and letters to different prominent men — but their recital would take up too much time, so I will close with a few words regarding his after life.

In 1842 Dr. Long was married to Miss Caroline Swain, a niece of Governor Swain of North Carolina, a very handsome and attractive woman, who proved a devoted wife. She survived her husband many years.

Long remained in Jefferson for ten years, when he removed to Athens and there spent the rest of his days. By inheritance and professional labors Dr. Long had amassed a fortune, which was largely swept away by the war of secession, and at its close he found himself reduced to poverty, with a large family to support.

Although he soon regained an extensive practice, the desolation of the country and the general poverty of the people made the remainder of his life a continual struggle against poverty. His life, which, up to the time of Dr. Sims' article, had been one of disappointments, after that suddenly became brighter, for from all parts of the world men prominent in the medical profession hastened to give him the credit which had so long been withheld.

His claims were never investigated by the American Medical Association, as he often desired, but many minor societies and the "Eclectic" Medical Association passed decrees in his favor, and a statue was erected in his honor in Paris, France.

But he was not long to enjoy the praise and long-delayed honors which were now heaped upon him. Within a few months, while laboring at the bedside of a delicate patient, he was stricken with apoplexy and died the next day, June 16th, 1878, at the age of sixty-two, poor in worldly goods but rich in the gratitude of his people. His oft-repeated wish to die in harness had been granted.

A strange fatality seemed to hang over the lives of all connected with the discovery of auajsthesia !

Wells, disappointed and disheartened by the rejection of his claims by the French Academy, became insane and committed suicide in 1848.

Morton gave up a very lucrative practice and vainly spent his life in trying to enforce his patent and get a reward from Congress. He died in 1868 from congestion of the brain, brought on by excitement occasioned by an article attempting to deprive him of the honor he so jealously coveted.

Long died in poverty, from apoplexy brought on by overwork in 1878.

Jackson, like Wells, became insane from the bitter contentions of his life and died in an asylum in 1880.


  • ln an article in the Virginia Medical Monthly, 1893, Dr. L. 15.

Grandy, of Atlanta, showed the error of Wilhite's statements.


182


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[Nos. 77-78.


Henri L. Stuart, founder of the Woman's Hospital, aud a great New York philanthropist, became interested in Long's claims and presented a portrait of him to tlie University of Georgia. After seeing it unveiled with great ceremony in the capitol in Atlanta, one year after Long's death, he went to Athens as a guest of the Longs, to visit the grave of the discoverer of anaesthesia. Arriving at night, he waited till morning to fulfil his heart's desire. But this was never gratified. IJuring the night he had a paralytic stroke aud died at the home of the Longs after lingering several weeks. At his own request his remains were interred next to those of Crawford Long — two great benefactors side by side.

Appendix I. Dr. Long's Original Paper.*

In the month of Dec, 1841, or Jan., 1842, the subject of the inhalation of nitrous oxide gas was introduced in a company of young men assembled at night in the village of Jefferson, Ga., and the party requested me to prepare tliem some. I informed them I had not the requisite apparatus for preparing or preserving the gas, but that I had an article (sul. ether) which would produce equally exhilarating effects and was as safe. The company were anxious to witness its effects, the ether was introduced and all present in turn inhaled. They were so. much pleased with its effects that they afterwards frequently used it and induced others to do the same, and the practice soon became quite fashionable in the county and some of the contiguous counties.

On numerous occasions I inhaled ether for its exhilarating properties, and would frequently, at some short time subsequent to its inhalation, discover bruised or painful spots on my person which I had no recollection of causing and which I felt satisfied were received while under the influence of ether. I noticed my friends while etherized received falls and blows which I believed were sufiicientto produce pain on a person not in a state of anaesthesia, and on questioning them they uniformly assured me that they did not feel the least pain from these accidents. Observing these facts I was led to believe that anesthesia was produced by the inhalation of ether, and that its use would be applicable in surgical operations.

The first patient to whom I administered ether in a surgical operation was Mr. James M. Venable, who then resided within two miles of Jefferson, and at present lives in Cobb Co., Ga. Mr. Venable consulted me on several occasions in regard to the propriety of removing two small tumors situated on the back part of his neck, but would postpone from time to time having the operation performed, from dread of pain. At length I mentioned to him the fact of my receiving bruises while under the influence of the vapor of ether without suffering, and as I knew him to be fond of and accustomed to inhale ether, I suggested to him the probability that the operations might be performed without pain, and proposed operating on him while under its influence. He consented to have one tumor removed, and the operation was performed the same evening. The ether was given to Mr. Venable on a towel, and when fully under its influence I extirpated the tumor.

It was encysted and about half an inch in diameter. The patient continued to inhale ether during the time of the operation, and when informed it was over, seemed incredulous until the tumor was shown him.

He gave no evidence of suffering during the operation, and assured me, after it was over, that he did not experience the least degree of pain from its performance. This operation was performed on the 30th ]\rarch, lSt2.


' Read liefore Georgia State Medical .Society in 18.')3.


The second I performed on a patient etherized was on the 6th June, 1812, and was on the same person, for the removal of the other small tumor. This operation required more time than the first, from the cyst of the tumor having formed adhesions to the adjoining parts.

The patient was insensible to pain during the operation until the last attachment of the cyst was separated, when he exhibited signs of slight suffering, but asserted after the operation was over that the sensation of pain was so slight as scarcely to be perceived. In this operation the inhalation of ether ceasrd before the first incision was made. Since that time I have invariabh' desired patients, when practicable, to continue the inhalation during the time of the operation.

Having permitted such a length of time toelapse without making public my experiments in etherization, in order to show the correctness of my statements I procured the certificate of the patient on whom the first operation was performed, the certificate of two who were present at the time of the oper.ation, and also those of his mother, brothers and sisters and a number of his immediate friends who heard him speak of the operations soon after they were performed. The Southern ]Med. and Surg. Journal* contained but two of the certificates. I have a number of others which can be seen or read if desired by the Society. My third case was a negro boy who had a disease of a toe which rendered amputation necessary, and the operation was performed July 3rd, 18)2, without the boy evincing the slightest sign of pain.

These were all the surgical operations performed by me during the year 1842 upon patients etherized, no other case occurring in which I believed the inhalation of ether applicable. Since '42 I have performed one or more surgical operations annually, on patients in a state of etherization.

I procured some certificates in regard to these operations, but not with the same particularity as in regard to the first operations, from the fact of my sole object in the publication being to establish my claim to priority of discovery of power of ether to produce anasthesia. However, these certificates can be examined.

Tlie reasons which influenced me in not publishing earlier are .as follows:

I was anxious, before making my publication, to try etherization in a sufficient number of cases to fully satisfy my mind that an£Bstliesia was produced by the ether, and was not the effect of the imagination or owing to any peculiar insusceptibility to pain in the persons experimented on.

At the time I was experimenting with ether there were physicians high in authority and of justly distinguished character who were the advocates of mesmerism, and recommended the induction of the me.wierjcs/a?*' as adequate to prevent pain in surgical operations. Notwithstanding thus sanctioned I was an unbeliever in tlie science, and of the oiiinion that if the mesmeric state could be produced at all it was only on those of strong imaginations and weak minds, and was to be ascribed solely to the workings of the patient's imagination. Entertaining this opinion, I was the more particular in my experiments in etherization.

Surgical operations are not of frequent occurrence in a country practice, and especially in the practice of a young phj'sician, yet I was fortunate enough to meet with two cases in which I could satisfactorily test the anEesthetic power of ether. From one of these patients I removed three tumors the same day ; the inhalation of ether was used only in the second operation, and was effectual in preventing pain, while the patient suffered severely from the extirpation of the other tumors. In the other case I amputated two fingers of a negro boy ; the boy was etherized during one amputation and not during the other ; he suffered from one operation and was insensible during the other.

After fully satisfying myself of the power of ether to produce aniesthesia, I was desirous of administering it in a severer surgical


FAC-SIMILE OF LONG'S MANUSCRIPT. SEE PAGE 182.

operation than any I had performeii. In my practice, prior to the published account of the use of ether as an antesthetic, I had no opportunity of experimenting with it in a capital operation, my cases being confined, with one exception, to the extirpation of small tumors and the amputation of fingers and toes.

While cautiously experimenting with ether, as cases occurred, with the view of fully testing its antesthetic powers and its applicability to severe as well as minor surgical operations, others more favorably situated engaged in similar experiments, and consequently the publication of etherization did not " bide my time."

I know that I deferred the publication too long to receive any honor from the priority of discovery, but having by the persuasion of my friends presented my claim before the profession, I prefer that its correctness be fully investigated before the Med. Society. Should the society say that the claim, though well founded, is forfeited by not being presented earlier, I will cheerfully respond, so mote it be.

Not wishing to intrude upon the time of the Society, I have made this short compendium of all the material points stated in my article in the Journal, and if the Society wishes any fuller information on the subject I will cheerfully comply with their wishes.

Appendix II.

" Georgia, 1 I, Ange De Laperriere, M. D., do certify that I

Jackson County. > resided in Jefferson, Jackson County, Georgia, in the year 1842, and that some time in that year I heard James M. Venable, then of said county, speak of Dr. C. W. Long's cutting out two tumours from his neck while under the influence of the inhalation of sulphuric ether, without pain or being conscious of the performance of the operation.

I do further certify that the fact of Dr. C. W. Long using sulphuric ether by inhalation to prevent pain in surgical operations was frequently spoken of and notorious in the county of Jackson, Georgia, in the year of 1842. A. De Laperriere, M. D.

Sworn to and subscribed before me this 30th of March, 1854.

N. H. Pe.ndergrass, J. P."

"Athens, Clarke Co., Georgia. I, the undersigned, do certify that in May, 1843, 1 assisted Dr. R. D. Moore in amputating the leg of a colored boy Augustus, then the property of Mr. Wm. Stroud, who resided in this county ; and that I distinctly recollect hearing Dr. R. D. Moore say, If I had thought of it before leaving home I would have tried Dr. C. W. Long's great discovery, namely, the administration of sulphuric ether as an anaisthetic in performing the operation. Having neglected to bring the ether. Dr. Moore finally concluded to influence the


patient with morphia ; under which influence the operation was performed. Jos. B. Carlton, M. D."

Appendix III. From Dr. Long's First Student.

"CoHUTTA, Ga., Dec. 13th, 1894. Mrs. Frances Long Taylor,

Dea7' Madam :—* * * In 1844, soon after I attained my majority, I decided to adopt medicine as my profession, and began to think where and under whom I should begin the preparatory study. My father asked me to choose from among the number of physicians whom 1 knew the one I preferred to act as preceptor to me.

Knowing Dr. Long so well and believing him to be a man of no ordinary ability, I at once fixed upon him as my choice.

I entered Dr. Long's office in May, 1844, as the first student ever under his care. As I progressed with my studies he saw fit to make known to me his discovery, by the use of which he could perform surgical operations without giving any pain to his patient. [Here follows a description of the first cases.]

Notsatisfied, however, that there was not more to learn about this great disco very, he proposed that we test it further personally, which we did in his office, where with closed doors we administered it to each other to prove its perfect anaesthetic effect and also to discover any bad effect to the subject etherized. Owing to the prejudice and ignorance of the populace Dr. Long was prevented from using ether in as many cases as he might have.

Thus in the two years preceding my entering Dr. Long's office he had had only about six cases in which to try the anaesthetic effects of ether.

The first case thatcame under his care where its use was applicable after my going into his office was not till January 8th, 1845, which was the case of a negro boy having two fingers to amputate, caused by neglected burn. I, as the only student still with the doctor, he had me to accompany him to see the operation and assist ill the administration of the ether. The first finger was removed while under the influence of ether, the little fellow evincing no pain ; the second without ether, the child suffered extremely. This was done to prove that insensibility to pain was due to the agent used.

Soon after this, in January, Mr. J. D. Long came into the office as a fellow-student ; later, toward spring, came P. A. Wilhite, and in August came Dr. Long's brother, H. R. J. Long. We four remained there at Dr. Long's oflBce as students until the opening of the fall term of the medical colleges. » * *

[Signed] J. F. Groves, M. D.

Sworn and subscribed to before me, Dec. 15th, 1894.

\V.M. H. Wilson, N. P."


THE EARLY HISTORY OF OPHTHALMOLOGY AND OTOLOGY IN BALTIMORE (1800-1850).*

By Harhy Friedenwald, A. B., M. D., Associate Professor of Ophthilmologij and Otology, College of Fliysicians and Sii-rgcons,

Baltimore, Md.


An old book tells us that each generation may be looked upon as standing on the shoulders of its fathers. If its vision is clearer, its intellectual view less obstructed, its horizon broader, it is in great part due to the height to which others have raised it, to tlie support others have given. Unmindful of this, it is apt to exaggerate its greatness and the importance of its own work.


  • Read before the Johns Hopkius Hospital Historical Club,

April, 1897.


In the following narrative I have brought together all that I could find relating to tlie lives and labors of those who, in the earlier years of this century and in our own city, tilled the soil of ophthalmology and otology. Some have been forgotten, few have been accorded deserved recogniiion.

Are not many of us as ignorant of their names and works as an old physician from whose memories I liad hoped to obtain information, but whose response was, "No work was done in Baltimore in those departments of medicine before 1850"? I must confess tliat when iny attention was first drawn to this


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185


subject I knew of biit one work of importance which a Baltimore physician had rendered to ophthalmology.

There is no reference in literature to anything done in Baltimore in the two branches we are considering before the beginning of this century. We must remember that in 1800 the population of Baltimore City was 26,614 and that in 1802 there were but 44 physicians.

It is probable that there were here as elsewhere those who confined themselves to diseases of the eye. This is indicated by a resolution adopted at the convention of the Medical and Chirurgical Faculty of Maryland in 1805.* It was resolved that " the Board of Examiners be authorised to grant special licenses to dentists and occulists to practice in their respective branches, subjecting them to an examination only on the branches they possess; and that such licentiates shall pay ten dollars for each license so obtained; provided it shall be the opinion of the attorney-general that the law authorizes the examiners to grant such licenses. The secretary having submitted the preceding resolution to the then attorney-general, he gave it as his opinion that the law authorized the board to act according to the spirit of the resolution." These "occulists" did not, it appears, stand in very good repute.

In the review in 1825 of an American treatise on diseases of the eye, the writer, who was probably Dr. Isaac Hays, the distinguished editor of the American Journal of Medical Sciences and an ophthalmologist of note, describes the condition of ophthalmology in the early years of this century. He tells us that " the neglect to which disorders of the eye were too long consigned is truly astonishing. Prepossessed with an idea that there was something peculiar in the diseases attacking different parts, physicians entirely abandoned these affections to persons who were exclusively devoted to them and were totally ignorant of the laws which influence diseases of other organs. To this cause is to be attributed the slow progress which tlie science of ophthalmology made during many centuries. The history of this science shows that while it made most rapid advances in improvementby the investigations of medical men, it invariably, when abandoned to professed oculists, not only ceased to advance but actually retrograded ... In this country much apathy has existed, and we fear still exists, with regard to these affections. Some of our distinguished surgeons have not, it is true, entirely neglected them ; yet the mass of medical practitioners have paid little attention to them, and the science has advanced so rapidly during the few years that we believe few have kept pace with the improvements that have been made. The length of time that generally elapses before opinions of European writers are diffused in this country — the want of regular lectures — and above all, clinical instruction and the opportunities furnished of observing these diseases in institutions established for the reception of these cases, are the cause, no doubt, of the present state of the science among us."

He mentions that the New York Eye Infirmary was established in 1830, the Pennsylvania Infirmary for Diseases of the Eye and Ear in 1822, and "with respect to the institution at Baltimore he has but little information to communicate. It is


'Summary of Proceedings, &c., published in 1817


attached to the Baltimore Dispensary and is committed to the care of the author of this work." [Dr. Geo. Frick.]

Pierre Chatard.

The earliest Baltimore publication having reference to diseases of the eye is found in a paper written by Dr. Pierre Chatard in the Medical Repository, vol. VII, p. 28. Dr. Chatard was born and educated in France, and had settled in Baltimore in 1797. He was a prolific writer, the paper referred to being one of the earliest. It was entitled "An account of a case of Fistula Lachrymalis, with reflections on the diflerent modes of operating in that disease." The paper describes a case of lachrymal fistula relieved by introducing threads of silk after the manner of a seton through the lachrymal duct and gradually increasing their number. He discusses at length the various methods in vogue at that time of treating the disease. It is written in an interesting and elegant manner. None of the other writings of Chatard relate to diseases of the eye.

William Gibson.

During the second decade of this century the celebrated surgeon, Wm. Gibson, practiced in Baltimore. Win. Gibson was born in 1784 in Baltimore, and was graduated in medicine in Edinburgh in 1809. He was a physician to the Baltimore General Dispensary in 1818-19, and professor of surgery at the University of Maryland from 1812-19, resigning to occupy the same chair at the University of Pennsylvania from 1819-54. He died about 1858 (?)•

His numerous publications date mainly from the latter period of his activity, but there are two notable and very interesting references to ophthalmic surgery dating from the Baltimore period.

In Hirsch's History of Ophthalmology* we find the statement that Prof. Gibson of Baltimore had made the experiment of introducing a seton through the cataractous lens, witli the view of producing its absorption, so original an experiment that Hirsch cites the description given by Dr. John Revere untranslated. My friend. Dr. O'Connor of Boston, had the kindness of looking up the reference in the New England Journal of Medicine, vol. VIII, p. 119, of 1819, and I will give this account in full because of its intense interest.

Extract of a letter to one of the editors:

" lam desirous of communicating through the medium of the New England Journal a new mode of operating for cataract, which has been projected and jiracticed recently, in two cases, with the mot;t .satisfactory success, by my friend, Dr. Gibson, professor of surgery at the University of Maryland.

The operation was performed in the following manner : The iris was in the first place dilated by the application of atropa belladonna. A common sewing needle, slightly curved and armed with a single thread of silk, was then passed through the tunica sclerotica about two lines from the cornea, where the couching needle is usually introduced, through the opaque lens and out of the opposite side of the cornea, at a point corresponding to the one at which it was introduced. The silk being drawn through, and the ends cut off, a single thread was thus left passing through tlie ball of the eye, and acting on the diseased lens in the mauner of a seton. It


•Graefe and Saemisch's Handbuch, Vol. VII, p. 517.


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[Nos. 77-78.


was feared that serious inconvenience might arise from the irritation produced upon the tunica conjunctiva, from the excessive sensibility of this membrane. Fortunately, however, neither this nor any other accident intervened, and at tlie end of ten days, in both cases tlie diseased lens had disap])eared, and, in its place, the silk was distinctly seen passing like a bar across the pupil of the eye. Tlie silk was withdrawn, and in a few days the vision was restored. In the third and last case in wliich this operation was performed it failed in consequence of the iris being wounded. This caused such an inflammation of the organ that it was deemed proper to withdraw the seton at a very early period. This accident was attributed to not using the belladonna. One would think that a common sewing nee<lle is not the most convenient instrument that could be devised for this purpose, on account of the dense structure of the part througli wliich it is to pass, and the difficulty of having the perfect command of any instrument without a handle. From the nature ot the disease, from the known eflects of this remedy when applied to other parts of tlie body, and from the success which has already been experienced, there seems to be good reason to hope that this will be found an important improvement on the established practice in many forms, if not in every variety of the disease. But the practical benefit to be derived from this operation can only be tested by a more enlarged observation than in this country ever falls to the lot of any individual. I remain yours, J. Eeverb.

Balto.. Mch. 2nd. 1819."

We learn from Hirsch that Loewenhardt in 1828 operated in a similar manner for secondary cataract with anterior and posterior synechia, likewise with good resnlt; it ajopears that others have not attempted the operation.

In the American Appendix to the second edition of Cooper's Dictionary of Practical Surgery, edited in America in 1844 by David Meredith Keese, who in 1843 and 1843 was professor in Washington University of Baltimore, we find a very curious reference to Professor Gibson under the head of strabismus: "It apjiears from the Institutes of Surgery that Professor Gibson attempted the cure of strabismus by dividing the recti muscles of the eye, precisely as now practiced, some twenty years since, in Baltimore. Soon after he repeated it unsuccessfully in Philadelphia in several cases, and was induced to abandon it by unfavorable opinions exjiressed on the operation by Dr. Physick. He, however, inculcated the propriety of the operation upon his class many years since, and Dr. A. E. Hosack, of New York, then one of his pupils, distinctly recollects Dr. Gibson's expressions of confidence that the operation would ultimately succeed."

I had no little difiiciilty in finding the reference to which Dr. Reese refers. The first five editions of Gibson's Institutes of Surgery (published between 1824 and 1838) contain no chapter devoted to strabismus, and in the seventh edition the long account of strabismus and its treatment consists almost entirely in a paper written by Charles Bell and sent by him to Gibson. In this chapter the above reference is likewise not to be found. It is only in the sixth edition, published in 1841, that we find the reference. It is of such importance that I shall give it in detail. On page 375 Gibson states that:

"In the year 181S, while practising my profession extensively in Baltimore, the late Mr. B. J. consulted me about his daughter, a child of eleven or twelve years of age, both of whose eyes were directed very much inwards, and were thereby greatly deformed by a squint. I advised a pair of goggles, so contrived, by having a


small opening in the centre of each, as to oblige the ckild to direct the cornea to these openings, and by i)erseverance for several weeks, succeeded in diminishing the deformity but not effecting a cure. In the course of my visits the child remarked at different times that her eyes felt as if tied by a string. Struck with this observation, and conceiving the disease might depend upon shortening of the internal rectus muscle, I determined, the first opportunity, to try the result of divison of that muscle ; and as the friends of my young patient were unwilling the experiment should be first tried upon lier, I selected a hospital patient, and after some difficulty in fixing the eyeball and in cutting the muscle across, succeeded in restoring the eye partially to its natural situation. Upontwoother patients I repeated the experiment, without mucli better success, but on dividing a muscle in a fourth patient, after my removal to Philadelphia, the eye was so completely turned to the opposite direction as to bury the cornea beneath the lids and create a much greater deformity tlian liad previously existed. Upon showing the patient to Dr. Physick, he advised the experiments to be abandoned, as likely to be followed by very unfavorable results. I mention these circumstances, not from a desire to receive credit as an inventor or to detract from the claims of the distinguisiied surgeon with whom the modern operationof strabismus originated, but merely as a curious fact, calculating to show the importance of not laying aside processes apparently founded upon correct principles, simply because we are at first foiled in our attempts to execute them. How much benefit would have resulted to the community if I had followed up my operations until I ascertained the proper mode of correcting them, or how much injury I might have inflicted upon individuals by perseverance in ihe attempt, I shall not stop to inquire. It is sufficient for me to announce the fact — wliich I have no doubt could be easily substantiated by many pupils who attended my early lectures, some of whom have indeed already proffered their testimony — without being over-solicitous, in setting up a claim as an inventor, of exposing my aw kwardness and perhaps want of knowledge of the principles that should have guided me in following out the practice I had attempted to institute."

It may not be out of place to mention that; Stromeyer's important monograph, in which he recommended division of the muscle for strabismus appeared in 1838!

The chapters devoted to diseases of the eye in Gibson's Institutes are important, but as the book appeared after the author had left Baltimore, it is not proper to discuss them here.

Another reference which shows Gibson's interest in the eye occurs in the American Medical Eecorder (vol. II, p. 383). It is a "Letter of Charles Bell to Professor Gibson, of Baltimore," and its subject is, " The New Coat of the Eye discovered by McCarthy's demonstrator, Jacobs."

George Fkick.*

We may next take up the most important name of this narrative, that of Dr. George Frick, the author of a valuable treatise on diseases of the eye, the first ^\■ork of the kind that appeared in America.

George Frick was born in Baltimore in 1703. After obtaining a broad classical education he entered the University of Pennsylvania, where he obtained the degree of doctor of medi


  • The accompanying portrait of Dr. Frick is copied from one

recently presented to the Medical andChirurgical Faculty, together with a case of instruments which belonged to the doctor, by his niece, Mrs. AVhite and her daughter. Miss Mary White.


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JOHNS HOPKINS HOSPITAL BULLETIN.


187


cine in 1815, and in 1&17 he was admitted as licentiate of medicine into the Medical and C'hirurgical Faculty of Maryland. He then spent several years abroad, returning to Baltimore about 1819 to engage in the practice of ophthalmology. He was api)ointed surgeon to the Baltimore General Dispensary, where he established the first Eye Dispensary in Baltimore, in 1824. In 18^3 he delivered clinical lectures at the Maryland Hospital. His name is found on the list of vaccine physicians for 1821.

He was a member of various medical societies; was secretary of the Faculty in 1823, and joined the Maryland Medical Society in 1822. He was much interested in general science, and was one of four physicians to organize a society for promoting science, in 1819. He was likewise a member of the Maryland Academy of Sciences, its librarian in 1824 and curator in 1836.

He devoted himself to the practice of ophthalmology and to the cultivation of general scientific stvrdies, as well as to music for a number of years. He was unfortunate in growing very deaf before middle life, and it is probable that this interfered greatly with his practice of medicine ; for somewhere about 1840 he entirely relinquished it and left Baltimore to spend most of his time in Europe, paying occasional visits to this country. He died in Dresden, March 36th, 1870, aged 77 years. Dr. Frick had never married. He was a man of very retiring and modest character and of kind disposition. He was a careful scientific student and his work and writings deserve high praise.

His first writing was his thesis for the degree in medicine; its subject was "On the Meloe Vfsicatorium" (1815). In 1820-31 his article on " Observations on Cataract and the various modes of operating for its cure" appeared in the American Medical Kecorder of Philadelphia. These articles cover over 40 pages. In 1821 an article on "Observation of the various forms of Conjunctivitis" appeared in the same journal, and in 1823 his paper on " Observation on Artificial Pupil and the modes of operating for its cure."* His most important work, however, was "A Treatise on the Diseases of the Eye; including the doctrines and practice of the most eminent modern surgeons and particularly those of

  • This curious error is cited as it is found.



Professor Beer," which was published in Baltimore by Fielding Lucas, .Jr., in 1823. It was inscribed to his teachei-, Dr. Physick of Philadelphia. The articles above referred to, though somewhat more elaborate, were in the main identical with the corresponding chapters of the treatise and do not therefore require special consideration. The treatise is of considerable value.* It is well and clearly written, the system irpon which it is classified is excellent, and no greater praise could be given it than stating the fact that it was republished three years lateiin London by an English surgeon, Richard Welbank, a member of the Royal College of Surgeons and of the Medical and Chirurgical Society of London, and dedicated to the ophthalmologist William Lawrence. Numerous foot-notes were added, but the te-xt suffered no change.

The reviews which the book received were very complimentary. The Philadelphia Journal of Medical and Physical Sciences (probably Dr. Isaac Hays) contains a review covering 18 pages: "The author evidently possesses a cultivated and well disciplined mind; he appears to be intimately familiar with German writers, and we feel much indebted to him for making us acquainted with their writings."

In the American Medical Recorder of 1824 a still longer review is to be found, covering 32 pages. The writer describes the book in terms of high praise. He "offers the humble tribute of (his) thanks to the author for the benefits which he has conferred on the profession generally, by presenting them with a volume of great value and utility, and one which was much


  • It is interesting to find numerous pencil notes in the articles in

the copies of the American Medical Recorder at the library of tlie Medical and Chirurgical Faculty of Maryland, notes suggesting slight changes in the phraseology, paragrap'-ing, etc., every one of which has been adopted in the treatise. I have been able to trace this copy, which was bought with other books by Dr. ,Iohn Morris at a public sale of the library of Dr. John Buckler, who was related by marriage to Dr. Frick, and whose library thus passed into Dr. Buckler's. Numerous books at our library contain Dr. Frick's autograph, and one, a copy of Gibson's Institutes of Surgery, has an inscription of the author to his friend Dr. Frick. In Beer's work on ophthalmology there are interesting pencil notes and several pages of written matter which correspond so thoroughly with Dr. Frick's writing that I have no hesitation in stating that tbev are his.


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[Nos. 77-78.


wanted. As a manual of the diseases of the eye, we believe it to be the best which has been published. It contains all the improvements which have enriched ophthalmic surgery, in such a siirpi'ising degree within a few years past," etc.

In 1835 this work was placed on the list of those which the student was required to liave read before applying to the Medical and Chirurgical Faculty of Maryland for the examination for licentiate in medicine.

Hirsch in his history of ophthalmology says that " George Frick was the apostle of the ophthalmological school of Vienna in North America; his treatise was next to Saunders's, the first large treatise on ophthalmology in America, and was received by physicians with great praise." Saunders's book was an English work and was republished in Philadelphia in 1831, two years before Frick's. The only other book in the English language of a similar kind was that of Travers, which appeared in London in 1820-31-24.

We thus see that Frick's book was the first American treatise (and for a number of years it remained alone). The work is much quoted in Cooper's Dictionary of Surgery.

In Quinan's Medical Annals of Baltimore I find a reference to a paper of Dr. Frick's " On the Senses," which he tells us was read before the Medical Society of Maryland in 1821. I have been unable to find this paper.

In Cordell's History of the University of Maryland we learn that the foiindation of the Infirmary was laid in 1823 and that patients were received in the same year. Of the four wards, "one was reserved for eye cases, instruction in ophthalmic surgery forming a prominent feature in the course. This was during the time of Frick's greatest activity, and it is possible that the prominence given to ophthalmology was through him, and that he delivered the clinical lectures in this branch. I am unable to verify this.

In conclusion it is interesting to call attention to the fact that Dr. George Frick was the uncle of the distinguished clinician, Professor Charles Frick.

Horatio G. Jameson.

Horatio G. Jameson, born in Pennsylvania about 1793, graduated in medicine at the University of Maryland in 1813. He held a number of important public positions, having been consulting surgeon of the Baltimore City Hospital from 1819 to 1835, consulting physician of the board of healtli of Baltimore City in 1827-35 ; he was incorporator of the AVashington Medical University in 1827, and professor of surgery and surgical anatomy in the same from 1827-35, when he became professor of surgery in the Cincinnati Medical College. He was one of the most prominent surgeons of Baltimore for a number of years, and a very active contributor to medical journals, writing important papers in medicine and in surgery. He was the editor of the Maryland Medical Recorder during its existence of several years (Sept. 1829-Nov. 1832), and a large number of its articles are from his pen.

Jameson appears to have been much interested in diseases of the eye. AVe find frequent references to publications on these subjects throughout his journal, several of which have remarks added by the editor. In vol. 2 there is an article on the


"Pathological Sympathy between Eye and Larynx" (p. 117) This article is without any value, indeed it is difficult to understand the real significance of his report after careful reading. An article on "A case of Enlargement of the Eye following the entrance of steel into the eye" describes the panophthalmitis followed by bursting and shrinking of the eyeball (p. 601).

In another paper he described " two cases of ossification of the lens with luxation through the pupil." These cases are of some interest. He extracted the lenses and the patients did well (p. 608). An article on amaurosis associated with inordinate thirst was probably written by Jameson (p. 664).

In the American Medical Recorder of Philadelphia (vol. XII, p. 340) we find an interesting account of the successful removal of " An encysted tumor of tiie orbit."

In discussing a letter on "Ophthalmia in the Philadelphia Alms House," written to Dr. Rusii, Jameson considers the question of the endemic or .contagious character of the ophthalmia, excludes the latter view, and attributes the very severe disease to the vitiated state of the atmosphere. He states that " we do not as a general rule of practice bleed sufficiently in cases of ophthalmia."

John Mason Gibson.

John Mason Gibson in 1832 published in Baltimore (W. R. Lucas) a " Condensation of Matter ujwn the Anatomy, Surgical Oj)erations and Treatment of Diseases of the Eye, together with remarks. Embellished with twelve lithographic plates, illustrative of the anatomy, operations, and morbid appearance."

I am unable to give any details of this author's life. I find that he vvas admitted into the Faculty in 1825, and that his name appears as late as 1848 in the list of members with the title of L. M. In the next succeeding list published in ISoS Gibson's name is missing.

In the preface he tells us that his book is an " attempt at collecting the best matter on diseases of the eye." That " diseases casiral to vision are many and frequently met with in this country; the curative practice has not been sufficiently inculcated in our universities, by impressing upon the mind of the student where and when the importance and great nicety of judgment are requisite in the treatment of them, and that by inadvertent and mal-practice the victim may grope through his existence here in the valley of darkness."

The work is one of compilation, "being made up of exten- f

sive quotations from the classical writers of the day." He claims originality only in the construction of his plates, and so far he is certainly correct, for the drawings are quite unlike anything seen in nature.

The arrangement of the work is very curious. The chapters follow in this order: Anatomy of the eyeball, cataract, ophthalmia, corneitis, iritis, choroiditis, retinitis, inflammation of the lens and its capsule, ulcers of the cornea, ojiacities of the cornea, ptergium, prolapse of the iris, extirpation of the eyeball, extraneous bodies, diseases of the lachrymal apparatus, under which is included entropium, ectropiuni, epiphorn, encaiitlius, injury of lids, ophthalmia tarsi and fistula hiclirv


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malis, looking very much as tlioxigh the subjects had been drawn haphazard from a grab-bag.*

At the end of several chapters the author adds original remarks. When we consider the very excellent and systematic work which Frick had published, nine years previously, as well as such other works from which copious quotations are made, it is quite inexplicable why Gibson showed such disregard of systematic classification, or indeed what purpose he had in publishing the work at all.

Dr. John Hakper.

Dr. David Jleredith Reese, in his American edition of Cooper's Dictionary of Practical Surgery, first published in 1833, tells us, under the section of cataract, that "one of the most successful operators in this country is Dr. John Harper, of Baltimore, and he seldom adopts any other operation than this (laceration of the capsule and lens substance), which he repeats as often as necessary on the same eye." I have given myself great pains to obtain some information concerning this " successful operator," but his memories appear to have been completely effaced. One single reference is to be found, a short obituary notice. In the Maryland Medical Recorder (vol. II, 179) there is a notice of the death of four members of the Medical and Chirurgical Faculty of the State of Maryland. One of these reads as follows : " Died in the month of January, 1831, Doctor John Harper. Doctor Harper was a native of Ireland, and graduated at Ghisgow. He was wellknown as an oculist." The title of oculist appears to have been elevated to the dignity of a special practice of medicine within a few years. For Harper was a member of the Faculty, and not of the despised class of oculists mentioned in the beginning of this paper.

William Alexander Clendinen.

Wni. A. Clendinen graduated in the medical department of the University of Maryland in 1840, a classmate of Dr. G. W. Miltenberger. He died of cholera at New Orleans in 18-1:9, having been seized with the disease while dissecting a victim of the epidemic. After his graduation he traveled extensively, devoting his time to the study of medicine. In the Boston Medical and Surgical Journal in 1847 we find several papers which were translations from the work of Prof. Desmarres. In his letter to the editors he tells us that the extracts are part of a "translation upon which he is now engaged"; he expresses his gratitude to Prof. Desmarres, who " has entrusted to him an onerous but useful task, one which from (his) connection with him (he) may be able to perform advantageously to readers of the English language." In the second article, published in the same journal, we find after the name of the author, " Chef de la clinique oculaire." There were in all but three articles, and the promised book never made its appearance, perhaps on acco^^nt of the untimely death of the author.


  • Not a few important subjects are entirely ignored, viz. errors

of refraction, strabismus, etc.


OTOLOGY.

The early contributions to Otology in Baltimore were very few. Two names deserve recognition ; the first of these is that of the renowned surgeon,

Nathan Rhyno Sjiith.

It is beyond the province of this paper to give a biographical sketch of Dr. Smith. A very complete sketch can be found in Dr. Cordell's History of the University of Maryland. He was born in 1797 in New Hampshire, graduated as A. M. in 1817, and as M. D. in 18-^3 in Yale College. He was professor of anatomy and surgery in the University of Vermont in 1825, soon leaving to occupy the chair of anatomy in the newly organized Jefferson Medical College of Philadelphia. From 1827-39 he was professor of anatomy in the University of Maryland, and from 1829-38 he occupied the chair of surgery at the same university, leaving this for three years to occupy the chair of theory and practice in the Transylvania University. He resumed it again in 1841 and held it until 1869.

One of the earliest writings of this prolific worker was the translation of a treatise on the ear from the French of Saissy,* with additions by the translator on diseases of the external ear. This book was published in Baltimore in 1829, and was, so far as I can learn, the second book on diseases of the ear printed in America, the first having been an American edition of Saunders on the eye and ear in 1821.

Saissy's work was "highly esteemed in France," and was one of the important factors in the revival of modern otology. In his preface Dr. Smith tells us that " a concise manual on the diseases of the ear is an acknowledged desideratum in our medical literature. No sufficient work on the subject has ever been issued from the American press. With a view to supply this deficiency (he has) translated the following pages from the French of Saissy . . . corrected and enlarged by its author, and after his death published in 1827 by his friend Montaion, etc.

" It embodies the excellencies of Saunders, Cooper, Leschevin, Maunoir, Itard and Alard . . .

" The attention of the reader will be particularly occupied with Saissy's excellent method of injecting the ear through the eustachian tube. We very well know how frequently the external ear is obstructed by its own secretions, free as is their egress from this cavity. The internal ear is also lined with a membrane which furnishes an excrementitious fluid. It can escape only by the narrow channel of the eustachian tube. How frequently then must it be delayed in the cavity of the tympanum and mastoid cells, giving rise to any degree of mischief."

To render " the work more complete and useful to the medical pupil (he has) added a brief supplement on diseases of the external ear. On this score, however, (he) claims nothing, as (his) addition is made up of commonplace iirinciples and


  • An Essay on the Diseases of the Internal Ear, by J. A. Saissy,

M. D., translated from the French by Nathan Rhyno Smith, M. D., Professor of Surgery in the University of Maryland, with a supplement on Diseases of the External Ear, by the translator. Published by Hatch & Dunning, Baltimore, 1829.


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[Nos. 77-78.


precepts subjoined merely for the purpose named above." He concludes: "I have, it is true, for perforating tlie tympanum devised a new instrument wliich I trust will be useful."

The part of the book most interesting to us is the supplement on diseases of the external ear, covering about twenty pages. These chapters are written in the most concise and simple manner and cover most of the inflammatory afiections of the auditory canal, congenital deformities, injuries as well as the treatment of foreign bodies, insects and indurated wax in the auditory canal.

He describes his method of inspecting the canal as being " best accomplished by placing the head in such an attitude as to suffer the sun's rays to enter the meatus and impinge upon the tympanum. To effect this, the operator must seize the external ear, and drawing it outward from the head, extend and straighten the cartilaginous part of the meatus. I have been able to inspect the ear more perfectly by introducing, at the same moment, a steel director, with its groove toward the meatus and its convex side pressed firmly against the anterior walls. The passage is thereby straightened and expanded. If there be no wax present the tympanum will be seen of a pearly white color and concave."

The little instrument which he devised for perforating the membrani tympaui is a minute trephine, by revolving which a circular piece of the drum was excised. His object in constructing this instrument was to obtain a larger opening, for he tells us that in two instances in which he had occasion to perforate the membrani tympani he found the beneficial effects of the operation soon to cease in consequence of the speedy closure of the artificial opening. The Maryland Medical Recorder of 1839 reviews the work extensively, the review covering twenty pages. The review is by no means flattering.

It is very apparent that Dr. Nathan R. Smith must have been deeply interested in the subject of the diseases of the ear. He had an extensive j^ractice in diseases of the ear, and also of the eye, though none of his publications deal with the latter organ. Dr. Theobald has recently found a drawing of a knife designed by Dr. Smith to slit the lachrymal canal.

Dr. Joshua I. Cohen.

Dr. Cohen, born in Maryland in 1800, graduated at the University of Maryland in 1833, having been a student in Dr. Nathaniel Potter's office, and soon after devoted himself to the study of diseases of the ear. He was an intimate friend of Dr. George Frick, the oculist, and, like his friend, had wide interest in science beyond the domain of medicine. He thus for a time became professor of mineralogy in the academic department of the University of Maryland. He was much interested in the Medical and Chirurgical Faculty of Maryland, was its treasurer from 1839 to 1856 and president from 57-58. He was also much interested in the Maryland Academy of Sciences.

He practiced until about 1851, devoting himself almost exclusively to otology. His reputation as an aurist must have been quite great, for we read in Reese's American edition of Cooper's Dictionary of Practical Surgery (2nd ed., vol. 2, p. 73, under the heading "Ear"): "In the United States there have been a few surgeons who have distinguished themselves by their success in the treatment of diseases of the ear.


" Dr. Cohen of Baltimore and Dr. Dix of Boston have for several years directed their particular attention to diseases of the internal ear, and to the investigation of the abnormal condition of the tympanum and eustachian tube in cases of deafness. These gentlemen have employed condensing apparatus for administering the air douche through the eustachian tube after the plan of Kramer and others. By the air and also by the water douche, these gentlemen have acquired great tact in the diagnosis and treatment of obstructions in the tube and upon the tympanum."

In 1840 he established, in connection with his friend, Dr. Samuel Chew, an eye and ear institute in Baltimore, in which Dr. Chew had charge of the eye department. Dr. S. C. Chew has had the kindness to inform me that this association between Dr. Cohen and bis father lasted for a short time, as his father's appointment to a chair in the University of Maryland compelled him to withdraw from it.

Dr. Cohen was one of the earliest, perhaps the first, aurist in this country. He has left us, however, but one publication which pertains to diseases of the ear. It is entitled " Postmortem Appearances in a Case of Deafness."* The paper is very short, but is written in the most scientific manner.

In a note written by the editor of the Journal we read that this "valuable communication was read before the American Philosophical Society, at a recent meeting, and is noticed in the proceedings of that body. It has rarely happened that opportunities have been embraced for examining into the condition of the organ of hearing in cases of deafness, or that they have fallen within the observation of an investigator so competent as the author of this paper." The case was that of a patient who died of phthisis. The brain and seventh pair of nerves were examined carefully, but no changes observed. The lower part of the skull was then removed and the ear examined in minute detail.

In the right ear he found the drum-head dull and dark in appearance, irregularly thickened and retracted as a whole, thus diminishing the cavity of the tympanum. The tympanum itself was filled with muco-fibrous membranes passing from the membrani tympani to the posterior walls, presenting a cellular structure. These were carefully divided, exposing the tensor tympani muscle, the tendon of which was found to be of unusual shortness and attached to the handle of the hammer throughout its whole length, thus drawing the bone and the membrani tympani to within a line of cochlear process. Interesting irregularities in the ossicula were noted. The malleus was normal. The incus was undeveloped, diminutive in size. The stapes was wanting with the exception of the base, which was held in place by the circular ligament. The depression of the oval window was filled with membranous tissue, which likewise covered the fenestra rotunda. The tensor tympani muscle was strongly developed, its tendon short and thick as mentioned above. The stapedius muscle existed, but there was no tendon.

In the left ear the membrana tympani was found to have been entirely destroyed, with the exception of a very thin slip at the anterior inferior edge. The tympanum contained a


•Amer. Med. Intelligencer, July 1841 to July 1S42, p. 220 (Vol.1).


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quantity of yellowish fetid matter, and its lining membrane was completely disorganized. The union between the ossicula was slight, owing to the general disorganization of the ligamentous and mnco-fibroiis connections. The incus was in place, but the handle of the malleus was depressed. The stapes was not bound down in the oval window, for the annular ligament was entirely destroyed. Tiie tendon of the tensor tympani was disorganized and that of the stapedius destroyed; the whole condition of tiie tympanum showed a recent active suppuration which did not confine itself to this part; the vestibule was penetrated as well as the mastoid cells; the latter were covered with pus. Tlie cochlea and one of the semicircular canals were examined a day or two subsequently, but there was nothing remarkable about them at this time worthy of note.

Inquiry about the patient led the author to conclude that the faculty of hearing in the right earhad been entirely wantingor was very much impaired for many years.

Though he seems to regard the condition of the right ear to have been congenital, his critical analysis is as acute as the observations tliemselves are accurate. He cites cases of Morgagni in which membranes filled the cavity of the tympanum.


and another in which there was immobility or contracture of the muscles. At the conclusion of his paper he says: "In the case described in this paper, does not the absence of every part of the stapes, with the exception of the base, liken it to the osseous operculum found in the bombinatores, land salamander, and cfBciliffi ; of the effect of wliich, in the communication of sonoro:is undulations, I have already spoken ? " I am unable to find any other reference to this paper on undulations and do not know whether it was ever published.

This sketch must be brouglit to a close. Is it necessary to remark what any careful reader must have observed, that there were physicians in Baltimore in the first half of this century who labored faithfully and well in Ophthalmology and Otology? Their contributions were among the earliest and most important in this country.

In conclusion I desire to express my thanks to Dr. G. W. Miltenberger, to Dr. John Morris and to Dr. Eugene F. Cordell, who furnished me with important notes, as well as my indebtedness to Dr. John R. Quinan's "Jledical Annalsof Baltimore," and Dr. Cordell's " History of the Universiiy of Maryland."


JOSEPH FRIEDERICH PIRINGER: HIS METHODS AND INVESTIGATIONS.*

By Harry Friedenwald, A. B., M. D., Baltimore.


"Joseph FreiJerich Piringer was born, March 31st, 1800, in Klein-Zell in Upper Austria. He studied medicine in Vienna ; he afterwards turned his attention to ophthalmology in 1824. He was at first an assistant of Jaeger, then for three years of Rosas (beginning in 1825). He next obtained the extraordinary professorship of ophlhalmology in the medical school at Gratz. Here he founded a much-needed eye hospital, an institution out of which the ophthalmic department of the AUgemeines Krankenhaus gradually developed through his energy. Here he held a high position and was active as a teacher until ISGO. His clinical and experimental stuilies on blennorrhcea were made at this hospital. He wrote a work on blennorrho;a which was awarded a prize by the German Society of Physicians in St. Petersburg. Piringer has the merit of having shown that intentional infection of blennorrhceic secretion in pannus leads to clearing of the cornea. He founded a reputation upon this which extended far beyond the boundaries of Germany. He was for many years attached, as visiting physician, to the Elizabeth Hospital and to the City Asylum for the Aged, and published several other articles up to the time of his death, Sept. 22nd, 1879, including: Ueber Veratrinbehandlung des acuten Gelenk-Rheumatismus ; Die Behandlung der Variola mittelst lodtiuctur; Die richtige Pflege der neugebornen und kleinen Kinder ; Studien ueber die MortalitatsStatietik in Graz."f — (From Hirsch's Biographisches Lexikon, 1886, vol. IV, p. 575.)

Piringer's work on blennorrbceaj was awarded a prize, and the earlier works in ophtiialmology refer to his studies, especially to his investigations in the treatment of pannus.§ Arlt


•Read before the Johns Hopkins Hospital Historical Club. 1 1 am indebted to Professor Wm. H. Welch for having called my attention to this account of Piringer's life.

t Die Blennorrhoe am ^Menschenauge. Graz, 1841. lOest. Med. Jahrb., 1838, and chapter 8 of the monograph.


devotes some space to a summary of the work on blenuorrhcea.* But more recent works in ophthalmology make no mention of these important studies and their no less important results; in works on bacteriology I do not find his name, nor even in works on gonorrhcEa, such as that of Finger. Piringer's work was of such importance that it does not deserve to be thus forgotten.

The absence of any other references in ophthalmic literature leads me to believe that Piringer's studies in ophthalmology were confined to the subject of inquiry contained in the work above mentioned. This is the more readily understood when we read in his preface " that his itntiring efibrts during fifteen years were given up to the solution of the natural laws governing blennorrhoeas of the eye, as far as this lay in the limited powers of a single individual." We may aptly apply to Piringer the words, "therefore by their fruits ye sliall know them." Judged by this standard, Piringer stands out boldly as one of the greater luminaries of medical science in tlie first half of this century.

In order to properly estimate the importance of his investigations it will be necessary to examine into the state of knowledge of the subject previous to 1840.

In 1780 a treatise on diseases of the eye appeared, written by George Chandler, surgeon, of London, in which he gives this account of "venereal ophthalmy." He divides it into two varieties, the translative and the symptomatic.

"The translative ophthalmy begins with a copious discharge of a sebaceous humor of a yellowish white color, and is known by the tumor, lividness, sharp and lancing pain of tlie sclerotica, the


  • Klin. Daratellung d. Krankheiten d. Auges. Vienna, 18S1, pp.

35-37.


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[Nos. 77-78.


cornea at the same time being as it were depressed within a pit. It frequently follows soon after an injudicious stoppage of a gonorrhoea, the venereal virus being translated into the eye. It has also been observed that a gonorrhoea which before seemed incurable has, upon the coming on of this ophthalmy, suddenly vanished ; and in like manner the ophthalmy has gone off upon the return of the gonorrha?a . . . The symptomatic remits towards morning, never turns into a chemosis, the morbid matter does not change place, the pains are milder, it is removed when the hies is cured, and is also attended with less danger."

He admits that "sometimes a venereal ophthalmy has been produced by the immediate application of the virus to the eyes."

Concerning the treatment he tells us that —

"The venereal ophthalmy in general is subdued and its poison extinguished by mercury, but it should never be applied to the eyes. The patient should be bled and purged, and his eye washed continually with brandy and water, etc. It is necessary also to evacuate the virulent matter collected in the cellular texture of the sclerotica and eyelids by slight incisions of each membrane ; an ichor, very like that of gonorrhtea, will be discharged."

This was the older view.

About the beginning of this century a remarkable development occurred in ophthalmology. Beer and Schmidt in Vienna, and Himly, Langenbeck, Graefe the elder, and others gave a new impetus to the scientific study of this branch of medicine. This was followed by the publication of a number of important treatises and monographs in ophthalmology, principally in Austria and Germany, but also in France, England and our own country. I shall pass these by and take up the subject as we find it in the third edition of one of the most important and valuable treatises on " Diseases of the Eye " written in the first half of this century, that of William Mackenzie of Glasgow. I take the third edition as it appeared in 1840, one year before Piringer's work. Here we find under the section of ophthalmia in new-born children, that "there is reason to suspect that this disease is not unfrequently an inoculation of the conjunctiva," etc., and "that therefore it may often be prevented by carefully washing the eyes of the infant with tepid water," etc.; secondly, "that the purulent ophthalmia of infants in its worst form is the result of the application of gonorrhceal matter, is generally admitted."

Concerning gonorrha'al ophthalmia he tells us that —

" Different views have been entertained of the purulent inflammation of the conjunctiva which is frequently found to attend or succeed gonorrhtea. First, this ophthalmia has been ascribed to inoculation with matter from the urethra; secondly, it has been supposed to be metastatic ; and thirdly, it has been considered, at least in certain cases, as an effect owing to irritation merely, without either inoculation or metastasis. It is quite possible that there may be three such varieties of this ophthalmia. The existence of the first I consider beyond all doubt ; but the second and third are somewhat problematical."

His description of the first form is quite clear, and in several cases which he reports the infection is definitely proved. He did not succeed in separating gonorrhcEal from what was called Egyptian ophthalmia, excepting as differing in degree. This distinction was not definitely made until about ten years later (by Bendz). Mackenzie's criticism of the views entertained by


some eminent ophthalmologists is so interesting that I shall quote the entire paragraph:

" Dr. Vetch tells us that in a soldier in a very advanced stage of Egyptian oplithalmia he attempted to divert the disease from the eyes to the urethra, by applying some of the matter taken from the eyes to the orifice of the urethra. No effect followed this trial. It was repeated in some other patients, all laboring under the most virulent state of the Egyptian disease; and in all the application was perfectly innocuous. But in another case, where the matter was taken from the eye of one man laboring under i)urulent ophthalmia, and applied to the urethra of another, the purulent inflammation commenced in 36 hours afterwards and became a very severe attack of gonorrhrea. From the result of these experiments, Dr. Vetch, while he admits that gonorrhceal matter taken from one person and applied to the conjunctiva of another will excite a highly purulent ophthalmia, regards himself justified in no longer admitting the possibility of infection being conveyed to the eyes from the gonorrhceal discharge of the same person. He adds that the impossibility of this effect was rendered decisive by an hospital assistant who, with more faith than prudence, conveyed the matter of a gonorrhcea into his eyes without any affection of the conjunctiva being the consequence. It is remarkable that Dr. Guillie has fallen into the same error of reasoning as Dr. Vetch, onlythathis negative experiments have led him to the very opposite conclusion. He applied the matter taken from the conjunctiva of one patient to the urethra of another; no effect followed, and hence he concludes that the notion of some regarding the propagation of puro-mucous inflammation from one mucous membrane to another in different individuals, is unfounded."

Mackenzie, however, devotes considerable space to the discussion of gonorrhceal ophthalmia from metastasis, though nothing could be better than his statement that writers had adopted these views " with too little hesitation and appear not to have sufficiently investigated the probability of the ophthalmia arising rather from inoculation than from metastasis." He goes on to enumerate " the causes of the suppression of the gonorrhcea, to which the rise of metastatic gonorrhct-al ophthalmia is attributed," and cites an illustrative case from a French writer. It is evident that ilackenzie had little confidence in the existence of this form of gonorrhceal ophthalmia.

A third form of gonorrhceal ophthalmia without inoculation or metastasis is described : "an alternation has been observed between the two diseases; that is to say, when the gonorrhcea came, the ophthalmia went, and vice versa." Mackenzie says that the cases reported "show the diversity which exists in opinions entertained regarding the ophthalmiaj which in some individuals are found to attend gonorrha'a, or to alternate with this disease"; and that "it is quite evident that the ophthalmia? which have been observed to do so are far from being uniform," that some are probably ophthalmia tarsi, others catarrhal ophthalmia. What is most important is his statement that '■ it may fairly be doubted whether there is any connexion between diseases of urethra and that of the eye, farther than that they occurred in the same iudividtials, while the occurrence of both might be attributed to a susceptibility for disease arising from peculiar or debilitated constitutions." We are somewhat surprised to see this statement followed by such a one as this, that "Swediar's hint to employ the bougie in cases of ophthalmia alternating with gonorrhcva may probably be found of use; it is evident, however, that this remedy cannot be trusted alone, but that the ophthalmia must be treated according to


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the particular symptoms it presents, not according to tlie conjectural notions entertained regarding its origin." Concerning Egyptian ophthalmia jMackenzie says:

"I think it probable that the ophthalmia which attacked the British anil the French armies in Egj'pt was an atmospheric puro-mucous conjunctivitis [described at another place as "excited by exposure to atmospheric alternations "], but that it afterwards degenerated into a contagious, perhaps infectious disease; that is to say, that it was propagated by actual contact of the discharge, and perhaps by miasmata from the eyes floating through the air."

Mackenzie's views may fairly be taken as the most advanced of this period and will serve as the proper point from which to view the investigations of Piringer.

It should be mentioned here that many subsequent writers held on tenaciously to these and older views for many years after Piringer's discovery had been made.

We may first direct our attention to Piringer's experiments in curing pannns by producing acute purulent ophthalmia. This method, we are told, was first suggested by Friederich Jiiger* some time during the second decade of this century, but little or no attention had been given it before Piringer's experiments were made. He tried the metliod in more than sixty cases, using the pus of various kinds and stages of purulent ophthalmia of bo(h adult and new-born. All of his cases were improved and not one was injured by the treatment. In the great majority of cases the cure was complete, so that no sign of the former disease could be discovered, and permanent. He therefore recommends this method of curing paunus in these words: "After so many highly successful experiments and observations, the inoculation of tlie blennorrhoea for the cure of pannus is no longer a doubtful measure which requires great courage, but an excellent method (ein grossartiges llittel)." This method remained in use for many years and is still being applied in a modified manner. The modification consists in the use of jequirity to produce a purulent ophthalmia instead of blennorrhceic matter.

It was in the study of this method of treatment that Piringer made his investigations as to the nature of blennorrhceaand the contagious property of the secretion. For this purjjose his experiments were varied inevery conceivable manner. Most of the experiments were made upon eyes which were already diseased, but these were controlled by other experiments upon amaurotic eyes with perfectly healthy conjunctiva, or by the accidental infection of normal eyes.

After describing the various forms of purulent inflammation of the conjunctiva he takes up the causes. Under this head he discusses the question as to the production of gonorrhoeal ophthalmia by metastasis. In the course of fifteen years he had never seen a case of suppression of a gonorrhoea with an outbreak at another point, excepting in the neighboring tissues.


  • In Hirsch's History of Ophthalmology, p. 441, we read thatLudwig reported the successful use of this method at the hands of a

friend, probably Friederich Jiiger.

Wharton Jones (in a manual on Ophth. Med. and Surg, published in 1847) states that Dr. Henry Walker was the first to suggest the method (Edinburgh Medical and Surgical Recorder) in 1811. I am unable to verify this citation.


Many physicians of great practice had likewise never seen true metatastic gonorrhcsal ophthalmia. He denies the occurrence of such a form of disease, and characterizes it as a very pretty fable which one after the other has been telling in the best of faith. Gonorrhceal ophthalmia is always due to the transference of infectious material directly into the conjunctiva!

In a similar manner he disproves the existence of a consensual form of gonorrhceal ophthalmia, supposed to be due to a sympathetic connection between the affected parts.

Gonorrhceal ophthalmia is known to be more common toward the end of the primary affection than during the period of its greatest virulence. He explains this very properly on the ground that Avhen the discharge is great much care is used in cleansing the fingers. It is after the discharge has become scant that patients become careless. The right eye is usually the one first affected, because most patients are right-handed.

Ilis experiments proved that the generally accepted view that the transference to the eye of gonorrhceal pus results in a simple conjunctivitis or a mild purulent ophthalmia, and only rarely in a severe inflammation, is false. On the contrary, he asserts that the result is always a purulent ophthalmia of a severe degree. The only exception occurs in those cases in ■which early treatment is successfully applied.

The contagious character of the secretion of ophthalmia neonatorum had been looked upon as ridiculous ;* when .Tuengken stated that a ni;rse had developed severe i)urulent ophthalmia during the night of the same day when she had infected them with a sponge that had been used to cleanse the eyes of an infant with ophthalmia, it was laughed at. No one can deny the infection in his own cases, because the material was carried across the street into another house and yet the result was always the same.

His experiments on the production of purulent ophthalmia embrace almost one hundred eyes, and this does not include a number of accidental infections which were observed with the same care. The matter with which infection was produced was obtained from eyes afl'ected with different forms of purulent ophthalmia as well as from genital blennorrhcea. All ages and both sexes were found to be equally predisposed.

One of the most interesting chapters is the one on the character of the blennorrhceic contagion. Though the pus from the conjunctiva causes infection when applied to the eyes of human beings, he was unable to produce any result when he applied it to the eyes of such animals as dogs, cats, hogs, and various birds. Others had claimed that they had produced effects in such cases. Our jiresent knowledge of the immunity of animals to gonorrhcea shows that Piringer was not deceived.

The granulation from which the pus is secreted carries the contagious property with it, as was shown in 1833 by Werwick, who experimented upon two nurses. Piringer never made any experiments w'ith granulations because it lacked any practical bearing.


  • The faith with which this opinion has been held can be measured by the much-quoted citation of Dr. Vetch, referreil to above.

Piringer likewise ciuotes Adams, who rubbed his eyes with a finger smeared with purulent matter without producing ill results, as did Van Sevenoeck and Kriebel. Morburgo smeared the eyes of 300 soldiers without effect.


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The pure lachrymal fluid of a blennorrhoeic eye was found not to possess conhigioiis properties. An experiment is related in which lachrymal fluid collected upon a canielliair brush did not produce infection, while the purulent secretion gathered a few days later did.

The question of contagion far distance (per miasma) was studied in his hospital, where numerous blennorrhceic patients were placed beside those unaffected, in small wards. He was able to prove definitely that such contagion does not occur and that the cases in which it is suspected can always be traced to direct infection.

The vapor of drying secretion has no power of infection. Even those secretions which are perfectly serous leave a residue when evaporated, and it is this which still retains the contagious {)roperties.

The fluid secretion when kept for three or four days, even without evaporation, is no longer contagious.

If a finger is covered with blennorrhceic secretion and washed immediately in clear fresh water and well dried, it will cause no infection if rubbed over the conjunctiva.

Blennorrhoeic matter may be smeared over the eyelids if the palpebral fissure is kept firmly closed by adhesive plaster, and no infection will occur. In order to produce infection the secretion must reach the conjunctiva.

The secretion of acute blennorrhoea of a moderate degree is just as contagious as that of the most severe. Such pus is capable of producing infection even when diluted with 50 or 100 parts of water. The pus of a very mild purulent ophthalmia and of chronic ophthalmia has much less power of infection.

As long as there is any secretion in any case of purulent ophthalmia, whether mild or severe, so long the case is contagious. Wiien the secretion ceases, tiiough there maybe considerable congestion and photophobia, the infectious properties are lost.

The properties of infection inherent in the secretion do not vary in different seasons of the year nor under changed atmospheric condition, whether exposed to the glare of the sun or to the cold of the winter. Experiments .to determine this may appear meaningless to us, but we must not forget the opinions prevalent in Piringer's time.

Numerous experiments were made to determine the effect upon the contagious properties of the pus when separated for varying intervals of time from the human body. Thus the secretion was collected upon a camel-hair brush and allowed to become as dry as possible (" dry as glass ") in from three to six hours. If then applied to the conjunctival sac, but not allowed to soften in the tears, no infection occurred ; if softened in the tears, or previously in water, infection was sure to occur.

In seven cases the secretion which had been allowed to dry for thirty-six or forty hours in the open air had lost all contagious property, but in two in which the secretion had been allowed to get dry thirty- three or thirty-four hours in the room and was then softened it produced very severe ophthalmia blennorrhcea. Piecesof linen smeared with fresh blennorrhceic matter and given to a pannus patient to wipe his eyes produced infection, but if the cloth had been dried in the air for several days, the patient could use it about the eyes witiiout harm, and the


secretion when scraped off" the cloth and inserted into the conjunctival sac produced infection only when it was less than thirty-six hours old. On the other hand, if the secretion was placed in a vaccine case and hermetically sealed it retained its contagious property for forty-eight hours, but lost it entirely when kept for three days. The pus fioma case of ophthalmia neonatorum produced infection when kept in this way for two and a half days. Piringer therefore concludes that "?/Ze««orrJiieic pus loses its contagious properties as it hecornes older, and (jraduaUy dies in from twenty-six to forty -eight hours, jjossessing no more organic life token three days have passed." It is upon the discovery of this fact that Piringer bases important rules of prophylaxis, and explains the relative infrccjnency of gonorrhoeal ojDhthalmia among the common people.

Piringer studied carefully the length of time intervening between the entrance of the infectious material and the first signs of the developing disease, the period of incubation. This he found to vary according to the manner and the amount of the infection, as well as according to the individual peculiarity of the patient. The higher the degree of inflammation, the more rapidly did its pus infect. Thus the pus from a very severe ophthalmia produced infection in from six to twelve hours, or at most in thirty-six hours ; while that of very mild blennorrhoea might rec|uire sixty to seventy hours, and that of a case of chronic blennorrhcea seventy-two to ninety-six hours.

The secretion of the second stage of acute ophthalmia acts more slowly than that of the first; thus the pus from a case of very acute blenuorrhrea in which the secretion was markedly diminishing may take sixty hours to produce the first symptoms.

If the secretion while still warm is immediately transferred from an acute blennorrhcea, but six or eight hours are required for the first signs to show themselves, and in twelve or eighteen hours the disease is fully developed. In this respect the conjunctiva responds more rapidly than the genital mucous membrane. The longer the secretion is kept before it is placed in the conjunctiva, the less rapidly does it act. The rapidity likewise varies with the amount of secretion brought into the eye.

Piringer gave the prophylaxis of gonorrheal ophthalmia his careful attention and the results were very important. Can tiie inflammation be aborted after the infectious material has once reached the conjunctiva? Several cases in which the very early and continued application of ice comitresses produces this effect are described. In order to determine whether the infectious material can be removed and the outbreak of the disease prevented, several series of experiments were made. The method which required the application of very strong solutions of bichloride of mercury, concentrated acetic acid, etc., appeared to him too severe, and in the few cases in which it was tried the desired result was not obtained.

On the otiier hand he found that washing out the eye with water after the contagious material had been inserted prevented the development of the disease, provided that it is done sufficiently early. These experiments were made on three patients. In the first case he touched the eye with a large quantity of matter from a newborn babe, cleaned it out after a minute with a sponge dipped in cold water, and had cold water apiilicatioMs made for ten hours. No inflammation resulted.


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Four days later he varied the experiment by allowing the matter to remain two minutes and again no inflammation occurred. After another interval of four days the experiment was again repeated, the pus remaining in the eye for three minutes and the result was again the same. After another interval of 6ve days pus was inserted and allowed to remain in the eye for live minutes; no cold applications were made; the result was a violent inflammation. This patient had pannus, which was cured by the treatment.

In order to try tiiese experiments upon a perfectly normal conjunctiva he selected the eyes of an amaurotic beggar whom he paid for these privileges. In this case he found that no disease resulted if the blennorrhoeic matter was washed out within three minutes after its entrance into the conjunctival sac and cold water applied. In three minutes any one who has accidentally infected his eyes can obtain fresh water with which to wash them !

In order to determine whether the washing out of the conjunctival sac would accomplish the same result without the use of ice applications, he infected the eye of a girl suffering with pannus with blennorrhoeic matter and washed out the conjunctiva in three minutes. Ninety hours later a severe ophthalmia developed. And in a second case the experiment again resulted in the development of a purulent ophthalmia, but not until the fifth day, and in this case the ophthalmia was of a milder character. For these reasons he considers the cold water application as essential to the prevention of conjunctival blennorrhci'a after infection has occurred. Many other questions are considered by Piringer, but this review embraces the essential points, and will, I trust, suffice to show its importance.

The care, the true scientific spirit, the accuracy of observation and experiment, the unbiased search for truth, form marked characteristics of I'iringer's work. And yet he is so modest as not to claim that his results are "the absolute truth," though they are his own firm convictions; experiments and observations, he tells us, by other physicians at other times and places, made with care and without prejudice.


are needed to confirm them as well as to clear away any errors. His experiments were arranged carefully and judiciously to determine the character and the attributes of the contagion, the time during which it acted, the gradual diminution of its powers to the point when they were entirely lost, the intensity of the contagion, and the degrees of dilution which could be borne without loss of all contagious properties. Many of these questions were given their final solution by Piringer. He separated the fluid portions of the pus which could be evaporated, from the more solid matter which contained the contagious quality. He proved that the unknown cause of contagion was a something which had to be transferred in substance from one mucous membrane to the other, and which never acted at a distance, thus disproving the old miasmatic principles which were still current in those days.

In what is our knowledge today greater than that of Piringer, excepting that the active agent, the living microorganism, the gonococcus, has been discovered, a discovery only made in 1879 ? That it was a living organism even Piringer surmised, for, as we read above, he speaks of it as "growing older," and "dying," and "possessing organic life." Let us not forget when it was that Piringer worked. Though micro-organisms had been discovered toward the end of the seventeenth century, and micro-organisms were assigned as the causes of numerous diseases during the eighteenth century, it was not until 1840 that Henle first established the germ theory of disease upon the solid foundation of logic and fact.

One aspect of Piringer's experiments still deserves mention. Others had likewise made experiments with a view of transferring the disease which we have been considering; but most of these were unsystematic, few in number, and led only to confusion. Piringer's work was such as to give a definite solution to important questions, results which have stood the tests of time. His work was not in vain. His hopes were fulfilled that "the medical world would read not entirely without pleasure a number of results, whose collection in the field of practice had been made at the cost of much strain, great pains and many a sleepless night."


PROCEEDINGS OF SOCIETIES


THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY.

Meeting of May 3, 1897.

Dr. Thayer in the Chair.

Haeniatoniyelia from (xunshot Wonnd of tlie Cervical Spine.— Dr. CiisniNG.

This patient, a young woman of 27 years, was brought into Prof. Ilalsted's service, November Gth, 1896, with the hiotory of having been shot twice in the neck a few hours before entrance. Our chief interest centres in the injury produced by the missile, whose wound of enti-ance is situated here on the right side of the neck at the level of the cricoid cartilage. These skiagraphs show the point of lodgment of the bullet in the centrum of the sixth cervical vertebra.

The case illustrates some unusual features of one type of


the so-called Brown-Seqnard paralysis; the value of the X-rays in locating the offending missile; a practical recovery without operative interference; a residuum of symptoms resembling those of syringomyelia.

At entrance she was suffering from agonizing " pains " of a " pins and needles " character, especially in the arms, so severe she would cry out when they were touched. No radiating pains, such as are described iu the meningeal form of hemorrhage, were present. There had been no loss of consciousness. Motor paralysis was complete on the right side below the level of Thorburn's "5th root group." On the left there was a brachial monoplegia up to this same segmental level, namely that for the deltoid biceps and supinator longus muscles whose ventral horn ganglion cells lie in the 5th cervical segment, as you may see by comparison with this


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[Nos. 77-78.


familiar table of Starr's. Respiration was purely diaphragmatic.

On the left side, uji to the second intercostal space and down the ulnar side of the arm over an area which corresponds, as these diagrams taken from Starr and Kocher demonstrate, to the cutaneous sensory fields of the eighth cervical and first dorsal segments, there existed anassthesia to pain and thermic stimuli, aud a slight dulling of tactile or pressure sensibility. A segmental zone of similar anaesthesia was present on the side of motor paralysis across the chest aud including most of the right arm.

There was a marked elevation of surface temperature, cousiderable hyperalgesia, and also a diminution of reflex activity on the paralyzed side. Loss of sphincteric control over the contents of the bladder aud rectum was also jjresent.

liestitution from these paralytic symptoms has taken place up to the excellent conditiou in which you see the patient at present. The motor paralysis disapjjeared gradually. On the tenth day, motion, as is usual, was first observed in a slight flexion of the thigh. Turner in his experimental work called attention to this. At the present time there remains evidence of the degeneration of the right j)yramidal tract iu Wernicke's residuary paralysis of the dorsal flexors of the foot, giving the late hemiplegic character to the jjatient's gait. Mann has recently called attention to this residuum of motor paralysis aud has shown that it selects a certain muscle unit (bewegung einheit), this unit being that which lifts and shortens the leg in the first stage of walking, as can be demonstrated in this patient. Paralysis remains alone complete in some of the small muscles of the right hand, representing destruction of ganglion cells at the site of the lesion. There is au exaggeration of all the deep reflexes of both extremities. Myotatic contractions, as you see, are elicited iu the muscles of the right arm by gentle blows on the tendons. Resolution of the sensory disturbances has been less complete. Slight anEesthesia to painful aud especially thermic stimuli persists on the left.

A month ago there was present a peculiar distribution of areas of hyperesthesia, over which cold produced paiu without thermic sense, and the threshold for pain was so low to touch or pressure stimuli that the latter could only be elicited with difficulty by v. Frey's assthesiometer. This is illustrated by these diagrams.

The lesion was presumably due, as in Mann's case, to an intramedullary hemorrhage, the occurrence of which, especially in the cervical enlargement, as emphasized by Thorburn, is not uncommon. It seems that not only is traumatic hajmatomyelia much more common here than elsewhere in the cord, but that there is a certain level iu this enlargement giving symptoms corresponding to the "typus inferior" of Krause, iu which intramedullary hemorrhage is most likely to occur. This list of cases, collected from the literature, tends to confirm this view of a site of predilection in the lower cervical enlargement for hajmatomyelia, and illustrates the fact that not only in cases attributable to acute flexions of the neck does it occur, as was believed by Thorburn, but also iu those due to a great variety of traumatic causes. The hemorrhage also is apt to occur most extensively on one side of the


cord, thus often producing the symptom complex of a Brown Sequard type of paralysis.

That the hemorrhage also in these cases selects by preference the gray matter of the cord, presumably from the greater vascularity aud less support given to the vessels there, is well recognized. Frequent note has also been made of cavity formation at the original nidus of hemorrhage, which is interesting iu consideration of the association of the syndrome of syringomyelia which Minor and others have pointed out to be a common sequence of traumatic ha'matomyelia and which persists in this patient.

The case which Maun has recently reported in full with post-mortem examination of the cord, in the Dent. Zeit. f. Nervenheil. for 1896, and which clinically bears such close similarity to this case, illustrates many of these points very completely.

Dr. Thomas. — This case seems to me to be one of particular interest, aud the Society is to be congratulated on having it so admirably presented. Those of you who have had the opportunity of examining a similar case will recognize the difficulty of making such au exhaustive examination. I know of no case in the hospital records that has been worked up so carefully as this. Dr. Gushing was kind enough to bring the patient to me ou several occasions for examination, and I confirmed the results which he had already obtained. The patient's condition, after she had been in the hospital for some time, was, as Dr. Gushing has described to you, briefly as follows : there was weakness of the right leg and right arm. The muscles of the right arm were atrophied, aud there were sensory disturbances, as shown in the charts. The wound in the right side of the neck was in such a position that the bullet might have injured the brachial plexus before entering the spinal columu, and thus have produced the condition found in the right arm. An electrical examination of tlie paralysed and atrophied muscles showed that they responded normally to the currents. This was believed to indicate that the brachial plexus was not injured, aud also that the paralysis was not due to destruction of the anterior horns from which the nerves forming this plexus arise. I do not believe that there can be extensive destruction of the anterior horns without the occurrence of degenerative atrophy of those muscles which receive their nerves from that segment of the cord. In the case of Maun, to which Dr. Gushing has referred, there was paralysis and atrophy of the muscles of the left arm. This was completely recovered from, but, at the autopsy, a lesion iu corresponding anterior horn was found. This case is, as far as I know, the only one bearing on this poiut, and it does not seem to me to be conclusive. The lesion was limited to the eighth cervical segment, as shown by the fact that the eighth root was degenerated, while the seventh was not, and the first thoracic root was only slightly so. We know that each muscle is represented in more than one spinal segment, and it can be understood how a limited lesion in one segment need not necessarily produce degenerative atrophy to such a degree that it could be discovered during life. The autopsy on Mann's case was incomplete, in that neither the muscles nor the peripheral nerves were examined.

Dr. Cushing's case is of interest from so many standpoints


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that it is impossible to discuss it fully. Unilateral lesions of the cord are not very common. In the dispensary we have the records of only two typical cases. I have at present under observation a very beautiful example of this form of paralysis. The patient is a woman whose right leg is paralysed and who shows the disturbances of sensation in the left leg which Mann has pointed out as characteristic, i. e. the sensory conduction for touch is undisturbed, whereas pain, heat and cold stimuli do not produce their normal effect. The paths of sensory conduction within the cord have been and are the subject of much discussion. Of late the anatomists and physiologists have been inclined to the view that the paths do not cross, but remain on the same side of the cord until they reach the medulla. Clinicians, on the other hand, from the study of the cases of unilateral lesion of the spinal cord, have held to the belief that the sensory jiaths decussate soon after entering the spinal cord. That there must be an anatomical basis for the constant occurrence of the classical symptoms of Brown-Sequard's paralysis seems to me to be self-evident. The burden of jiroof must rest ujiou the anatomists and physiologists.


NOTES ON NEW BOOKS.

Diseases of the Rectum, Anus and Contiguous Textures. By S. G. Gant, M. D. (Philadelphia : F. A. Davis, 1896.)

With the exception of two chapters on Cancer of the Rectum and Colotomy by Allingliam, a recognized authority on these subjects, the worls of Dr. Gant is not to be commended. The booli contains nothing new, and there are many superior works on this subject. The two cliapters in which the author seems to talce special pride, one on auto-infection, tlie other on effects of railroading on diseases of the rectum, are not remarkable, and the first is unsatisfactory. That employes of railroads suffer much from constipation and hemorrhoids as a result of their occupation may be true, but the figures he gives can be handled in many ways. If we eliminate from the author's statistics all cases suffering from these two very common conditions, we have less than 1 per cent, out of over 170,000 cases seen in various hospitals suffering from other diseases of the rectum and anus; and 5.7 per cent, in the same number of cases does not seem to us an excessive number to be suffering from the two conditions mentioned. We believe that among the poor laboring class constipation is the usual condition found, and that figures more striking than these could easily be collected to show that constipation was one of the commonest symptoms in all hospital cases. We question whether the jarring of a railroad train will continually rock a stomach from side to side, produce a "sea-sick stomach," or whether it is suiEcient to bring about by itself dilatation of the veins about the anus and rectum by causing a venous stasis, and we know that swelling of the feet in railroad travelers is not an ordinary condition, to say the least. The chapter on sodomy might better have been omitted or much abbreviated ; such a book does not call for a psychological explanation of this practice. In speaking of the relation of pulmonary tuberculosis to fistula, the author states : "So we meet with two kinds of tubercular fistula — one as a result of localized tubercular ulceration with or without any lung complication ; the other a fistula in persons who have lung trouble, due to the absorption of fat about the iscliia, general debility, and abscess. In the feces of the first variety can be found the tubercle bacilli of Koch, while in the second variety they cannot be found unless the sputum containing them has been swallowed, and gastric digestion has been impaired to such an e.Ntent as not to destroy them or their spores." In either form the fistula is tubercular and the bacilli


can be found without these coming from the sputum ; and gastric digestion, even when normal, does not ordinarily destroy them, as we know from the large number of cases of primary intestinal tuberculosis which occur. We do not think that the following statements as regards auto-infection are true. On p. 271 we read : " Our Creator, however, foresaw all dangers and provided us abundantly with safeguards with which we can destroy or neutralize the poisons on the one hand, or throw them off on the other, as soon as they are formed"; and on p. 272, "Just so long, however, as the emunctories are working in harmony and perform their individual functions, and there is no lesion of the intestinal mucosa, all is well, and all poisons, no matter whether theyare the products of decomposition or of bacterial action, will do noharm, forthe reason that they are thrown into a special reservoir (the liver) where they are destroyed or neutralized and afterward discharged from the body."

The colored illustrations in this work are hideous and unnatural, and the woodcuts are not models of artistic excellence. Would it not be well for authors to cease to reproduce cuts of the most common and onlinary instruments, and of well-known positions and procedures in operations, which are quite valueless (cf. cuts on pp. 20, 21, 22, 25, 218,219, 220). Wedislike extremely to see theauthor's autograph on the outside cover, and the long list of societies to which he belongs following his name on the title-page. If the book possesses merit of its own, this sort of cheap advertisement does it no good ; and it does not help the work in any case.


BOOKS RECEIVED.

Second CtUalogne of the Library of the Peabody Institute of the City of Baltimore. Including theadditions made sinceI882. Parts I-II. A— D. 1890-97. 4to. Baltimore.

The Semi-Centennial of Anmsthesia. October 16, 1846-October 16 1896. 4to, 95 pages. 1897. Massachusetts General Hospital, Boston.

Saint Bartholomeio' s Hospital Reports. Edited by S. West, M. D., and W. J. Walsham, F. R. C. S. 1896. Vol. XXXII. 8vo, 518 '+ 197 pages. 1897. Smith, Elder & C >., London.

Transactions of the American Pediatric Society. Eighth session held in Montreal, Canada, May 25, 26 and 27, 1896. Edited by Floyd M. Crandall, M. D. Vol. VIII. 1896. 8vo, 243 pages. Reprinted from the Archives of Pediatrics. New York.

Medical and Surpical Reports of the Boston City Hospital. Eighth Series. Edited by G. B. Shattuck, M. D , W. T. Councilman, M. D., and H. L. Burrell, M. D. 1897. 8vo, 391 pages. Published by the Trustees, Boston.

King's College Hospital Rejiorts. Being the annual report of King's College Hospital and the medical department of King's College. Edited by N. Tirard, M. D., F. R. C. P., et al. Vol. III. (Oct. 1st, 1895-Sept. 30th, 1896.) 8vo. 1897. 332 pp. Printed by Adlard & Son, London.

Twentieth Century Practice. An international encyclopedia of modern medical science by leading authorities of Europe and America. Edited by T. L. Stedman, M. D. In twenty volumes. Vol. XI: Diseases of the Nervous System. 8vo. 1897. 962 pp. William Wood &, Co., New York.

Burdett's Hospitals and Charities, 1897. Being the year-book of philanthropy. By Henry C. Burdett. 12mo. 1897. 1018 pages. The Scientific Press, London.

Archives of Skiagraphy. Edited by Sydney Rowland, B. A., Camb. Fol. Vol. I, No. 4. April, 1897. The Rebman PublishingCo., Limited, London.

A Pictorial Atlas of Skin Diseases and Syphilitic Affections in PhotoLithochromes from Models in the Museum of the Saint Louis Hospital, Paris. With explanatory woodcuts and text by E. Besnier, A. Fournier et al. Edited and annotated by J. J. Pringle, M.B., F. R. C. P. Part X, 1897. W. B. Saunders, Philadelphia.


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[Nos. 77-78.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS. Volume I. 423 pages, 99 plates.

Reiiort in Patbologry.

The Vessels and Walls of the Dog's Stomach; A Study of the Intestinal Contraction;

Healing of Intestinal Sutures; Reversal of the Intestine; The Contraction of the

Vena Portae and its Influence upon the Circulation. By F. P. Mall, M. D. A Contribution to the Pathology of the Gelatinous Type of Cerebellar Sclerosis

(Atrophy). By Henry J. Berklev, M. D. Reticulated Tissue and its Relation to the Connective Tissue Fibrils. By F. P.

MiLL, M. D.

Report in Derniatolos-y. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and other Organs. By

T. C. Gilchrist, M. U., and Emmet Rixford, M. D. A Case of Blastomycetic Dermatitis in Man; Comparisons of the Two Varieties of

Protozoa, and the Blastomyces found in the preceding Cases, with the so-called

Parasites found in Various Lesions of the Skin, etc. ; Two Cases of MoUuscum

Fihrosum; The Pathology of a Case of Dermatitis Herpetiformis (Duliring). By

T. C. Gilchrist, M. D.

Report in Patliology. An E.xperiniental Study of the Thyroid Gland of Dogs, with especial consideration

of Hypertrophy of this Gland. By W. S. Halsted, M. D.


Volume II. 570 pages, with 28 plates and figures.

Report in Medicine.

On Fever of Hepatic Origin, particularly the Intermittent Pyrexia associated with

Gallstones. By William Osler, M. D. Some Remarks on Anomalies of the Uvula. By John N. Mackenzie, M. D. On Pyrodin. By H. A. Lafleur, M. D. Cases of Postfebrile Insanity. By William Osler, M. D. Acute Tuberculosis in an Infant of Four Months. By Harry TonLUIN, M. D. Rare Forms of Cardiac Thrombi. By William Osler, M. D. Notes on Endocarditis in Phthisis. By William Osler, M. D.

Report in ftleilieine. Tubercular Peritonitis. By William Oslek, M. D. A Case of Raynaud's Disease. By H. M. Thomas, M. D. Acute Nephritis in Typhoid Fever. By William Osler, M. D.

Report in Gynecology. The Gynecological Operating Room. By Howard A. Kelly, M. D. The Laparotomies performed from October 16, 1889, to March 3, 1890. By Howard

A. Kelly, M. D., and Hunter Robb, M. D. The Report of the Autopsies in Two Cases Dying in the Gynecological Wards without Operation; Composite Temperature and Pulse Charts of Forty Cases of

Abdominal Section. By Howard A. Kelly, M. D. The Management of the Drainage Tube in Abdominal Section. By Hunter Robb,

M. D. The Gonococcus in Pyosalpinx; Tuberculosis of the Fallopian Tubes and Peritoneum;

Ovarian Tumor; General Gynecological Operations from October 15, 1889, to

March 4, 1890. By Howard A. Kelly, M. D. Report of the Urinary Examination of Ninety-one Gj-nccological Cases. By Howaed

A. Kelly, M. D., and Albert A. Ghbiskey, M. D. Ligature of the Trunks of the Uterine and Ovarian Arteries as a Means of (decking

Hemorrhage from the Uterus, etc. By Howard A. Kelly, M. D. Carcinoma of the Cervix Uteri in the Negress. By J. W. Williams, M. D. Elephantiasis of the Clitoris. By Howard A. Kelly, M. D. Myxo-Sarcoraa of the Clitoris. By Hunter Robb, M. D. Kolpo-Ureterotomy. Incision of tlie Ureter through the Vagina, for the treatment

of Ureteral Stricture; Record of Deaths following Gynecological Operations. By

Howard A. Kelly, M. D.

Report in Snrgery, I. The Treatment of Wounds with Especial Reference to the V.-ilue of the Ulocid Clul

in the Management of Dead Spaces. By W. S. Halsted, M. D. Report in Neurology, I. A Case of Chorea Insaniens. By Henry J. Berkley, M. D. Acute Angio-Neurotic Oedema. By Charles E. Simon, M. D. Ilaeniatomyelia. Bv August Hoch, M. D. A Case of Cerebro-Spinal Syphilis, with an unusual Lesion in the Spinal Cord. By

Henky M. Thomas, M. D.

Report in Fntliology, I. Amoebic Dysentery. By William T. Councilman, M. D., and Henri A. Lafleue, M. D.


Volume III. 766 pages, with 69 plates and figures.

Report in PatUology.

Papillomatous Tumors of the Ovary. By J. Whitridge Williams, M. D.


Tuberculoais of the Female Generative Organs. By J. Whitridge Williams, M. D. Report in Pjitliology.

Multiple Lympho-Sarcomata, with a report of Two Cases. By Simon Flexner, M. D.

The Cerebellar Cortex of the Dog. By Henry J. Berkley, M. D.

A Case of Chronic Nephritis in a Cow. By W. T. Councilman, M. D.

Bacteria in their Relation to Vegetable Tissue. By H. L. Russell, Ph. D.

Heart Hypertrophy. By Wm. T. Howard, Jr., M. D.

Report in Gynecology.

The Gynecological Operating Room; An External Direct Method of Measuring tlie Conjugdta Vera; Prolapsus Uteri without Diverticulum and with Anterior Knterocele; Lipoma of the Labium Majus; Deviations of the Rectum and Sigmoid Flexure associated with Constipation a Source of Error in Gynecological Diagnosis; Operation for the Suspension of the Retroflexcd Uterus. By Howard A. Kelly, M. D.

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 A. L. Stavely, M. D.


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

Tabulated by A. L. Stavely, M. D. The Employment of an Artificial Retroposition of the Uterus in covering Extensive

Denuded Areas about the Pelvic Floor; Some Sources of Hemorrhage in Abdominal Pelvic Operations. By Howard A. Kelly, M. D. Photography applied to Surgery. By A. S. Murray. Traumatic Atresia of the Vagina with Hsematokolpos and Hxmatometra. By Howa&d

A. Kelly, M. D. Urinalysis in Gynecology. By W. W. Russell, M. D. The Importance of employing Anesthesia in the Diagnosis of Intra-Pelvic Gj-neco logical Conditions. By Hunter Robb, M. D. Resuscitation in Chloroform Asphyxia. By Howard A. Kelly, M. D, One Hundred Cases of Ovariotomy performed on Women over Seventy Years of Age.

By Howard A. Kelly, M. D., and Mary Sherwood, M. D. .\bdominal Operations performed in the Gynecological Department, from March 6,

1890, to December 17, 1892. By Howard A. Kelly, M. D. Record of Deatlis occurring in the Gynecological Department from June 6, 1890, to

May 4, 1892.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typliold Fever.

By William Osler, M. D., with additional papers by W. S. Thayer, M. D., and J. Hewetson, M. D.

Report in Pfenrology, Dementia Paralytica in the Negro Race; Studies in the Histology of the Liver; The Intrinsic Pulmonary Nerves in Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of J/us musculu^; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berkley, M. D.

Report in Surgery. The Results of Operations for the Cure of Cancer of the Breast, from June, 1889, to January, 1891. By W. S. Halsted, M. D.

Report in Gynecology. Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cullen, M. B. Report in Patliology. Deciduoma Malignum. By J. Whitridge Williams, M. D.


Volume V. 480 pages, with 32 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J. Hewetson, M. D. A Study of seme Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typhoid Fever. By William Osler, M. D., with additional papers by G. Blumer, SI. D., Simon Flexner, M. D., Walter Reed, M. D., and H. C. Parsons, >I. D.


A'olume VI. 414 pajif.s, with 7') plates and figures.

Report in Neurology.

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Introductory.— Recent Literature on the Pathology of Diseases of the Brain by the Chromate of Silver Methods; Part I. — Alcohol Poisoning. — Experimental Lesions produced by Chronic Alcoholic Poisoning (Ethyl Alcohol). 2. Experimental Lesions produced by Acute Alcoholic Poisoning (l^thyl Alcohol) ; Part II. — Serum Poisoning. — Experimental Lesions induced by the Action of the Dog's Scrum on the Cortical Nerve Cell; Part HI. — Ricin Poisoning.— Experimental Lesions Induced by Acute Ricin Poisoning. 2. Experimental Lesions induced by CJhronic Ricin Poisoning; Part IV.— Hydrophobic Toxaemia. — Lesions of the Cortical Nerve Cell produced by the Toxine of Experimental Rabies; Part V. — Pathological Alterations in the Nuclei and Nucleoli of Nerve Cells from tlie Effects of Alcohol and Ricin Intoxication; Ner\-e Fibre Terminal Apparatus; .^sthenic Bulbar Paralysis. By Henry J. Berkley, M. D.

Report in Patliology.

Fatal Puerperal Sepsis due to the Introduction of an Elm Tent. By Thomas S.

(3lTLLEN, M. B. Pregnancy in a Rudimentary Uterine Horn. Rupture, Death, Probable Migration of

Ovum and Spermatozoa. By Thomas S. Cullen, M. B., and G. L. WiLSlNS, M. D. Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. Cullen, JI. B. A Bacteriological and Anatomical Study of the Summer Diarrhoeas of Infants. By

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BULLETIN


OF


THE JOHNS HOPKINS HOSPITAL.


Vol. Vlll.-No. 79.]


BALTIMORE, OCTOBER, 1897.


[Price, 15 Cents.


COlsTTIElNrTS.


A Second Series of Cataract Operations (One Hundred and

Fifty-eight). By Robert L. Randolph, M. D., . . Parotitis following Visceral Inflammation. — A Report of Two

Cases. By A. Duval Atkinson, M. D.,

Palpation of the Foetal Heart Impulse in Pregnancy. By

Douglas F. Duval, M. D.,

Squamous Epithelioma in a Dermoid of the Jaw. By S. M.

Cone, M. D.,

The Infectiousness of Chronic Urethritis. By E. R. Owings,

M. D., . .


The Importance of employing Pure Salts in the Preparation of the Schott Bath. [Communication.] By C. N. B. Camac, M. D., 214

Proceedings of Societies :

Hospital Medical Society, 215

Demonstration of a Case. Probable Brain Tumor [Dr. Thomas] ; — Demonstration of Specimens [Dr. Cullen].

Notes on New Books, 218


A SECOND SERIES OF CATARACT OPERATIONS (ONE HUNDRED AND FIFTY-EIGHT).*

By Egbert L. Randolph, M. D.


Five years ago I reported in the Bulletin of the Johns Hopkins Hospital a series of fifty consecutive cataract operations. Of these fifty operations six were performed in a hospital. With the exception of eighteen, the remaining twentysix were among the poorer classes of a country population in Virginia and in a mining region in the western part of Maryland. This series then is chiefly interesting from the rather unusual conditions which surrounded most of the patients. For instance, the first case reported (Series I, Case 1) was operated on in a log cabin near Warrenton, Va., and the old man was nursed by his daughter, who saw him only at meal times and at night (she being in service), and as a consequence he was exposed not infrequently to risks during her absence. He went through the same experience a year later with his other eye and, as in the first instance, obtained excellent vision. Case 8 (in the same series) had been blind for three years and lived at a remote point on a plantation in Virginia, and he was nursed by his wife. His cabin was too dark for the operation and I put him on a cot and operated out in the yard. He was very timid and jumped when the iridectomy was performed, causing some loss of vitreous. He counted my fingers after the operation and I assisted him upstairs to a room next


  • Read at the annual meeting of the American Ophthalmological

Society, AVashington, D. C, May, 1897.


to the roof, as the only other room in the house opened out into the yard. He remained there for a week, and at the end of that time was allowed to come downstairs. He subsequently obtained perfect vision. Case 39 (Series I) was operated on in a cabin full of negro children, and he was looked after by his daughter. The result was most satisfactory. In this series of fifty, two failed to recover sight, and as the circumstances peculiar to these were rather unusual and as such might explain the failure, I shall relate the histories. Case 49, woman 78 years old, had been troubled many years with dacryocystitis, more marked in the left eye than in the right. She had been blind from cataract for three years. Refused treatment for the lachrymal trouble, saying she was too weak and old to stand the pain incident itpou the probing. She was made acquainted with the additional risk of a cataract operation performed on an eye where there was disease of the lachrymal sac. She was willing, however, to run the risk of infection from this source, so I operated on the least affected eye. The result was a perfect success. A year later she presented herself for operation upon the second eye. The operation was smooth and she counted fingers with ease immediately afterward. I left the city that evening, not expecting to see her again for two weeks. She was entrusted to the care of the physician who assisted me in the operation. It is well to state here that she belonged to a most ignorant class of white


200


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 79.


people, and though nearly eighty years of age, was accustomed to going barefooted in tvarm weather. The first time I operated she had shown herself unmanageable and walked around the house three days after the operation. That was in the winter time. The second operation was in June last, and when I saw the patient two weeks after the operation her physician told me that she got up out of bed the next day, tore the plaster off her good eye and came downstairs and sat in the yard and smoked her pipe. The second day after the operation she walked nearly a mile barefooted to see her daughter. Whatever were the causes which produced it, when I saw her the second time the eye was lost. It is impossible, then, to say whether to attribute the loss of the eye to infection from the mucocele or to carelessness and exposure after the operation. Before each operation the contents of the lachrymal sac were pressed out, and, as far as possible, the conjunctival sac was rendered aseptic by irrigating it with a solution of corrosive sublimate t^^jtj-.

The second case (Case No. 47) is that of a man sixty-one years old. He had been subject for many years to rheumatism, and had suffered also for a long time with varicose veins on both legs, and as a result of the latter condition his right leg was covered with an eczema. The blood-vessels at his wrists and temples were tortuous and hard. Left eye, total cataract and good field of vision for light. The operation was absolutely smooth, and after the delivery of the lens the patient could see my face and count fingers readily. I removed the speculum and closed the eye, putting on the usual bandage. Ten minutes later, and just before I was about to leave the house, he complained of violent pain in the eye. I suspected hemorrhage and immediately removed the bandage to investigate. I found the latter soaked with blood. The mass of blood and protruding vitreous were cleaned away and strong pressure applied. On returning six hours later it was found that the oozing had continued and he was still suffering pain. The lids were opened and a clot of vitreous was discovered between the edges of the wound. This was removed, and after first irrigating the conjunctival sac with a very weak sublimate solution, a pressure bandage was applied. At my visit the next day I found the bandage quite moist and there was every evidence that the oozing was persisting. I cleaned out the sac again and renewed the bandage. On the afternoon of the second day I saw him again and there were still signs of hemorrhage. The same course of treatment was pursued and on the third day I found the bandage clean. Of course he was told that vision was irrevocably gone from the onset of the hemorrhage. In nearly all cases of this class the cornea sloughs, but this termination I fortunately escaped. Hemorrhage after cataract extraction is rare. Dr. Knapp reports in a recent number of the Archives of Ophthalmology his only case. In my own case I can account for the hemorrhage only by the condition of the blood-vessels throughout his body. ,v, No doubt the vessels of the retina were tortuous and their walls atheromatous, and when the lens was removed and intraocular tension thereby lowered, the blood-vessel walls could not withstand the pressure from the increased volume of blood pouring into them; so they ruptured. The whole condition of


the patient pointed to a diseased state of the circulatory apparatus. It is impossible to guard against such a termination, though I should regard it as a contra-indication for operation upon the other eye, for no matter how smooth the operation might be, the chances are that hemorrhage would follow the delivery of the lens.

Out of this series, then, all obtained useful vision but Cases 47 and 49.

Since the publication of this series I have operated upon 158* cases and the tabular statement is herewith appended. Two of the cases are especially interesting as being instances of maniacal excitement, possibly due to the use of atropine after the operation. The first case was a colored man, operated upon in the poorhouse of Mineral Co., W. Va. He was seventy-five years old and had been practically helpless from cataract for a year. Atropine was instilled immediately after the operation. The next morning the physician. Dr. C. S. Hoifman of Keyser, W. Va., was sent for and he wrote me that the patient had gotten up during the night, torn the bandage off, secured a razor from one of the inmates of the room and had gashed his throat in several places and was bleeding profusely when found. In the excitement which followed the eye was forgotten and it was some time before the bandage was replaced. He was quieted, and seven days later, that is, on the eighth day after the operation, he disappeared from the jDOorhouse and two mouths afterward was seen by Dr. Hoffman, in Piedmont, W. Va., 20 miles distant, where he was chopping wood and apparently getting along with absolute comfort. It might be added that he was entirely bliud in the other eye.

The other case was also a very old colored man (88 years old). The operation was simple extraction, and atropine was instilled as usual at the operation. Before daybreak of the next day he was a raving maniac and had to be tied down to his bed. His bandage was torn off several times and he was incessantly tossing his head from side to side, until that too had to be secured so as to be as far as possible immovable. I did not dare look at the eye, as I supposed that it was lost. He did not recover his reason for a week, and all that was done was to apply hot moist compi-esses to the eye. When he became rational and I was enabled to get a satisfactory view of the eye I found a rather small pupil, a slight prolapse, but very little pericorneal congestion. On the tenth day he seemed to be completely himself again, and as the eye evidently needed a mydriatic, one drop of a solution of atropine (4 gr. — si) was instilled and the nurse was instructed to repeat the dose at bedtime. When I returned to the hospitiil the next day I found that during the night he had jumped out of the window — 20 feet from the ground — scaled a high iron-spiked fence and was making off when overtaken by an orderly. Notwithstanding all this exposure he obtained 4^ vision. Nothing was done for the prolapse, which flattened out entirely.

Another interesting case was where the auterior chamber


  • At the meeting of the Amer. Oph. Soc. only 147 cases were

reported in my second series. Since the meeting I have operated upon eleven cases.


October, 1897.J


JOHNS HOPKINS HOSPITAL BULLETIN.


201


remained open for seventeen days. I have seen explanations for tliis phenomenon, but none seem adequate. The opei'ation was the combined one, and the wound had united about half way ujj on one side and the rest of the incision remained open. More than once during these seventeen days a spatula was jmssed beneath, the corneal flap, and it was easily seen that no uuion had taken place. The operation so far as could be seen appealed to have been normal, that is to say there was not the slightest hitch in any of the steps. Atropine and compress bandage were employed, and two weeks after he left the hospital his vision was jW Eight months later he returned to the hospital with serious iritis, and since then vision has been lost, though he still has light perception.

Iridectomy was pei-formed in 102 cases and simple extraction in 42 cases. Soft cataract was operated upon by needling in three cases.

In thirty-one cases the vision was not tested. Three of these cases were in very young children and any subjective test would have been very unreliable. The remaining twenty-eight were ones which I had operated upon at a distance and most of whom I saw only once after the operation. A number of cataract glasses were sent to them from which to make a selection, and in this way I learned to what extent the operation had benefited the patient. It will be seen from the table that the operation and healing process were uncomplicated in all of these cases and all obtained useful vision.

Tlie failures were as follows: C«*e 54. The operation was smooth, and when the bandage was removed she could see large objects in the room. This was on the seventh day. Two days later iritis of a very sluggish character developed, and in spite of all treatment ended in closed pujjil and light perception. Dr. H. Harlan of this city operated on the other eye and obtained good vision, but he told me that the ojDeration was also followed by iritis.

Cage 72 had an exactly similar history. Case 95 was one which I had treated for several months for dacryocystitis. Her left eye had been operated upon by a New York oculist two years previously, and the cause of the failure in the case of that eye was no doubt the same as in the case of the eye upon which I operated, for both eyes were affected with dacryocystitis. When first seen she had a fistulous opening which had been discharging for several months. Before operation she was under treatment for at least five months, during which time the fistula had closed and the epiphora had almost disappeared. She understood the danger, but being totally blind in the other eye, wanted the operation performed. The cornea sloughed within a week after the operation.

Case 137 was that of a man 81 years old. On opening the eye on the third day there was a very offensive discharge on the bandage and between the lids, and beginning clouding at the edge of the corneal wound. Vigorous local and constitutional treatment, however, prevented the corneal trouble from extending and he was left with a clear cornea and closed pupil. I think that I could have converted this failure into a success (as in Case 190) by iridotomy, but a few days before the proposed operation he was attacked with pneumonia and died on the eighth day.


The last case was that of an old colored man (Case 128) and the history here was similar to Cases 54 and 72.

In one case (male, both eyes, 67 and 68), the patient had good light perception, but after the extraction of the cataracts it was observed that while he could move about somewhat better, his sight continued very poor, and this was explained by the existence of optic nerve atrophy in both eyes.

In Cases 53 and 307 a cataractous lens (congenital) had undergone calcification and presented a bright white mass in the pupil. The operation was simply for cosmetic purposes.

As to prolajjse of the iris. In the 42 cases of simple extraction there were five prolapses. In three of these cases nothing was done, though in Case 181 the prolapse looked as though it would extend throiigh the entire wound. Under a compress bandage, however, and atropine the hernia smoothed over and she has now vision f^. In Case 182 the prolapse got worse from day to day till it nearly filled the wound, and it continued bulging more and more. There was no hernia on the second day when the eye was inspected, but he bad a little gush of tears that night followed by pain, and a small hernia was visible the next day. On the eighth day, fearing that the eyeball would be permanently disfigured (to say nothing of loss of sight), the protruding iris was cut off. There is now not the slightest ectasia of the cornea so far as can be seen, and the patient has f^ vision.

In these last two cases lachrymation and photophobia were present to a marked extent and some little pain was felt at the time when the prolapse occurred, but after this pain was conspicuously absent. So far as could be seen there were no evidences of infection in any of the cases of prolapse. When I say evidences I mean cloudy media and exudates. I think that the absence of infection in these and similar cases is to be attributed to the fact that the wound is filled with the protruded iris and probably there is no way for the bacteria to make entrance into the anterior chamber. The profuse lachrymation which is usually present must be regarded as a more or less protection from a mechanical point of view, i. e. to some extent in washing away bacteria. And I think that an examination of the statistics of simple extraction will disclose the fact that the failures are as a rule not associated with prolapse.

In commenting upon the visual results it will probably strike many as singular that |J was obtained only four times, but this may be explained by the fact that discission was performed only ten times and that in quite a number of cases (31) I made no test of the vision.

In all of the operations the incision was made well within the liinbus of the cornea and still a little further in at the top of the incision. The latter includes usually something less than half the circumference of the cornea.

The instruments with the exception of the knife are boiled. The knife is allowed to remain in Squibb's absolute alcohol for 20 minutes. The eyebrows and that side of the face are covered with a cloth saturated with a solution of sublimate 1:1000. Both the cocaine and atropine solutions are boiled in test tubes and only used once. Small pledgets of cotton secured by sponge holders and boiled are used for removino- debris from the field of operation, such for instance as strings of mucus and small clots of blood. The uuoperated eye is closed till the second day and a small pad of sterilized absorbent cotton is placed over the operated eye and over this a four-tail bandage. The eye is inspected on the second day, and earlier if there be unusual pain. The room is darkened, but is not uncomfortably dark. The patient is allowed to get up on the second day, and the bandage is removed on the seventh day, though there was a time when I removed it earlier. The following is the arrangement of the visual results:

20 I 1

TS '^^

U 35


2 Qfi

717 ^°

20 Of?

20 R

2110 "

Vision not tested .31

Atrophy of the optic nerve 2

Cosmetic purposes 2

Failures 5

158

Successes in the first series 48

Failures iu the first series 2

Total number of cases operated upon 208


No.


Sex.


Age.


Health.


Cataract,


Operation.


Healii.g- process. Duration of treatment.


Primary Vision.


51


Male.


77.


Good.


Hard. R. E.


Iridectomy, smooth.


Uncomplicated.


2 weeks.


20/70


52


Male.


75.


Good.


" "


11 II


Mild iritis.


2 "


20/100


53


Male.


36.


Good.


Calcareous. R. E.


.1 11


Uncomplicated.


2 "


Light perception.


54


Female.


50.


Good.


Hard. L. E.


" "


Iritis.


6 "


" "


55


Male.


71.


Good.


" "


It 11


Uncomplicated.


2 "


20/.30


56


Female.


68.


Bad.


" "


Escape vitreous.


Iritis.


5 "


20/70


57


Female.


66.


Good.


" "


Iridectomy, smooth.


Uncomplicated.


2 "


Not tested.


58


Female.


72.


Good.


R. E.


11 II


"


2 "


20/26


59


Female.


65.


Bad.


L. E.


11 11


Iritis.


4 "


20/100


60


Male.


70.


Good.


R. E.


" "


Uncomplicated.


2 "


20/30


61


Male.


50.


Good.


" "


11 11


"


2 "


20/40


62


Male.


50.


Good.


L. E.


II II


"


2 "


20/40


63


Female.


55.


Good.


"i ^.•■■^■


11 11



2 "


211/100


64


Female.


60.


Bad.



11 11


"


2 "


24/40


65


Male.


55.


Good.


!! L.E.


11 11


Mild iritis.


5 "


20/70


66


Female.


62.


Good.



11 11


Uncomplicated.


2 "


Not tested.


67


Male.


75.


Bad.


" "


Simple Ext.


"


2 "


Atrophy.


68


Male.


75.


Bad.


R. E.


Iridectomy.


"


2 '•


0. Nerve.


69


Female.


60.


Good.


" "


"


"


2 "


20/40


70


Female.


60.


Good.


L. E.


"


"


2 "


20/70


71


Female.


66.


Good.


R. E.


"


Iritis.


3 "


20/100


72


Male.


80.


Good.


L. E.


"


Irido-cyclitis.


8 "


Light perception.


73


Male.


63.


Good.


" "


"


Uncomplicated.


2 "


20/30


74


Male.


66.


Good.


R. E.


"



2 "


20/20


75


Female.


71.


Good.


L. E.


"


"


2 "


20/70


76


Female.


50.


Good.


R, E.


"


"


2 "


Not tested.


77


Female.


61.


Good.


L. E.


"


Mild iritis.


3 "


20/40


78


Female.


66.


Good.


R. E.


"


Uncomplicated.


2 "


20/40


79


Female.


54.


Good.


L. E.


"


"


2 "


20/40


80


Male.


75.


Good.


R. E.


"


"


2 "


20/70


81


Male.


71.


Good.


" "


"


"


2 "


Not tested.


82


Female.


63.


Good.


',! L.^E.


•'


Vitreous lost. Iritis.


4 "


20/100


83


Female.


50.


Good.


(t


"


Uncomplicated.


2 "


20/70


84


Female.


51.


Good.


R. E.


"


"


2 **


20/40


85


Male.


80.


Bad.


" "


"


"


5 "


20/100


86


Male.


64.


Good.



"


"


2 "


20/70


87


Male.


54.


Good.


L. E.


"


"


2 "


20/40


88


Male.


66.


Good.


R. E.


"


"


2 "


Not tested.


89


Male.


60.


Good.


" L. E.


"


"


2 "


11 11


90


Male.


.57.


Good.


R. E.


"


1'


2 *'


20/40


91


Male.


51.


Good.


L. E.


"


"


2 "


20/100


92


Female.


47.


Good.


II .1


"


"


2 "


20/100


93


Male.


55.


Good.


R. E.


"


"


2 "


20/70


94


Male.


71,


Good.


" "


"


"


2 "


20/70


95


Female.


65.


Bad.


" "


Escape vitreous.


Irido-cyclitis,


2 "



96


Female.


52.


Good,


L. E.


Iridectomy.


Uncomplicated.


3 "


20/200


97


Female.


53.


Good.


R. E.


"


"


3 "


Not tested.


98


Female.


77.


Good.


L. E.


"


Iritis.


4 "


20/100


99


Male.


56.


Bad.


R. E,


■'


Uncomplicated.


2 "


20/30


100


Male.


58.


Good.


L. E.


"


"


2 "


Not tested.


101


Male.


54.


Good.


R. E.


"


"


2 "


20/40


102


Male.


46.


Good.


L. E.


"


••


2 "


20/70


103


Female.


76.


Bad.


R. E.


"


"


2 "


Not tested.


104


Female.


64.


Good.


11 11


1'


"


3 "


20/40


105


Male.


.50.


Good.


II 11


"


"


2 "


20/70


106


Male.


65.


Bad.


L. E.


"


"


2 *'


20/70


107


Female.


60.


Good.


" "


"


"


2 "


20/40


108


Male.


72.


Good.


R. E.


"


"


2 "


20/40


October, 1897.1


JOHNS HOPKINS HOSPITAL BULLETIN.


203


No.


Sex.


Age.


Health.


Cataract.


Operation.


Healing process. Duration of treatment.


Primary Vision.


109


Female.


61.


Good.


Hard. L. E.


Iridectomy.


Uncomplicated.


3 weeljs.


20/70


110


Male.


79.


Good.


" "




"


2 "


20/100


111


Male.


55.


Good.


R. E.




"


2 "


20/40


112


Male.


80.


Good.


L. E.




"


2 "


20/70


113


Female.


56.


Good.


" "




"


3 "


20/100


114


Female.


63.


Good.


" "




"


3 "


Not tested .


115


Male.


72.


Good.


" '•




"


2 "


20/100


116


Male.


81.'


Good.


" "




"


2 "


20/7(t


117


Female.


66.


Good.


R. E.




"


2 "


20/70


118


Female.


50.


Good.


" "




"


2 •'


20/40


119


Female.


49.


Good.


L. E.




"


2 "


20/100


120


Female.


48.


Good.


R. E.




"


3 "


20/70


121


Female.


53.


Good.


" "




"


2 "


20/30


122


Male.


68.


Good.


L. E.




"


2 "


20/40


123


Male.


64.


Good.


" "




"


2 "


Not tested.


124


Female.


62.


Good.


" "




"


2 "


II II


125


Male.


7.


Bad.


Soft. R E.


Needling.


"


2 operations.


" "


126


Male.


7


Bad.


L. E.


"


"



11 11


127


Male.


Si'.


Bad.


Hard. L. E.


Iridectomy.


"


3 weeks.


20/40


128


Male.


81.


Bad.


R. E.


"


Iridocyclitis.



Light perception.


129


Male.


22


Good.


Soft. R. E.


Simple.


Uncomplicated.


2 weeks.


Not tested.


130


Male.


30'.


Good.


" "


if


"


2 "


20/200


131


Male.


44.


Good.


Hard. L. E.


Iridectomy.


"


2 "


20/100


132


Male.


4.


Good.


Soft. L. E.


Needling.


"



Not tested.


133


Male.


77.


Good.


Hard. R. E.


Combined.


"


6 "


20/100


134


Male.


77.


Good.


L. E.




"


2 "


Not tested.


135


Female.


52.


Good.


R.E.




"


2 "


20/200


136


Male.


65.


Good.





"


2 "


20/70


137


Female.


57.


Good.


L. E.




"


2 "


20/40


138


Male.


69.


Good.






2 '■


20/40


139


Male.


82.


Bad.


(I (1


"


Escape vitreous.



No change but 3 weeks' vision. 20/70.


140


Male.


34.


Good.


Hard. R. E.


Simple Ext.


Uncomplicated.


2 weeks.


20/40


141


Female.


51.


Good.


" "




"


2 "


20/70


142


Female.


51.


Good.


L. E.




"


2 "


20/40


143


Female.


45.


Good.


R. E.




"


2 "


20/200


144


Male.


58.


Good.


II II




"


2 "


20/100


145


Male.


58.


Good.


L. E.




'<


2 "


20/70


146


Male.


61.


Good.


<i 11




Escape vitreous.


Iritis. 4 "


20/30,


147


Female.


47.


Good.


R. E.




Uncomplicated.


2 "


20/40


148


Female.


60.


Good.


II 1.




"


2 "


Not tested.


149


Female.


50.


Good.


w L.E.




"


2 "


11 11


150


Male.


60.


Good.





"


2 "


20/40


151


Male.


55.


Good.


II •!




"


2 "


20/70


152


Male.


44.


Good.


" "




"


2 "


20/70


153


Male.


48.


Good.


U II




"


2 "


20/40


154


Male.


51.


Good.


!'i ^;.^



"


2 "


20/70


1.55


Male.


62.


Good.





"


2 "


20/70


1.56


Female.


59.


Good.


II II




"


2 "


20/100


157


Female.


71.


Good.


L. E.




'•


2 "


20/70


1.58


Female.


73.


Good.


<" B;E.




"


2 "


20/40


159


Male.


47.


Good.





"


2 "


20/30


IGO


Female.


53.


Good.


11 11




"


2 "


Not tested.


161


Female.


62.


Good.


II <I




"


2 "


20/80


162


Female.


50.


Good.


II II




Iritis.


4 "


20/100


163


Female.


.58.


Good.


U tl




"


5 "


20/70


164


Female.


78.


Bad.


L. E.


Iridectomy.


"


7 "


Closed pupil.


165


Female.


66.


Good.


U II


"


Uncomplicated.


2 "


20/70


166


Female.


66.


Good.


R. E.


"


"


2 "


20/100


167


Male.


68.


Good.


11 <i


"


Ant. C, open


17 davs.


20/200


168


Male.


28.


Good.


Soft.


S. L. Extracture.


Uncomplicated.


10 "■


Not tested.


169


Female.


47.


Good.


Hard. L. E.


Simple Ext.


  • '


2 weeks.


20/10


170


Female.


80.


Bad.


R. E.


Iridectomy.


Iritis.


5 "


20/200


171


Female.


65.


Good.


II 11


"


Uncomplicated.


2 "


20/70


172


Male.


88.


Good.


L. E.


Simple Ext.


Prolapse iris.


3 "


20/100


173


Female.


70.


Bad.


R. E.


II II


Iritis.


4 "


20/70


174


Female.


70.


Bad.


L. E.


Iridectomy.


Uncomplicated.


2 "


20/70


175


Male.


44.


Good.


'<! ^;.^

Simple Ext.


"


3 "


20/40


176


Male.


48.


Good.



Prolapse.


5 "


20/30


177


Male.


71.


Good.


II 11


Iridectomy.


Uncomplicated.


2 "


Not tested.


178


Female.


70.


Good.


II II


"


"


2 "


20/100


179


Female.


61.


Good.


L. E.


"


"


2 "


20/40


180


Female.


67.


Good.


R. E.


"


Iritis.


4 "


20/40


181


Female.


66.


Good.


L. E.


Simple Ext.


Big prolapse.


5 "


20/40


182


Male.


47.


Good.


!' •^■i'^

"


II


4 "


20/30


183


Female.


58.


Good.



Iridectomy.


Uncomplicated.


2 "


20/40


184


Female.


70.


Good.


11 11


"


"


2 "


Not tested.


185


Female.


50.


Good.


11 11


Simple Ext.


"


2 "


20/100


186


Male.


67.


Good.


!'. ^u-^

Iridectomy.


"


2 "


20/20


187


Female.


77.


Bad.



Simple Ext.


"


2 "


20/100


188


Female.


77.


Bad.


R. E.


Irid


Bctomy.


Iritis.


4 "


20/100


204


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 79.


No.


Sex.


Age.


Health.


Cataract.


Operation.


Healing process. Duration of treatment.


Primary Vision.


189


Male.


83.


Good


Hard. L. E.


Simple Ext.


Uncomplicated.


2 "


Not tested.


190


Female.


80.


Good.


U It


Iridectomy.


Closed pupil, but


iridotomy pave.


20/2C0


191


Female.


70.


Good.


R. E.


"


Uncomplicated.


2 weeks.


20/30


192


Female.


62.


Good .


" "


"



2 "


20/70


193


Male.


50.


Good.


" "


Simple Ext.



2 "


20/70


194


Male.


55.


Good.


" "


" "


"


2 "


Not tested.


195


Male.


60.


Good.


" "


" "


"


2 "


20/100


196


Male.


72.


Good.


" "


" "


"


2 "


20/70


197


Male.


72.


Good.


L. E.


" "


"


2 "


20/70


198


Female.


70.


Good.


" "


Iridectomy.


"


2 "


2(1/20


199


Female.


70.


Good.


R. E.


"


Slight iritis.


3 "


2<i/100


200


Female.


68.


Good.


L. E.


Simple Ext.


Uncomplicated.


2 "


20/40


201


Female.


66.


Bad.


R. E.


" "


Iritis.


4 "


Not tested.


202


Female.


68.


Delicate.


" "


Iridectomy.


Uncomiilicated.


2 "


" "


203


Female.


65.


Good.


" "


"


"


2 "


20/40


204


Female.


66.


Good.


L. E.


"


"


2 "


Not te&ted.


2 '5


Female.


60.


Good.


R. E.


"


"


2 "



20(i


Male.


44.


Good.


L. E.


"


"


2 '■


" "


207


Male.


50.


Good .


R. E.


"


"



Cosmetic.


20S


Female.


55.


Good.


" "


"


"


2 "


Not tested.


PAROTITIS FOLLOWING VISCERAL INFLAMMATION.-A REPORT OF TWO CASES.


(Service of Dr. O.sler.) By a. Duval Atkinson, M. D.


It is well known that parotitis is a complication in pyaamia and many infections diseases. There seems also to be a relation between the parotid gland and the generative organs, and an apparent sympathy (as pointed out by Stephen Paget in 1886) between the parotid gland and the abdominal viscera. Cases illustrating it are, however, of sufficient rarity to warrant the rej)ort of the following histories.

Case J. Parotitis following a supposed gastric ulcer. — A female, aged 34, single, by occupation housemaid, was admitted December 16th, 1895, complaining of general weakness and vertigo. Her family history was good ; her mother died of "dropsy": there was no history of titberculosis. She had always enjoyed good health until one year ago. She had had none of the diseases of childhood. The catamenia began at fourteen and were always regular until a year ago. She had not menstruated for four months. She had been sick during the past year, but not confined to bed. At the beginning of the illness her chief complaint was of a continual dull pain in the epigastrium and "cramps" in the legs, a condition which lasted for about one month, when the pain left the abdomen, but not the extremities. In them it persisted with the utmost severity, being of a shooting, darting character, coming on often in paroxysms lasting several minutes. At the height of these pains a feeling of "pins and needles" would be felt in the hands and fingers. During the six months previous to her admission her arms and hands had been swollen to some extent, also her eyelids, the latter especially in the early morning ; her eyesight had been failing.

She took to bed December 9th, 1895 (eight days before entrance. Late in the afternoon of that day she began to feel weak and nervous, and had a gnawing sensation in the epigastric region. Nausea immediately followed, and she vomited a considerable ([uantity of bloody-looking material. Four hours later she again vomited a considerable quantity of material which the patient thought was pure blood. She remained in


bed on account of her extreme weakness until she came to the hospital.

Physical Examinatioii. Patient's skin and mucous membranes were j)ale ; sordes on lips ; tongue pale, moist, and somewhat cracked. Distinct pulsation in external jugulars; pulse 25 to the quarter, regular in force and rhythm, tension distinctly raised ; vessel wall a little thickened.

The thorax was long ; costal angle narrow ; expansion only fair, but apparently equal. Respiration over front of chest was negative; clear on percussion. Over the back the breath sounds were quite clear.

Heart. Point of maximum cardiac iinpulse diffuse over fifth and sixth spaces, in and a little outside the nipple line; relative dullness was at the upper border of the third rib, extending to the nipple line and a little beyond the left sternal margin. At the point of maximum cardiac impulse the first sound was loud and booming, accompanied by a blowing systolic murmur which was heard as far out as the anterior axillary line. The second sound was accentuated. A systolic murmur was also heard in the aortic region, where the second sound was sharp and loud. Over the sternum the murmur was increased and the second sound was more booming. At the costal angle the murmur was very distinct and the second sound was greatly increased in intensity.

Hepatic flatness began at the sixth intercostal space and extended to the costal margin in the mammillary line; the border was indistinctly felt. Spleen not palpable. No cedema. Eefiexes normal. Blood count showed 2,314,000 red corpuscles to the cubic millimetre; white corpuscles, 8000; hajnioglobin 30 per cent. The urine was pale yellow in color ; specific gravity varied from 1010 to 1006; there was a decided trace of albumen. Microscopically granular casts were seen. There were no rigors.

During the night of Dec. 16th, 1895, the patient began to complain of pain, and tliero was some swelling in the region


OCTOBEll, 1897.]


JOHNS HOPKINS HOSPITAL BULLETIN.


205


of the left parotid gland. The next morning (two days after entrance) the following condition was noted. The patient presents great swelling of the left parotid gland. The swelling extends nji above the zygoma, and behind far over the mastoid. Below there is a marked amount of infiltration in side of neck, extending to the angle of the mouth. The swelling lifts the lobe of the ear. It is rounded, tense, hot, and very painful. The tongue is a little swollen. Nothing exudes from Steno's duct when external pressure is made over the gland. The abdomen is negative. There is no general enlargement of the superficial glands of the body.

At 13 noon, although no fluctuation was obtained, the gland was incised. Numerous small foci of inflammation were discovered, from which exuded a little creamy pus. Cover-s]ij)s from these areas showed streptococci and a large bacillus ; the latter was supposed to have come from the mouth. Cultures showed a pure growth of streptococcus, the bacillus not growing.

The following day, December 20th, the pain in the region of the neck had in a measure subsided; the swelling, however, remained about the same ; there was marked oedema of left eyelid.

The patient did fairly well until the 34th, the swelling and tedema of eyelids remaining about the same. On that day she was extremely pale, pulse 100, dropping a beat occasionally. The swelling of the cheek was perhaps a trifle less; she breathed noisily ; no infiltration in the lower neck. The patient sank rapidly and died. Unfortunately no autopsy was allowed. The diagnosis of parotitis, gastric ulcer, and chronic interstitial nephritis was made.

Case II. Cholecystitis (post typhoidal) complicated by double parotitis. — J. L., single, age 34, German, butcher by occupation, was admitted to Ward F, November 25, 1895, complaining of continual headache, pains in his muscles and joints. His family history was good ; there was no history of tuberculosis. His only disease during childhood was scarlet fever, from which he made a complete recovery, with no sequelae, and excepting an attack of rheumatism, which confined him to bed nine months in 1893, had always been a strong, able-bodied man. He gave no history of syphilis or gouorrhoeal infection. Had been a moderate drinker. The history of his present illness was that about one week before his admission he began to have headache, chills and nausea, accompanied by vomiting. The diagnosis of typhoid fever was made, and the patient had a typically mild course of fever, which was treated by means of the ice-baths. His temperature reached normal on December 5th, ten days after entrance. The urine showed a distinct diazo reaction, and there was a trace of albumen. The spleen was easily palpable, and there were a few typical rose spots. The liver was never palpable. Blood negative for malarial organisms. No leucocytosis. His convalescence was uninterrupted, and he was discharged well, January 1, 1896.

The patient was readmitted November 30, 1896, eleven months afterwards, complaining of headache and general weakness, stating that he had been feeling badly for ten days. The chief symptoms seemed to have been headache, muscular and slight abdominal pain. Two days before


entrance he had had a slight chill followed by fever and sweating. On entrance his temperature registered 103.4°, pulse 27 to the quarter minute, full and strong. The physical examination was negative save for a slight enlargement of the spleen and some rigidity of the right rectus muscle. The liver was not palpable and the hepatic flatness was not increased. The blood was entirely negative for malarial organisms, and there was no leucocytosis. The conjuuctivEe were injected, but there was no jaundice. No bile was found in the urine. His temperature, which reached 103° on the evening of his entrance, quickly dropped to normal, and the man was discharged December 15th, quite well, with no definite conclusions being reached concerning the nature of his trouble.

He again applied for admission March 5, 1897, stating that for three days he had had chills, accompanied, he thought, by fever, headache and pains in his back and limbs. His bowels had been very costive for some time.

The physical examination was as follows : Well nourished, strong-looking man ; face flushed; eyes bloodshot ; lips a trifle cedematous ; tongue had a slight brown coat. Pulse, 33 to the quarter minute, dicrotic ; capillavy circulation rather sluggish. Thorax symmetrical, expansion equal; an occasional sonorous rale was to be heard over chest and axillae. Heart sounds clear. Spleen just palpable on deep inspiration. Hepatic flatness began at the sixth rib, extending one finger's breadth below the costal margin. The muscular resistance of the abdominal wall was such that it was utterly impossible to palpate it. In the mammillary line there were 13 cm. of hepatic flatness. (Pain was complained of whenever deep palpation was attempted in the hypocondriac region.) On the following day, March 6th, there was no essential change in his condition. The morning temperature registered 104.3°, and that of evening 103°. There was well-marked tenderness on pressure in the hypocondriac region, and pressure between the crest of the ilium and ribs on the right side caused pain. The most tender part appeared to be just at the region of the gall-bladder. The conjunctivae were a little muddy, but not distinctly jaundiced. There was- a leucocytosis amounting to 11.300 to the cubic mm. The urine was negative, but no test for bile was made. On March 9th the conjunctivae were slightly yellow, and the urine reacted for bile. There was still great tenderness in the region of the gall-bladder. His temperature, which had been gradually falling, reached normal at 2 a. ni., where it remained until the 12th, when it was again elevated. On that day both parotid glands were swollen, the right more than the left. They were hot and very tender to pressure. No fluctuation was obtained. On the loth both glands were greatly swollen, the tissue of the face and neck was infiltrated, and eyelids (Edematous. The skin over the parotid glands was red, the gland itself imparting a hard infiltrated sensation to the examining hand. Both papillae at orifice of duct were swollen, and pus could be forced out. Although the patient was in poor condition, his temperature registering 102.8°, he insisted upon leaving the hospital, and was therefore discharged.

Cultures from the Ijlood on agar-agar and bouillon proved neo-ative. Diagnosis: Cholecystitis (post-typhoidal), com


206


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 79.


plicated by double parotitis. Later both parotids were incised, the bacteriological esamiuation showing a pure growth of staphylococcus aureus. The patient is now quite well.

The cases in many ways correspond to some of those referred to by Stephen Paget in the London Lancet for 1886, and spoken of in more detail in the British Medical Journal in 1887. In his series parotitis followed injury and diseases of the peritoneum, generative organs, and abdominal viscera. Two followed a supposed gastric ulcer. Of the 101 cases cited, 10 were due to injury of the urinary tract; 18 to diseases of the alimentary tract; 33 to injury or disease of the abdominal wall and peritoneum, or to the pelvic cellular tissues, and 50 to temporary derangement of the generative tract. He states that parotitis after abdominal or pelvic injury or disease is not as a rule accompanied by signs of septiegemia or pya3mia. Of his 101 cases mention is only made in 15 of septic symptoms. 37 died; of these 3 were over eighty years of age ; 3 had internal cancer ; 3 had perforation of the bowel ; and 3 had strangulated hernia; 7 had undergone severe surgical operation involving abdominal section ; 13 had septicEemia or pyfemia; 1 had infantile syphilis ; 1 had marasmus; and 1 had heart trouble. He adds that death was not due to parotitis joer se, but to a primary lesion, and he is ujiable to state to what extent parotitis is a dangerous complication. Its period of incubation is unknown, but in his opinion it is from one to thirteen days. There is as a rule no marked disturbance to general health, no rigors, and no high fever. On the other hand symptoms may be more severe from the onset, and great disturbance in general health may be noted. Eigors were noted in only 4 cases. In regard to the termination of the parotitis, whether by resolution or by suppuration, the figures show that out of 73 cases which give information on the point, 45 suppurated and 33 were resolved, and out of 45 that suppurated 34 died; but out of the 33 that resolved without suppuration only one died (in all probability from cancer). In other words, he thinks that they did not die because the parotids went on to suppuration, but that the parotids suppurated because they were going to die. In cases of undoubted septicasmia or pyemia the parotids always went on to sujipuration.

'I'he only autopsy reported by Paget is that of a woman dying from the effects of the removal of a sarcomatous growth of the mesentery, having parotitis as a complication. On section the parotid was found to be evenly and in every part infiltrated, not with pus, but with a reddish, slightly turbid fluid, causing it to look like a section of the spleen. There were no abscesses anywhere. Just in the proximal end of the duct where it left the gland lay two or three drops of healthy pus and a tiny calculus. The acini were separated, compressed, and breaking up, and here and there were seen ducts filled with the same small round cells as were infiltrated among the acini. No bacteriological examination was made. Mr. Paget cites a case reported by Rosenbach of parotitis following operation for strangulated hernia, in which staphylococcus aureus was obtained. He further states that this form of parotitis is in many ways a peculiar lesion, so far as l)eingdue


to septicemia. It was in 93 cases an isolated lesion, unaccompanied by any other lesion like itself, having no fixed period of incubation, and running no common course. Its invasion is not as a rule marked by rigors or great rise of temperature. It may subside and swell up and subside again. These facts make it impossible to say that this form of parotitis is due to any ordinary form of septicaemia. It is not, he thinks, due to inflammation following a parched and sore mouth, as the mouths of pyaBmic or septicaemic patients are not, as a rule, more parched than those of other patients. Also, he does not think that it is merely due to inflammation of the lymphatic tissue which is in the gland substance. " Admitting that the general condition of the patient, especially in cases of septicemia and pyaemia, is considered in the production of this form of parotitis, must we not take into consideration the reflex action of the nervous system, as the influence, direct and reflex, of the nervous system upon the salivary glands is shown in countless ways; viz. gastritis may be followed by salivation or arrest of salivary secretion. Parotitis may follow gastric ulcer, gastrotomy, etc. Even operations on the rectum and again diseases of the thoracic viscera cause inequality of the pupils, differing not only in size, but in their susceptibility to light. Thus, with regard to pyjemia after abdominal or pelvic lesions, we may admit that the general condition of the patient may help to cause it, without denying the local influence of the nervous system."

A. J. Oribb (Lancet, 1886) reports two cases ; in one jiarotitis followed irritation of the genito-urinary tract, and in the other ovaritis occurred in connection with parotitis. And again, Harkin (Lancet, 1886) reports parotitis in a woman aged 43 as one of the first symptoms of three successive pregnancies, no suppuration being present. These cases seem to point undoubtedly to some latent sympathy between the parotid glands and the organs either covered by or closely adjacent to the peritoneum. It is, however, difficult for us, with our present bacteriological knowledge, to conceive of inflammation being established in organs far remote from the seat of irritation by reflex causes alone, without the presence of micro-organisms. An interesting case, and one bearing a close resemblance in some respects to those cited, is one reported by W. Legg in the Pathological Society Reports for 1869, in which parotitis was a complication in contracted kidney and atheroma in a lad aged 16, who was admitted to the University College Hosjiital for albuminuria. Nine days after admission he complained of pain on right side of face. The day after well-marked right parotitis was noted. The swelling continued for eight days, when the patient died suddenly. There was found to be no obstruction to Steno's duct; the gland tissue was pale grey in color, not at all reddened, rather harder than natural, and on section there flowed from the cut surface a large quantity of pale greyish white fluid, somewhat thin, showing under the microscope a large number of rounded cells, larger on the average than pus corpuscles, having rather granular contents, and single small bright nuclei. The gland was the seat of small abscesses varying in size from a pin head to a barley corn. Microscopically was seen a great increase in epitiielial elements, the acini being iilled with them. The arteries wore atheromatous


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and the kidneys contracted. No mention is made of lesions in other organs.

W. B. Morrow, in the Montreal Medical Journal of March, '96, has related the histories of three cases of parotitis fol]pwing pelvic disease. And Herbert and Hawkins, in the British


Medical Journal of April 10, 1897, report two cases of operation for jjerforation of gastric ulcer, in one of which there was a double parotitis three days after operation, the patient eventually making a complete recovery, the glands subsiding without incision being necessary.


PALPATION OF THE FCETAL HEART IMPULSE IN PREGNANCY.

By Douglas F. Duval, M. D., Assistant Resident Ognecologist.


It is not generally known that the impulse of the fcetal heart may under certain conditions be actually felt beating through the abdominal walls of the pregnant woman.

In this country but two cases have been observed, those of Dr. Kelly, which I now report. The first was in 1884 and the second in 1895. They represented the right bregmatic-iliacanterior and left occipito-iliac-posterior presentations, the latter being observed in the eighth month of pregnancy, all previous cases having been during labor.

Of the other observers, Fischel, in 1881, was the first to publish a definite account describing accurately three cases in which this phenomenon occurred. These cases represented the left bregmatic-iliac-anterior, the right occipito-iliac-posterior and the left mento-iliac-auterior presentations. Valenta, however, in 1885, claimed priority of observation, stating that he had noted it in 1860 in a first face presentation, and had recorded it in his "Text-Book on Midwifery," and that since then he had repeatedly spoken of its importance as a diagnostic sign in anterior face presentations. Fleischman in 1885, stimulated by Fischel's communications, published an interesting case in which this phenomenon was observed in a right men to-iliac-anterior presentation.

The following is a brief account of the various cases :

Case I. Observed by Dr. Kelly, in Kensington, Philadelphia, in 1884. Multipara, of medium build, mother of four or five children, abdominal walls moderately thin. A right bregmatic-iliac-anterior presentation. Membranes ruptured, OS half dilated, brow just engaging. The impulse of the foetal heart was forcible and distinctly palpated over an area about 3 cm in diameter ; to the right and about half way between the umbilicus and Poupart's ligament, separate beats were easily counted, 130. The child was born living after a protracted labor and manual rectification of position.

Case II. Observed by Dr. Kelly. Patient short brunette, well nourished, abdominal walls not thin, eighth month of her first pregnancy. A left occipito-iliac-posterior presentation. Heart sounds heard loud over an area 10x10 cm., and easily counted 140. On moderate pressure a rapid fluttering sensation was clearly distinguished over an area about 2.5 cm. in diameter. The separate beats could not be distinguished; a few days later, on examination, the heart impulse could not be felt. The patient has since passed through a normal confinement.

Fischel's Cases.

Case I. Mi. 36, 1 para, well nourished, strong. Pains began on 30th at 1) p. m. Li(juor auinii discharged on 31st at


13.15 a. m. At 7.45 a. m. os 6 cm. in diameter. Foetus in left bregmatic-iliac-anterior presentation. Heart sounds to the left and below umbilicus. At 13.15 fcetal heart impulse palpated to left and beside umbilicus, synchronous with foetal heart sounds, frequency 156-160. This phenomenon was observed for several hours. Change of presentation being impossible, craniotomy was performed.

Case II. Mt. 31. Well built, large, strong. Pains began at midnight. At 3 a. m. liquor amnii discharged. Entered hospital at 4 a. m. Cervix obliterated, back to the right, feet to the left above the umbilicus, chin 8 cm. above left os pubis, heart sounds above the symphysis. From this description very probably a right occipito-iliac-posterior presentation. The fcetal heart impulse was palpated just above the chin, easily demonstrable, frequency 156, maternal pulse 113. In the further course of labor, which was rapid and favorable, the impulse was palpated in the pauses between the pains, descending toward the symphysis and finally disappearing entirely, though the sounds continued to be heard. Examination of the child's heart after labor showed clearly that the sounds were of normal strength and clearness.

Case III. Mi. 30. 1 para, small, strongly built, moderately fat, abdominal walls thin. Pains began at 10 a. m. Entered hospital in the afternoon. External examination : Occiput above right os pubis, extremities to the left, heart sounds to the left of the umbilicus, loud and slow.' The presentation in this case was then a left meuto-iliac anterior. At 6.30 p. m. the heart impulse was clearly palpated 5 cm. to left of umbilicus. At 7.30 p. m. was 5 cm. to left of umbilicus, but lower. At 8 p. m. frequency ranged between 80 and 150 ; maternal pulse 66-73. At 11.30 p. m. heart impulse to left of umbilicus, but lower. Labor terminated at 13 m., fcetal heart sounds ceased two minutes before delivery, child stillborn.

Fleischman's Case.

Case I. Mt. 35. Abdominal walls thin and flabby. Entered hospital at 11 p. m., three hours after discharge of liquor amnii. Occiput over left os pubis, back to the left, heart sounds clearest four fingers' breadth to right of midline, chin to right and forward, forehead to left and backward. Evidently a right mento-iliac-anterior presentation. On the following morning the foetal heart impulse was palpated in the right hypogastrium, at the junction of the middle and lower thirds of a line drawn between the umbilicus and middle of Poupart's liganit'nt. In frequency doubled that of the maternal. 'J"he sounds were loud and clear.


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Fleischmau says: "The conditious iu this case for the observation of the pheuomenon were most favorable, the abdominal walls were thin and flabby and the liquor amnii had previously discharged, thus permitting the uterine walls to clasp firmly the foetal thorax."

The following is a summary of all the cases :

Fischel, 1881, three cases: Left bregmatic-iliac-auterior, right occipito-iliac-posterior, left meuto-iliac-anterior.

Valenta, 1885, one case: First face presentation (K. m. i. ant.)

Fleischman, 1885, one case: Right meuto-iliac-anterior.

Kelly, two cases : First iu 1884, a right bregmatic iliacanterior presentation; second iu 1895, left occipito-iliac-posterior presentation.

From the above it will be seen that the observation has been made in face, brow and occipito-posterior presentations — two of each. One may therefore infer that these are the most favorable presentations for the observation of this phenome


non ; especially is this the case in face and brow presentations, the fcetal thorax being arched forward and therefore in closer proximity to the maternal abdominal walls. In occipito-posterior jjresentations the festal curve is directed backward and consequently less favorable.

The liquor amnii also plays an important part, as shown by the fact that in all cases, with the exception of the second case of Dr. Kelly, the observation was made during labor. In this case one must naturally suppose that a small amount of liquor amuii was present. As for the maternal abdominal walls, they should be thin and flabby in order that there may be little hindrance to the transmission of the im^iulse of the foetal heart.

References.

American Text-Book of Obstetrics, Hirst, 1888. Fischel, Prager medicinische Wochenschrift, Nos. 13, 13, 39, 30, 1881.

Fleischman, ibid.. No. 35, 1885. Valenta, ibid., No. 45, 1885.


SQUAMOUS EPITHELIOMA IN A DERMOID OF THE JAW.

By S. M. Cone, M. D., Assistant in Surgical Pathology, Tlie Johns Hopkins University.


Few cases of epithelioma arising in dermoid cysts have been described. Taufier, whose article on carcinoma arising in dermoids of the ovary is very complete, knows of none originating in dermoids elsewhere. In none of the dissertations on dermoids of the ovary with carcinoma in their walls do we find reference to like tumors in other regions of the body. I can find but three cases and they are not very fully described. That of Franke, on an epidermoid of the ball of the thumb with carcinoma originating in it, is most complete. Czerny in 1869 reported a case in the coccygeal region, the first to be noted anywhere, which is interesting moreover because of the expression of the opinion that the squamous epithelium developed from cylindrical epithelium snch as is found in the intestinal tract, and the idea is expressed of the possibility of epithelium arising from connective tissue and lymph cells. Briddon reported a case before the New York Surgical Society and Dr. Thacher made the pathological report. This tumor was also from the coccygeal region. The sections which were kindly given me have some resemblance to the one I shall describe. The descriptions of those found in the ovaries are so much better described that it is best to reach our conclusions regarding origin and development through the gynecological literature.

Yamagiwa and Thumim have both reported cases this year. Thumim gives the literature on the subject up to date. Yamagiwa reports two cases, one of which he puts down as a glandular carcinoma developing from remains of a mammary gland in the dermoid. Thumim objects to including this among the dermoids with "carcinomatous degeneration" and rather thinks it to be part of a misplaced mammary gland forming a part of a teratoma of the ovary. ' If it is a true carcinoma it is the only one of its kind described ; the remain


ing eight cases arising in the ovary ;ind three elsewhere are all of the squamous cell variety.

All authors are careful to exclude the possibility of the growth of the epithelioma "per contiguitatem," both Tauffer and Thumim giving a list of doubtful cases. The analogous origin of carcinoma iu atheromas and other cysts lined by epithelium is mentioned by Lubarsch in his review of the subject, and many others refer to the subject as something not long discovered. A very interesting point is alluded to by Yamagiwa when in writing of his first case he refers to its resemblance to alveolar sarcoma or endothelioma. Such cases have been reported, but are rare.

The case to be reported is that of Patrick D., age i'i, blacksmith, who entered the surgical ward of the Johns Hopkins Hospital, June 30, 1894, with a tumor of the left lower jaw. Family history good ; past history good.

Present Illness. — In September, 1893, the patient noticed a pea-sized growth under the horizontal ramus of his left lower jaw. It began to pain him in November and grew rapidly with incessant pain. He refers its quickened growth to a fall when he injured the jaw.

Physical Examination. — The tumor extends from 1 cm. in front of the angle to the junction of the middle and outer third of the horizontal ramus of the lower jaw. It extends to the hyoid bone and appears to be the size of a small orange. It is fixed firmly, is sharply circumscribed and has smooth, rounded borders. It is firm in consistency except at the most prominent portion, where slight fluctuation can be felt. The skin is cedematous and red. At one point there is a small opening from which serum exudes on pressure. Teeth are normal. Alveolar process is not involved.

On June 35th the patient was operated on by Dr. Halsted.


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Tracheotomy was first performed, aud the pharynx being tamponed the tumor and left lower jaw were excised. The patient's recovery from the operation was uuinterrnptedly good. He was discharged on July 13th. He returned September 6, 1894, aud was treated for phthisis pulmonalis — tubercle bacilli beiug found in his sputum. He was discharged on September 14th unimproved and died at home of phthisis pulmoualis. No autopsy was performed.

Descrip/ioH of the tumor by Dr. Bloodf/ood. — The tumor is removed with an area of skin 8x6 cm. and a piece of the lower jaw