Difference between revisions of "The Johns Hopkins Medical Journal 12 (1901)"

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* Remarkable Cases of Hereditary Anchyloses, or Absence of Various Phalangeal Joints with Defects of the Little and Ring Fingers. By George Walker, M. D.,
 
* Remarkable Cases of Hereditary Anchyloses, or Absence of Various Phalangeal Joints with Defects of the Little and Ring Fingers. By George Walker, M. D.,
 
* Note on the Basement Membranes of the Tubules of the Kidney. By Franklin P. Mall,
 
* Note on the Basement Membranes of the Tubules of the Kidney. By Franklin P. Mall,
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* A Comparative Study of the Development of the Generative Tract in Termites. By H. McE. Knoweh, Ph.D
 
* A Comparative Study of the Development of the Generative Tract in Termites. By H. McE. Knoweh, Ph.D
 
* A Composite Study of the Axillary Artery in Man. By J. M. IIitzuot,
 
* A Composite Study of the Axillary Artery in Man. By J. M. IIitzuot,

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The Johns Hopkins Medical Journal - 12 (1901)

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The Johns Hopkins Medical Journal 12 (1901)

The Johns Hopkins Hospital Bulletin


BULLETIN OF THE JOHNS HOPKINS HOSPITAL.

Vol. Xll. - No. 118.

BALTIMORE. JANUARY. 1901.


Contents - January

  • The Removal of Pelvic Inflammatory Masses by the Abdomen after Bisection of the Uterus. By Howard A. Kelly, M. D., . . 1
  • Abstract. The Bacteriology of Cystitis, Pyelitis and Pyelonephritis in Women. By Thomas R. Buown, M. D., 4
  • The Intrinsic Blood- Vessels of the Kidney and their Signirtcauce in Nephrotomy. By Max Brodel, 10
  • Notes on jiC.obic Spore-Bearing Bacilli. By \V. W. Foud, M. D., r^.t.R., 13
  • Summaries or Titles of Papers by Members of the Hospital and Medical School Staff Appearing Elsewhere than in the Bulletin, 16
  • Proceedings of Societies:

The Johns Hopkins Hospital Medical Society, 17

Case 5of Asthma with Cyanosis, Extensive Purpura, Painful Muscles, and Eosinophilia [Dr. Osler] ; — Bisection of the Uterus in Hysterectomy [Dr. Kelly] ;— Exhibition of Surgical Cases

[Dr. Mitchell]; — Report of Cases from the Garrett Hospital for Children [Dr. Platt] ; — The Relation of Cholelithiasis to Disease of the Pancreas and to Fat-Necrosis [Dr. Opie]; — Secondary Syphilitic Eruption [Dr. Futcher] ; — Observations on Blood in Typhoid Fever [Dr. Thayer]; — Albumosuria [Dr. HAMBnRGEK]; — Exhibition of Pathological Specimens: Vegetative Endocarditis, Cystic Kidney, Carcinoma of GallBladder [Dr. Marshall]; — Congenital Absence of Pectoralis Major and Minor [Dr. Rosk] ; — Report of Gynsecological Cases [Dr. Miller] ; — Demonstration of a New Hemoglobinometer [Dr. Dare]; — Cirrhosis of the Stomach [Dr. McCrae]; — Abdominal Tumor containing a Dermoid Cyst [Dr. Mitchell] ; — Two Cases of Acute Pancreatitis [Dr. Bloodgood] ; — Tuberculosis of the Aorta [Mr. Longcope].

Notes and News, 38

Notes on New Books, 29

Books Received, 30


THE REMOVAL OF PELVIC INFLAMMATORY MASSES BY THE ABDOMEN AFTER

BISECTION OF THE UTERUS.^


By Howard A. Kelly, M. D.


I pointed out but recently (Johns Hopkins Hospital Bulletin, 1900, XI, p. 56, and Amer. Jour. Ohst., 1900; XLII, August) the great advantages which accrue from the bisection of the myomatous uterus in an abdominal enucleation in certain complicated cases. I now desire to call your attention to the great value of a somewhat similar procedure in certain cases of pelvic inflammatory diseases.

In most instances of pelvic infections, the ovaries are innocently, only accidently, involved in the inflammatory process, and as a rule one or both of them can be saved even though it is found necessary to sacrifice both uterine tubes. If one ovary is saved, the uterus must also be saved if pos


■ An address delivered before The Southern Surg. & Gyn. Assoc, Atlanta, Ga., November 13, 1900.


sible, as by doing this we conserve the function of menstruation as well as that of internal secretion of the ovary.

Where the ovaries are seriously involved in the disease, where they are converted into abscess sacs or into large hematomata, or where they are so densely and intimately matted in with the inflamed tubes that it is useless to attempt to save them, the removal of all the diseased organs together with the uterus is demanded wheneve - it is possible in this way: by freeing the tube and the ovary on the least adherent side first, and then after tying off the broad ligament and pushing down the bladder, and securing the uterine artery, the most difficult side is easily reached and enucleated, by cutting across the cervix and exposing the opposite uterine vessels and ligating them. The uterus is -then pulled up until the round ligament is caught and divided.


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 118.


At this point the operation may follow one of two courses according to the difRciilties encountered: in the iii-st place, if, after dividing the uterus and pulling it up, the remaining tube and ovary can be readily enucleated by peeling them out from below upwards by working with the fingers in the lower and anterior part of the pelvis, then the enucleation may be concluded by removing all the structures in one mass. In the second place, if the tube and ovary on the far side are densely adherent and offer any serious difficulties in the enucleation, then I would clamp off the uterus at its cornu and remove it with one tube and ovary, and so leave the more difficult side to be dissected out after emptying the pelvis, securing all the advantages of increased space and light (v. Figs. 1 and 2). I have previously described this method as that of enucleation by a continuous transverse incision from left to right or from right to left.



Fig. 1 shows the method of removing the uterus, in a case of pelvic inflammatory disease, by a continuous transverse incision beginning on the left side.

1 controls the left ovarian vessels.

2 controls the left round ligament; the next step Is to free the vesical peritoneum from the uterus and to push the bladder down ; this exposes the left uterine vessels which are now controlled by o.

4 represents the division of the cervix exposing the right uterine vessels controlled by n.

The division of the cervix is not directly across, a sliver or a snipe (4 to 6), is left in order to clamp the uterine vessels at a higher point.

6 is the ligature on the right round ligament and 7 that on the right ovarian vessels.

It is now my desire to describe a method of enucleation through an abdominal incision which is applicable to a class of cases still more difficult than those just referred to. I^et us suppose, for example, a case in which there are pelvic abscesses on both sides densely adherent to all the surrounding structures, including the uterus; we will also suppose that the uterus itself is almost or quite buried in a mass of adhesions. In such a case the plan I have just described is scarcely applicable, inasmuch as there is no easier side on which to begin to start the enucleation, for both sides present extreme difficulties.


The method of a continuous transverse incision does actually give us, it is true, a great advantage over the older method of tying down on both sides, for the simple reason that the enucleation of the farther side, wherever we begin, is always easier, even though the difficulties of the first side are just the same by either method.

If, now, I could devise any method by which the enucleation of both tubes and ovaries in such a case could be effected in a direction from below upwards, it is manifest that a great advantage would be gained.

The vaginal hysterectomists have thus far had a decided advantage over those of us who prefer to operate above the symphysis, in the greater facility with which the adherent structures can be detached when they are attacked in the direction from the pelvic floor upwards. In the method I am now about to describe, this decided advantage is secured



Fig. 3 shows an important modification of the method of enucleation described and shown in Fig. 1. When one side is densely adherent, it is best then to begin the enucleation with the opposite side in the order already described, and then after tying the round ligament at 0.

The next step then is to clamp the cornu uteri and remove the uterus with the tube and ovary of the side on which the enucleation was started.

The final step in the enucleation now is to remove the densely adherent side with forceps and scissors with all the advantages of abundant room and light afforded by the removal of the uterus.

for, and combined with the other great advantages of the abdominal route, that of increased room, and increased facilities of handling, abundant illumination, as well as the detection of various complicating conditions.

The steps are these: If the uterus is buried out of view, the bladder is first separated from the rectum and the fundus uteri found; then, if there are any large abscesses, adherent cysts, or hematomata, they are evacuated by aspiration or by puncture; the rest of the abdominal cavity is then well packed off from the pelvis.

The right and left cornua uteri are each seized by a pair of stout museau forceps and lifted up, the uterus is now incised in the median line in an antero-posterior direction,


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE I.



Fir., a shows the advaiitasics of :i bisection of the uterus euabling the surs:eon to remove the uterus before removing either tube and ovary, thus atl'ording all the conveniences of more room, abundant illumination and new avenues of approach indicated by the arrows.

Ligatures may be placed on tlie ovarian vessels as shown before cuucleatinir the uterine tubes .and the ovaries, when the vessels are accessible.



'ecMi^'r/ce


Fig. 4 shows the first step in the bisection of an adherent n^trotlexed uterus. The forceps catch the anterior face which is opened, then the bladder is |pushed down and the cervix divided Injin side to side as indicated by the arrows.


rfi


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE II.



Fig. .5. — After freeiuy; the cer\ix directiou from below up.


from its vaglniil end it is held up and the bisettiun cuuiijlrtnl as shown here, iu a



Fig. shows the bisection conipU'ted. Eaeh half of the uterus is now removed b.v uiiiilyin;;: ligatures as indieated by tin' arrows on tlie round liganieuts and the uterine cornua. The lateral iutlauiniatory masses are remo^'ed last of all.


January, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


and as the uterus is bisected, its eornua are pulled up and drawn apart. With a third pair of forceps the uterus f= grasped on one side on its cut surface, as far down in the angle as possible, includiiTg both anterior and posterior walls. The museau forceps of the same side is then released and used for grasping the corresponding point on the opposite cut surface, when the remaining inuseau forceps is removed. In this way two forceps are in constant use at the lowest point. I commonly apply them three or four times in all As the uterus ig pulled up the halves become everted and it is bisected further down into the cervix; if the operator prefers to do a pan-hysterectomy, the bisection is carried all the way down into the vagina. The uterine canal must be followed in the bisection, if necessary using a grooved director to keep it in view. The museau forceps are now made to grasp the uterus well down in the cervical portion, if it is to be a suprn-vaginal amputation, and the cervi.^ is divided on one side. As soon as it is severed and the uterine and vaginal ends begin to pull apart, the under surface of the uterine end is caUght with a pair of forceps and pulled up and the uterine vessels, which can now be plainly seen, are clamped or tied. As the uterus is pulled still further up, the round ligament is exposed and clamped, then finally a clamp is applied between the cornu of the bisected uterus and the tubo-ovarian mass, and one-half of the uterus is removed. The opposite half of the uterus is also taken away in the same manner.

The pelvis now contains nothing but rectum and bladder, with right and left tubo-ovarian masses plastered to the sides of the pelvis and the broad ligaments, affording abundant room for investigation of their attachments, as well as for deliberate and skillful dissection; the wide exposure of the cellular area over the inferior median and anterior surfaces of the masses, offers the best possible avenue for beginning their detachment and enucleation.

The operator will sometimes find on completing the bisection of the uterus that he can just as well take out each tube and ovary together with its corresponding half of the uterus, reserving for the still more difficult cases, or for a most difficult side, the separate enucleation of the tube and ovary after removal of the uterus.

The operation which I have just described is not recommended to a beginner in surgery; the surgeon who undertakes it must be calm and deliberate, and must bear in mind at each step the anatomical relations of the structures.

The most critical point is the bisection of the cervix and controlling the uterine vessels; if the cervix is slowly and ■cautiously severed with a steady traction on the uterus under perfect control, there is no danger of seeing the organ suddenly tearing out with rupture of the uterine vessels and frightful hemorrhage. As the divided cervix is pulled apart, the uterine vessels are beautifully exposed and easily caught, only a clumsy operator will plunge his needle or a pair of forceps deep down into the tissues and clamp a ureter. By cutting up the cervix so as to leave a snipe on each side the uterine vessels can be caught at a higher level than that of the division of the cervix.


There is no danger of injuring the bladder, which needs less attention than in any other method of hysterectomy; when the bisection reaches the vesico-uterine fold it may bo continued carefully behind this fold well down into the cervix under the bladder which is then easily pushed down as the divided cervix is pulled apart. A simple and a safe way is also to incise the vesico-iiterine peritoneum from side to side and push it down with a sponge on a staff and so bare the cervix.

If the uterus is densely adherent to the rectum all the way up to the fundus, a modification of this plan of operating may be followed; the anterior face of the uterus may be bisected and the cervix divided horizontally and the uterine vessels caught, then the rest of the uterus may be carefully divided up its posterior surface in a direction from the cervix towards the fundus. The relations to the rectum are examined as the division is made, and at any point where it seems nccessar)', a piece of the uterine tissue may be left adherent to the bowel. After the bisection the rest of the enucleation is effected as described above.

I have had abundant opportunity to demonstrate the practical value of this method of treatment in my clinic this year.

In one case (Ward H, 12 April, 1900) the uterus, tubes and ovaries were so densely adherent that an effort to free them by the vaginal route failed when I opened the abdomen and caught the uterus by its eornua and bisected it half way down the cervix, and then removed each half uterine body, then with a maximum space under sight and touch the tubes and ovaries were dissected out.

In another instance (W., 5 May, 1900) the entire uterus was bisected and removed and after its removal a large pelvic abscess was extirpated on the right side.

In a case operated upon 7 Nov., 1900 (W., H) the sigmoid on the left and the rectum on the right were the seat of fistulous openings into the uterine tubes. Here the fistulse and other complications did not have to be treated until the uterus was divided and brought out into the surface.

Another patient in my private hospital had tubercular disease of both tubes (S., April, 1900), which was extirpated with bisection of the uterus.

In one instance (B., 17 Oct., 1900) there were extensive hematomata of both ovaries with dense adhesions and a most difficult enucleation was rendered safe by bisection.

In a case of a large cancerous right ovary (B., l9 May, 1900), extending into the pelvic cellular tissue, I found a bisection most helpful in clearing out the pelvis and exposing the disease on its median and under sides, and so making possible a much completer enucleation.

The dangers of the method are those of any novel procedure, and must arise for the most part from want of due attention to the details; for example, one can by reckless cutting divide the uterus obliquely so as to cut directly' into the broad ligament among the uterine vessels instead of following the uterine canal and making a true coronal section. Again, rashly cutting, one can divide one-half of the cervix and divide the uterine vessels at the same time with frightful hemorrhage; by clamping the bleeding uterine


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 118.


vessels in an indiscriminate fashion the nreter may be easily included in the clamp.

I suppose, too, that it is easily possible with sufficient carelessness to cut a hole in the bladder.

The risk of sepsis from opening the uterine cavity is practically nil if gauze is packed in around the uterus; furthermore the study of many of these uteri has shown that the infection rarely ever lingers in its cavity.

The advantages of a bisection and enucleation of the uterus as a preliminary to a complete enucleation of uterine tubes and ovaries for pelvic inflammatory and other diseases by the abdominal route are briefly recapitulated:

1. Additional space for handling adherent adnexte, afforded by the removal of the uterus.

2. Great increase in facility for dealing with intestinal complications.

3. Better access by new avenues from below and in front to adherent lateral structures.


4. Elevation of structures to or above pelvic brim or even out into the abdomen, bringing them within easy reach of manipulation and dissection.

5. The same advantage in approaching both uterine vessels by cutting from cervix out towards the broad ligaments as is secured in approaching one of them in the continuous transverse incision method.

In general, the time of the operation is shortened; its steps are conducted with greater precision; siirrounding structures are far less liable to be injured. In this way there are fewer troubles and sequelae and the mortality is lessened.

I take it that in intraligamentary tumors of both sides this procedure will prove of the utmost advantage in exposing the tumors at a point low down in the loose cellular tissue of the broad ligament.

I have found since writing this that a similar plan of operating has been advocated by J. L. Faure of Paris.


ABSTRACT.'


THE BACTERIOLOGY OF CYSTITIS, PYELITIS AND PYELONEPHRITIS IN WOMEN.

By Thomas E. Brown, M. D., Assistant Physician The Johns Hopkins Hospital Dispensarij.


It is only within very recent years that the bacteriological nature of the infections of the urinary tract has been placed upon a firm basis by the work of Eovsing, Melchior, Guyon, Krogius, Schnitzler, Albarran and Halle and others, and there are still many questions regarding this subject which have not been answered, and various contentions which have not been settled.

The objects of my research have been to determine definitely, as far as lay in my power, the bacterial flora of the infections of the urinary tract in women and to clear up, as far as possible, the moot questions in this subject, to discuss the other factors which may play a part in the etiology of such infections and their relative importance in the development of these conditions, to determine the various modes of entrance of the bacteria into the urinary apparatus, to formulate if possible certain rules regarding the relationship between the species of bacterium found and the clinical picture presented, to suggest from these findings the line of therapy to be carried out, and to note carefully any details in the cases, considered both individually and collectively, that might tend to throw light upon the disputed points of this question or to open up new lines of thought and investigation.

The circumstances attending this investigation were extremely favorable. In the first place, an unusual opj^ortunity was furnished for the study of the etiology of these


I The paper in full will appe.<ir in Volume. X, The Johns Hopkins Hospital Reports.


infections as most of the acute cases were post-operative and were most carefully studied before, during and after the infection; in the second place, a careful cystoscopic examination was made in all the chronic and most of the acute eases, so that no possible mistake could be made in the diagnosis of the bladder infections; in the third place, the; urine was obtained directly from the kidneys by ureteral catheterization in all cases of supposed renal infection, and from the urine so obtained the bacteriological, chemical and microscopical investigations were made.

The cystoscopic examinations were made and the ureteral catheterizations were done by Dr. Kelly, whom I wish to thank sincerely for his unfailing kindness in this particular. This work has been carried on during a space of two years and comprises one hundred cases, besides numerous control experiments.

The complete article will be subdivided into the following sections: I. The method of obtaining the urine aseptically;

II. The chemical and microscopical examination of the urine;

III. The bacteriological study of the urine; IV. The cases of acute cystitis; V. The cases of chronic cystitis; VI. The cases of tuberculous cystitis which have been considered separately for obvious reasons; VII. The cases with symptoms suggestive of cystitis but with no infection; VIII. The cases of acute pyelitis and pyelonephritis; IX. The cases of chronic pyelitis and pyelonephritis; X. The cases of tuberculous pyelitis and pyelonephritis; XI. A review of the bacteriological, chemical and etiological findings in our series; XII. A short resume of the work of other investi


January, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


5


gators in this field; XIII. Polymorphism and other peculiarities of the micro-organisms met with in our series, with a few observations on the agglutination of the micro-organisms found in cystitis, pyelitis and pyelonephritis by the serum of the patient, and, XIV. A few therapeutic suggestions directly dependent upon the results of the bacteriological and chemical studies. Under section IV will be found a note oa bacteriuria, and under section IX some observations on the relation between calculus and infection.

The number of cases in my series is exactly 100, subdivided as follows: cases of acute cystitis, 26; cases of chronic cystitis, 31 (alone 24, associated with pyelitis 7); eases of tuberculous cystitis, 6 (alone 2, associated with renal tuberculosis 4); cases with S5rmptoms suggestive of cystitis but with no infection, 17 (due to urinary hyperacidity !), due to other causes 8) : cases of acute pyelitis and pyelonephritis, 3 ; cases of chronic pyelitis and pyelonephritis, 13 (alone 4, associated with cystitis 8); cases of tuberculous pyelitis and pyelonephritis, 6 (alone 2, associated with cystitis 4).

It will be obviously impossible in an abstract as short as this to give more than a very brief summary of the most important findings in the various sections mentioned above.

I. The Method of Obtaining the Urine Aseptically FROM Bladder and Kidney.

The following method was employed for obtaining the urine aseptically: From the bladder; the vestibule of the vagina and the mouth of the urethra having been carefully cleansed with bichloride of mercury solution (1:1000) or boracic acid solution (saturated) followed by sterile water, the lips of the urethra are pulled apart by traction on the labia and a sterilized glass catheter with a sterilized rubber cuff, about 10 cm. long, on its distal end is introduced, the operator only touching the rubber cufif at about its middle. After the urine has flow'ed for a short time (so that if a few micro-organisms from the urethra were introduced, they would be washed out by the first-flowing portion of urine), the rubber cuff is withdrawn by traction on its distal end and 10 to 20 ccm. of urine collected in a sterile tube, the cotton ]ilug of which is only removed during the reception of the urine. In obtaining urine from the Mdney, the sterilized rubber cuff is placed upon the distal end of the sterilized ureteral catheter, which is introduced through a cystoscopy into the ureter, great care being taken that it touches nothing in its course until it is inserted into the ureteral orifice. The bladder should be thoroughly washed out Just previous to the procedure if there is the least possibility of a vesical infection being present, while if an infection of the bladder has been definitely determined either by urinary or cystoscopic examination, the ureteral orifice should be carefully swabbed off with a solution of nitrate of silver and the catheter inserted but a short way up the ureter (to prevent any possibility of renal infection from the bladder); as in the case before, the urine should be allowed to flow for a short time before the withdrawal of the rubber cuff and the reception of the urine in the sterile test-tube. Ordinarily the urine flows drop by drop but. in case of pyoureter or


hydroureter, or pyonephrosis or hydronephrosis, the urine first flows in a steady stream for a short time until the dilated portion of the ureter or dilated renal pelvis is emptied, when the catheter reaches that portion of the ureteral or renal tract. The adequacy of these methods has been shown by the negative results obtained in 53 control experiments in the -ease of the bladder and 33 in the case of the kidney.

II. The Chemical and Microscopical Study of the Urine.

After having obtained the urine as described above, it is essential that within a very short time (a few minutes if possible) cultures should be made, as well as a careful chemical and microscopical examination either of this specimen or of a larger quantity obtained by catheter at the same time. The reaction of the urine should be carefully testecT, as by its acidity, neutrality or alkalinity it tells us in a broad way something regarding the nature of the microbe causing the infection. In cases with symptoms of cystitis but with no infection, it is important to determine also the degree of the acidity, which has been done in our cases by titration with a 1-10 normal solution of sodium hydroxide, phenolphthalein being used as the indicator, for, as we shall see later on, urinary hyperacidity may definitely cause symptoms which may easily be mistaken for those of cystitis.

The specific gravity of the urine is of importance because of the frequency of low specific gravities in cases of pyelonephritis and also in cases of hysteria and the various neuroses, and its determination is of especial interest when both kidneys are catheterized, as well as the quantitative determination of the t(7-ea-output from either kidney, so that we may determine the secretory function of each — a question of immense importance when nephrectomy is under consideration.

The dctermiiuition of the quantity of albumin present is of great importance because, combined with a careful cystoscopic examination and a determination of the grade of pyuria and hematuria, it furnishes a valuable criterion for the differentiation between renal and vesical infections. which is of especial value in the hands of those to whom ureteral catheterization is impossible. Of course the urine must be examined shortly after its withdrawal, and considerable experience must have been had in this mode of diagnosis; but, if these requisites have been fulfilled, one may definitely conclude that if the grade of pyuria is decidedly more marked than the grade of albuminuria, cystitis is probably present alone; while, if there is considerable disproportion in the other direction, it speaks for a renal infection, alone or associated with a cystitis. If a person had a chronic nephritis before the development and during the course of the cystitis, the diagnosis would be rendered more difficult, although the presence of casts in this last condition woidd call our attention to this source of error. Obviously, however, the only absolutely satisfactory method to be cmployed is catheterization of the ureters combined with a careful eystoscopic examination.


6


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 118.


The microscopical examination is of value because it tells us of the absence or presence of vesical, ureteral and renal epithelial cells; it calls our attention to the crenation or lack of crenation of the red and white blood-cells (the former of which conditions speaks for a renal hematuria or pyuria if the grade of these conditions is low — if the pyuria or hematuria is of high grade this method of differentiation is of very little value); and it tells us of the morphology, number and motility of the micro-organisms giving rise to the infection. By counting the red and white bloodcells in a definite quantity of mixed urine (1 cmm.) with the Thoma hematocytometer we can definitely determine the success or failure of the mode of treatment employed.

III. The Bacteriological Study of the Ueine.

The methods of making the cultures and identifying the bacteria found are those usually in vogue, two or three loops of urine or of diluted urine being first plated on agar-agar from which transplantations can be made on the various media. The bacilli should also be counted on the plates so that, by studying the cultures taken from the urine from time to time, the success or failure of the method of treatment employed may be definitely determined.

In all cases, except perhaps acute post-operative cases, the tubercle hacilli should be carefully searched for in the sediment, while if there is pyuria or hematuria in an acid urine but with no growth on the ordinary media, intraperitoneal injections into guinea-pigs should also be employed.

In any specimen where the history of the case or the microscopical examination of the sediment makes us suspect the presence of the gonococcus, this micro-organism should be sought for by the use of special media and of special staining reactions.

INFECTIOXS of THE BLADDER.

In our series of cases we have divided the cases of cystitis into acute, chronic and tuberculous, and then subdivided these groups along bacteriological lines. We have considered those cases as acute in which the infection has been present but a short time, where there is no real contraction of the bladder and where there are no distinct areas of ulceration, while in the chronic cases the duration has been longer, there is practically always more or less ulceration, and the bladder is distinctly and usually markedly contracted.

IV. Cases of Acute Cystitis.

These cases are of especial interest because of the fact that, as all but two of the 26 cases studied were post-operative infections, in which the urine had been carefully examined immediately preceding the operation, they furnish us with absolute criteria as to the micro-organisms bringing about the infection and the other etiological factors involved.

In all these cases the micro-organism causing the infection was present in pure culture and generally in large number; in practically all of the cases two and in the rarer ones three or more cultures were made, and in the post-operative cases


a culture was always taken after the disappearance of symptoms; in all these 24 cases the infection entirely disappeared under treatment. The urine in all these acute infections contained varying numbers of pus-cells, red blood-cells and vesical epithelial cells.

The bacteria found in these 26 cases were: B. coli communis 15 times, or 57.7 per cent; staphylococcus pyogenes albus 5 times, or 19.2 per cent; staphylococcus pyogenes aureus twice, or 7.7 per cent, and B. pyocyaneus, B. typhosus and B. proteus vulgaris (of Hauser) once each, or 3.8 per cent, while in one case, microscopically, a colon bacillus was found, although the cultures were not completed.

In all the cases except one — that due to B. proteus vulgaris (where the urine was ammoniacal) —the iirine was acid, although the degree of acidity varied markedly with the variety of micro-organism, being usually increased in the case of the colon bacillus and typhoid bacillus infections, and diminished in the case of the staphylococcus infections, especially in the case of staph3doeoccus pyogenes aureus, where the urine was sometimes neutral in reaction. Especially striking is the prevalence of the colon bacillus and the absolute proof that this micro-organism can by itself give rise to vesical infections as furnished by these studies, while the infections due to the pyocyaneus and typhoid bacilli are of great interest, because of their extreme rarity. These last two cases are reported in full elsewhere {Marijland Medical Journal, 1900, May; Medical Eecord, 1900, March 10).

The time of the development of the symptoms varied between the 3d and the 20th days after the operation, being shorter in the cases of B. proteus, St. pyogenes aureus and some of the infections with B. coli communis. Apparently the more virulent the micro-organism and the more severe the symptoms, the earlier after the operation the infection manifested itself.

The mode of entrance of the bacteria into the bladder in the majority of these cases was undoubtedly from the urethra by catheterization, although this procedure was performed with extreme care, which is not at all remarkable when we consider Melchior's, Savor's, Gawrowsky's, Bouchard and Charrin's researches upon the bacterial flora of the normal urethra and vulva, colon bacilli and various staphylococci being frequently found.

In some cases, however, infection seemed to have taken place definitely from the rectum or from some focus of infection either by means of the blood or lymph currents or by direct transmission.

We were, however, at once struck in considering our cases of acute cystitis by the fact that other accessory etiological factors seemed to be absolutely necessary for the production of the infection in the great majority of these cases, which, so to speak, prepared the bladder for the reception of these germs and rendered it susceptible to their usually low pathogenic power.

The most important of these factors, as evidenced by our series, were anemia and malnutrition, constant pressure on the bladder by other organs or by new growths, sagging of the bladder due to relaxation of the perineum, trauma to


January, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


the bladder either duo to the operation or to the catheterization (these are nndoubtedly the most important of these accessory factors, as evidenced by the fact that in almost all the cases of post-operative cystitis the nature of the operation was such that considerable trauma of the bladder was inevitable), the trauma and congestion of the bladder incidental to child-birth, catheterization with poor technic^ue. and a contiguous focus of infection (a large appendicular abscess in one of our eases). In the case of the urea-splitting micro-organisms (B. proteus vulgaris), the presence of the bacteria plus the irritation of the amnioniacal urine seems sufficient to bring about a cystitis.

No examples of true vesical lackriuria were met with in our cases, but in a few there was seen a condition nearly approaching this, i. e. enormous numbers of bacteria but very few pus-cells in the urine.

V. Cases of Chronic Cystitis (non-tuberculous).

The cases varied markedly in duration and in severity; in some cases the symptoms were comparatively slight, in other cases so severe as to render life practically unbearable. Thirty-one cases in all were studied, in 34 of which cystitis alone was present while in 7 a pyelitis was associated with the cystitis. In 3 of these latter cases the pyelitis had preceded the C3'stitis and in 4 the reverse had taken place; in all the first 3 the vesical symptoms were very slight. In this series of 31 cases B. coli communis was met with 16 times, or 55.2 per cent (15 times in pure culture, once in association with the tubercle bacillus); St. pyogenes aureus 3 times, or 10.3 per cent; St. pyogenes albns twice, or 6.9 per cent; a slowly liquefying (gelatin) urea-decomposing white staphylococcus 4 times, or 13.8 per cent, and B. proteus vulgaris once, or 3.4 per cent. With the exception of the one case mentioned (B. coli and B. tuberculosi), the micro-organisms were always present in pure culture. Of the 31 cases, the urine was acid in 26 (occasionally neutral or exceptionally slightly alkaline in some of the staphylococcus infections), alkaline or amnioniacal in 5 (B. proteus vulgaris, slowly-liquefying ureadecomposing white staphylococcus), although in some of these latter cases, when the bladder infection is very slight and the renal infection marked, the urine may be neutral oi' even acid.

The common modes of infection seemed to have been from the vulva or urethra usually by catheterization, from the rectum, from the kidney, from poor technique in examining or treating the bladder. The other factors in the etiology of the condition were practically the same as in our series of cases of acute cystitis; a new accessory etiological factor is to be found in this series in operations upon the urethra.

VI. Tuberculous Cystitis.

Six cases of tuberculous cystitis were met with in ouiseries. In one case and possibly in another, the cystitis occurred alone; in the other cases it was associated with a tuberculous pyelitis or pyelonephritis. Five of the cases were chronic; one was comparatively acute. The constitutional symptoms and the vesical lesions were marked in all


these cases but one. In all, tubercle bacilli were found, usually in small numbers, occasionally in comparatively large numbers. They were present in pure culture in all but one case, where the colon bacillus was also present (secondary infection after a suprapubic cystotomy). The urine was alwaj's markedly acid and contained usually a large niimber of pus and red blood-cells, the latter being comparatively more frequent than in the other cases of chronic cj'stitis. The mode of entrance of the bacilli was difficult to determine; the bladder seemed to be affected first, probably by metastasis from some tuberculous focus elsewhere in the body. Other etiological factors were difficult to determine; only one case gave a family history of tuberculosis and only one showed a pulmonary lesion; in some cases weakness, anemia and malnutrition seemed to have rendered the bladder susceptible to the infection. In some cases the onset was gradual and insidious, in other cases the symptoms of onset were those of a typical acute cystitis.

VII. Cases avitii Symptoms of Cystitis bttt with no Infection.

Besides the increased frequency of urination, burning sensation, etc., seen after the use of various drugs and in certain neurotic conditions, we have met with two classes of eases with symptoms of cystitis but with no infection. The first class is of especial interest, the symptoms being due to urinarij hyperacidity, which was determined by titrating 10 cem. of freshly drawn urine with one-tenth normal sodium hydroxide solution, phenol-phthalein being used as the indicator. Nine such cases were met with and the acidity of the urine varied from twice to five times the normal. The urine always contained a ievf, and in the more severe cases a moderate number of pus and red blood-cells, while cystoscopic examination usually revealed a markedly ingested trigonum. The condition seems to be one of the manifestations of a general neurosis which requires general as well as local treatment, the latter of which consists mainly in the neutralization of the intense acidity of the urine by the administration of alkalis by mouth. Cultures of the urine were always negative and the condition, so far as I knou-, lias not definitely been described previously. The condition is of especial importance because, if misinterpreted, local applications, irrigations, etc., are frequently inaugurated which, in the hands of all but the most' careful and skillful, frequently lead to vesical infections.

Eight cases with symptoms of cystitis hut with no infection are reported due to other causes; such causes are relaxation of the vaginal outlet, especially if marked anteriorly, retroflexed uterus, pelvic inflammatory disease with vesical adhesions, large pelvic neoplasms pressing upon the bladder, mucous polypi protruding from the vagina, and varicosity of the vesical veins. If the pathological condition is corrected by operation, the vesical symptoms shortly disappear.

pyelitis and pyelonephritis.

These studies are unique in that the urine from which they have been made was obtained directly from the kidney by


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[No. 118.


ureteral catheterization. Both kidneys were usually catheterized, so that the two sides could be compared— a most important point in determining upon the advisability or nonadvisability of nephrectomy.

VIII. Acute Pyelitis and Pyelonepheitis.

Only two cases were met with, in both of which the renal infection was secondarj' to the bladder infection. One was due to B. coli communis and the urine was acid; the other was due to B. proteus vulgaris, and the urine was alkaline. In either case the other kidney was perfectly normal. It was interesting to note that in one of these cases the affected kidney was the one suspended at the operation.

IX. Chronic Pyelitis and Pyelonepheitis

(non-tuberculous) .

Twelve eases of this condition were studied, in 4 of which the pyelitis was present alone, in 8 associated with cystitis. Catheterization of both kidneys showed that the infection was unilateral in all but one case. The symptoms were very variable, being sometimes almost nil, sometimes very severe. The urine from the infected kidney was usually pale, of less specific gravity, increased in amount, low in urea percentage and contained a greater or less number of pus-cells, some red blood-cells and ureteral or renal epithelial cells. The bacteria found in these 12 cases were : B. coli communis G times, or 50 per cent; B. proteus vulgaris 3 times, or 25 per cent;- the slowly-liquefying, urea-decomposing white staphylococcus twice, or 16.7 per cent, while in one case there was no growth, the infection evidently having died out. The urine was acid in the colon bacillus cases, alkaline in the cases due to the other micro-organisms. As to the mode of infection, in 5 the bladder was infected first and the kidney secondaril}', evidently by an ascending ureteral infection, while in 5 and probably in one other the kidney was infected first; that is, the infection was probably carried directly to the kidney by means of the blood or lymph currents ; in one case the infection was an ascending ureteral infection, there being a uretero-vaginal fistula.

An interesting point regarding the relation hettveea infection and calculus formation was to be made out from a study of these cases. In all 5 cases of chronic pyelitis, where the urine was alkaline due to a urea-decomposing micro-organism, a renal calculus composed of phosphates and carbonates of calcium and magnesium was found, while from the centre of one of the calculi a pure culture of the micro-organism causing the pyelitis was obtained.

X. The Cases of Tuberculous Pyelitis and Pyelonephritis.

Six cases of this nature were met with, in 2 of which the renal infection occurred alone, while in the other 4 a vesical infection was associated with it. One of the cases was an acute infection, while 5 were chronic. All eases were pure infections and in all 6 the tubercle bacilli were found in the urine. The urine was always acid, contained considerable albumin, many pus-cells, more red blood-cells


than seen in the other forms of pyelitis, and renal and ureteral epithelial cells. None of the 6 cases gave a tuberculous family history and only one showed a tuberculous lesion outside the urinary tract. In 4 of the cases the kidney seemed to have become infected from the bladder by an ascending ureteral infection.

In the complete article, section XI is devoted to a general consideration of the results obtained, and section XII to a discussion of the bacteriological results obtained by other observers.

Section XIII treats (1) of the polymorphism of various bacteria, especially' as regards variation in cultural peculiarities, motility and virulence of the colon bacilli and the chromogenic properties of the staphylococci, and (2) of the agglutination of the bacteria by the patient's serum in cystitis and pyelitis, a positive reaction being obtained in 2 of the 3 cases tested.

Section XIV deals with a few therapeutic snggestions directly dependent upon the bacteriological findings, the question of treatment not being further discussed in this article, as it obviously belongs more to the surgeon than to the bacteriologist. To render the urine a poorer medium for the growth of bacteria and to help to wash out thu bacteria, pus-cells, etc., present, large quantities of water should be administered, preferably by mouth, but if this is not feasible, by rectal enemata or by subcutaneous injections. The administration of substances which render the urine somewhat antiseptic, as urotropin, cystogen, salol, etc., is advisable, especially in the acute cases. Also in cases associated with an alkaline urine, acids such as boracic, benzoic or camphoric acids should be given by mouth in sufficient quantity to render the urine acid, while in the acid infections alkalis should be given until the urine is alkaline, as it would seem probable that by these means we diminish the growth of the respective micro-organisms by furnishing a less favorable medium. The same condition of inhibition of growth would probably be brought about in any case by the administration of a great excess of either acid or alkali. It is essential that the resisting power of the patient be increased as far as possible by a careful attention to all questions of personal hygiene, the insistence upon plenty of fresh air, sunshine and good food, the removal of depressing or very exciting influences, the attention to any disorders of the blood, the circulatory and respiratory organs or the organs of digestion and elimination if such conditions arc present. Of course, in many cases other measures besides the ones just mentioned have to be employed, such as topical treatment, irrigations, instillations (nitrate of silver has proven of most value to us in these connections), operative treatment of various kinds, etc., and the above are but the suggestions regarding the general medical treatment of cases of cystitis, pyelitis and pyelonephritis derived directly from the bacteriological study of the cases.

Discussion.

Dr. Young.— I have enjoyed this paper and I think Dr. Brown is to be congratulated for his excellent work. My


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9


interest in this subject has extended over several years, as I luive been working, particularly on male subjects, during that tijiie along the same line. In looking over the results obtained I was struck by the gj-eat dissimilarity of the i)i-ganisnis we have found. ]\[y work includes, I thiuk, three or four times as many organisms as have been found in the cases studied among the females. For instance, among others I found all forms of the proteus, the streptococcus, tlic stapliylococcu.s albus and the aureus, the bacillus lactis aerogenes, and, several times, the gonococcus.

Another discrepancy between our results is that the colon bacillus, which occurred in tlie great majority of cases in the female, was not so often found in the male. The staphylococcus pyogenes albus in my cases was found to be a mucli more common cause in the male of acute or chronic cystitis and nephritis.

One particularly interesting point in the jiaper is in regard to the effect of these bacteria upon the urine, as Dr. Brown has mentioned. For instance, in my cases with a pure colon bacillus infection there was always an acid reaction, while with the ijroteus there was a marked alkaline or ammoniacal reaction. If both were present in the same case there was usually only a slight alkalinity, the acid-forming colon bacillus apparently neutralizing more or less completely the alkajinizing effect of the proteus group. In one case I was al)Ie to prognosticate the presence of these two organism^ simply upon the finding of a very slightly alkaline urine with the presence of large numbers of bacilli — enough to have made it strongly acid if colon alone were jiresent, and very alkaline if proteus were the sole organism.

We have encountered a number of sta])hylococci that could not exactly be classified; in fact, there were all grades of staphylococci in the cultures I have examined, some requiring 15 days to liquefy gelatin and some that did not li(pu'fy it at all, and I suspect that Dr. Brown's staphylococci belong to the group that Melchior has called the diplococcus urea; non-liquefaciens.

As to the amount of albunun in making a diagnosis of ]iyelitis from cystitis, I think from practical experience it is often pretty difficidt to determine. Finger, discussing the question of infection of the pelvis of the kidney after gonorrhoea, says that if the albumin has reached 1.5 per cent you can generally safely consider that the pelvis of the kidne\ is involved, but we have noticed in examinations of the urine in cases of cystitis the amount of albumin varied very greatlv, sometimes being present in considerable amount, sometimes entirely absent, with similar amounts of pu< ])resent.

Dr. Brown's case of typhoid infection of tlie bladder is certainly a very interesting one. In the first place, tlir organism was introduced from without; and, secondly, it is the only case I believe in which a careful cystoscopic studx has been made in an acute cystitis due to the bacilhityphosus. The sjTiiptoms in his case were very severe and differ in that respect from the usual cystitides following tyj^hoid fever. In a great majority of cases in which the


bacillus appears in urine after typhoid fever there is no irritation at all. It seems to be the fact that infection of the bladder by the typhoid bacillus is a very mild one in most cases, but I have recently had a case of severe chronic cystitis, with marked ulceration of the mucosa, in which the bacillus typhosus was the sole infecting bacterium, and that seven years after the attack of typhoid fever.

In all the cases infected with the proteus I have had the urine has been strongly alkaline, but we have recently had one case in the hospital that had an acid reaction, and a study of the organism by Dr. Sabin showed it to be the proteus Zenkeri, which is not as pronounced in its effect upon media and is not an alkalinizer; if inoculated into sterile urine it renders it acid. This is interesting in that bacteriologists, I believe, consider all the proteus organisms to belong to one group and to be interchangeable.

Gonococcus infections of the bladder were not present in Dr. Brown's cases, and I believe they are much more common in the male, owing to the greater severity of the urethral inflammation in the latter. Thus I have found this organism six times in the bladder, in three acute and three chronic cases of cystitis. The only other cases jn the literature, however, where cultivations of the gonococcus were obtained, were in the female, the difficulty of obtaining cultures from the bladder of the male in acute gonorrhreal infections being the probable cause. This was overcome in my eases by aspiration of the bladder above the symphysis.

The demonstration of the ease with which the- bladder may bi' aspirated for cultures will probably soon increase the present limited number of observations on the ability of the gonococcus to invade the bladder.

Dii. Welch. — There are only one or two points which I shall undertake to discuss in Dr. Brown's very interesting and important paper. I am impressed by the fact that both Dr. Brown and Dr. Young find that bacteria which have ordinarilyVery limited pathogenic activity and do little harm elsewhei'e in the body are so often concerned in cystitis and pyelitis. This is the more remarkable as it has been demonstrated I hat the healthy bladder is capable of disposing of large nundiers of much more virulent kinds of bacteria. The The slowly-liquefying and the non-liquefying white staphylococci we are accustomed to regard as among the least pathogenic pyogenic cocci, and still these are apjiarently often present in the urine in cystitis and are interpreted as the exciting factors in the causation. This should in my opinion lead us to attach much importance to various accessory causes which render the urinary passages incapable of resisting even these mildly pathogenic bacteria, and it would be a one-sided view which failed to take into consideration in the etiology of cystitis and pyelitis the nonbacterial factors.

The ((uestion has been raised as to the identity of the non-lii|uefying white staphylococcus. I should like to inquire whether the coccus in question may not be Staphylococcus cereus albus. There is every gradation among the pyogenic staphylococci as regards such properties as rapidity


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[No. 118.


and intensity and tint of color-production, liquefaction of gelatin, coagiilation of milk and virulence when tested on animals, so that there is much in favor of the view that the}' are varieties of a common species. We have been in the habit of designating as Staphylococcus epidermidis albus the slowly liquefying and slowly coagulating white staphylococcus, which, moreover, is of limited virulence and, as has been abundantly demonstrated, is a regular inhabitant of the human epidermis. I should infer from Dr. Brown's description that this Staphylococcus epidermidis albus has been often encountered by him in cases of cystitis.

De. Hunner. — I have been struck with the apparent nonrelationship between the degree of bladder disease and the infecting organism which under other conditions is often very virulent. Especially is this true in my experience with the streptococcus.

We had a ease in Dr. Kelly's service last fall who was the wife of a physician and had been under careful observation. Eight weeks before adniission her first sign or symptom of disease appeared in the form of a marked hematuria, the urine being of a claret color and occasionally containing small bright red clots. After three weeks she became anemic, had occasional pains in the right kidney region, and experienced some headache, giddiness, and nausea. There had been no elevation of temperature until two weeks before admission, when she was suddenly taken with a severe shaking chill which lasted one and one-half hours and was followed by a rise of temperature to 104.3° F., violent headache, pains in the legs, retching, vomiting, and great restlessness. The temperature gradually subsided but had reached 100° every afternoon since. The urine was found to contain great numbers of streptococci in pure culture, and a catheterized specimen from the right kidney showed infection by the same organism. Nephrectomy was done and a small stone was found in one calyx with multiple foci of necrosis scat


tered throughout the kidney. The bladder mucosa seemed entirely healthy.

A patient was admitted this spring who had suffered with symptoms of stone in one kidney for the past two years, and in both kidneys for three months past. Streptococci were obtained in pure culture from the bladder and from either kidney, but the bladder mucosa showed no lesion. Waxtipped bougies were scratched by stone in either kidney.

A case came in a day or two ago and from her history stone in the right kidney was suspected. On catheterization of the bladder macroscopically, clear urine was obtained. Cystoscopy revealed a healthy-looking bladder. I catheterized the right kidney with a wax-tipped bougie and obtained scratchmarks from stone. On examination of my plates to-day I was surprised to find a pure growth of streptococcus both from the bladder and the right kidney.

Dr. Brown. — I would like to say that one of- the probable reasons why the bacterial flora in my cases is not so large as in Dr. Young's experience is that my cases were taken entirely from private patients where the chances of infection are decidedly less.

In regard to the disputed staphylococcus, I thought, of course, that it possibly was identical with the diplococcus of Melchior but could not convince myself of it, as it certainly showed no especial tendency to assume the diplococcal arrangement.

As I have stated before, the infections were almost always confined to those cases in which the resistance was very low, or the traumatism of the bladder was marked.

I have not attempted to carefully differentiate the various white staphylococci found in these cases, for it seems almost impossible to satisfactorily separate these micro-organisms into especial groups, as all gradations in cultural peculiarities were met with. As Dr. Welch has stated, some of them certainly could be best considered as Staphylococci epidermidis albi.


THE INTRINSIC BLOODVESSELS OF THE KIDNEY AND THEIR SIGNIFICANCE

IN NEPHROTOMY.


By Max Bbodel.


[PRELIMINARY COMMUNICATION.!]


In view of the enormous number of investigations of the different structures of the kidney recorded in the literature


1 Since this article was sent to press, I learned that Dr. William Keiller, of Galveston, Texas, lias been followiDg a similar line of research. His findings were embodied in a report to the Te.^cas State Med. Soc, in whose Transactions for 1900 they appear. I have just received through the kindness of Dr. Keiller some of his specimens which substantiate many of the points brought forth in this paper, although the methods he employed differed essentially from miue. This being merely a preliminary communication precludes the possibility of discussing in detail Dr. Keiller's excellent work.


it seems strange that only scanty information exists on the actual course of the larger blood-vessels and their relation to the pelvis of the kidney. The normal and abnornuil arrangement of the vessels at the hilum are well known and the microscopical pictures of the vessels in the cortex and pyramids are likewise thoroughly familiar to every student. But as to the actual form of the pelvis and the course and distribution of the larger vessels around its walls very vague ideas still prevail. It is evident that exact knowledge of the anatomy of this region would prove of the utmost im


jANtlARY, 1901.]


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11


portanco to the surgeon in enabling him to open the pelvis of the kidney withont running the risk of cutting largo branches of the renal artery.

In order to study this region I made a large number (40) of celloidin injections of human kidneys. The injected specimens were then digested ' and the casts thus obtained, examined. Nearly thirty additional injected kidncj's were not digested, but were cut into sections in various planes in order to control the results obtained by the method of digestion. Some of these sections were rendered translucent by the usual methods.

I made separate injections of the arteries, of the venous system and of the pelvis, combinations of any two out of three and finally triple injections. The great majority were of the last class. At first I confined my injections to kidneys which seemed normal so far as regarded form and size ; later, after I had, in this way, determined the law according to which the vessels were grouped, I concentrated my attention upon abnormally shaped kidneys. The present paper will contain a short abstract of the main results of these studies. I shall confine myself to the description of the normal form and mention briefly only a few variations. A more elaborate communication will appear later.

The Pelvis of the Kidney. — From a surgical standpoint all forms of pelves may be classified under two main groups.

(1) True pelves with major and minor calices.

(2) Divided pelves, where there is no free communication possible between all of the calices inside of the kidney.

(1) True Pelves. — Fig. 1 shows the ideal form of a true pelvis. There are eight calices; the uppermost (1) and lowest (8) of which may have double papillie. The remaining six calices stand upon the pelvis in a double row; an anterior, irregularly arranged (2, 4, 6) and a posterior, more regular, row (3, 5, 7).

The horizontal axis of the pelvis (Fig. 1 D, a, a') runs from the posterior surface of the kidney obliquely through the organ to the outer third of its anterior surface and the two rows of calices leave this axis at almost equal angles. Tho posterior calices, therefore, point to a line just a little posterior to the lateral convex border of the kidney (&), whib; the anterior calices are directed straight forward into the convex anterior region of the organ (c). This form of the pelvis is, next to the distended pelvis, the most favorable for a surgical incision.


p i! I employed Schieferdecker's corrosion-method, sliglitly modified by

I Mister .and Mall. The procedure was as follows : The vessels and pelvis of the kidney were thoroughly washed out and then dehydrated with alcohol and ether. The arteries, veins and pelvis were then injected with cinnabar, Prussian blue and arsenic preparations of an alcohol and ether solution of celloidin, respectively. The kidney was then placed in a digesting fluid consisting of varying amounts of l-.'AOOO pepsin (Sharp & Dohme) dissolved in 0.3 per cent to 0..5 per cent of HCl. The process of digestion was completed in from three or four days to two weeks. When the substantia propria and the connective tissue of the kidney were completely dissolved, they were washed out with a gentle stream of water, leaving only the casts of the injected vessels and pelvis. The casts were preserved in glycerin to which a few drops of carbolic acid were added.


The great majority of pelves have well defined major calices, with a very narrow lumen, and owing to this condition it is often impossible to gain access to the minor calices and remote pockets through a surgical incision into the pelvis at the site of the hilum. Furthermore, this incision must be short, as there is a constant branch of the renal artery running downward over the posterior surface of the pelvis at the hilum.

The varieties of the ideal form are very nuanerous and will be described in detail in the fuller communication above referred to. All kidneys with a true pelvis have a smooth surface or moderate degree of lobulation, regular outline and, as a rule, a normal blood-supply.

(3) Divided Pelves. — Fig. 2 shows the typical form of a divided pelvis. Comparing it with Fig. 1 one finds that between calices 2, 3 and 4, 5 there is a zone of cortical substance (a), which extends to the hilum. It divides the upper part of the pelvis from the lower, and in the majority of cases the lower portion receives the greater number of calices. Although the number of calices in divided pelves may be eight, they are generally more numerous. In other respects the topography of these pelves is similar to that oi the true pelves. A kidney with a divided pelvis, as a rule, preserves its fcetal lobulations and has an abnormal arterial circulation; the division between the individual sections of the pelvis is generally marked on the surface by an especially deep groove, thus causing the appearance as though there were two separate kidneys, one on top of the other. Frequently they are indeed separate organs as far as their secretory function and their arterial circulation are concerned. The veins, however, collect, as a rule, in one single trunk. These conditions are readily understood by one who is familiar with the different stages of the development of the kidney, with its origin, its ascent from the pelvis to the lumbar region and finally the wandering in of the vessels.

The Benal Artery. — The renal artery divides at the hilum, as a rule, into four to five branches, the distribution of which, in relation to the pelvis, is such that three-fourths of the blood-supply is carried anteriorly, while one-fourth runs posteriorly. The relative size of tlie two systems may occasionally be f : ^, § : i, but rarely ^ : i. The arteries are end-arteries in the strictest sense of the word and the branches of the anterior division never cross over to the posterior side, or vice versa. They do not anastomose with each other.' The plane of division between the two arterial trees is indicated by the axes of the posterior row of calices (see Fig. 1 D 6 and Fig. 3 B arrow).

Fig. 3 B demonstrates this in a schematic way. The sec


3 To Hyrtl apparently is due the credit of having first mentioned the "uatiirliche Theilbarkeit der Siere," by which he means that in a corrosive specimen the two arterial systems are completely separated by the pelvis. He also affirms that this arrangement of the renal arteries is found "without exception in all mammalia from tlie whale to man." [Hyrtl, Topographische Anatomie. Wieu, 1883. Bd. I, pg. 834.] Hyrtl's statement has unfortunately been overlooked and up to this date the text-books on anatomy and surgery make no mention of this anatomical fact, so important to the surgeon.


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[No. lis.


tion is imagined as passing transversely through the midflle of the iiidney, as in the lower diagram in Fig. 1. Tiio artery (a) sends a large branch (a') anteriorly and a small branch (a") posteriorly. Both branches are seen running close to the pelvis and the calices up to the region of the papillse, whence they send off fan-like branches (b) around the pyramids. The anterior branch (»') supplies the wliole of the anterior pyramid (P) and the anterior portion of the posterior pyramid (P'), while the posterior branch (a") supplies only the remaining portion of the posterior pyramid (P'). The arrow indicates the division between the two vascular trees, c represents a section of the long lateral column of cortical substance, which is situated between the anterior and posterior rows of pyramids P and P'.

The greater part of the arterial circulation of the kidney follows this system. The entire region from calices 2 to 7 .has this arrangement. Around the uppermost (1) and lowest (8) calyx, however, the arteries have a somewhat different arrangement (Fig. 4). They are derived from the anterior group of vessels and run either as a single trunk, having a diameter of 2-3 mm., to the base of the major calyx, or divide before they reach the calyx into three branches, I, II, III. Branch I and branch III run courses similar to those of branches a' and a" in Fig. 3 B, i. e. anteriorly and posteriorly to the calyx. It is obvious that their arrangement mustprolong the arterial division, existing in the central portion of the kidney, upward and downward. Branch II may be short, as in Fig. 3 A (upper pole), and vessels coming from branches I and III partially may take its place. Or it may be of considerable length, as in Fig. 5, where it makes a long sweep around the inner border of the pole. Branch II is the one that generally plays the role of the supernumerary artery; it may arise from the renal artery near its aortic origin (Fig. 5 a and 6) or even from the aorta (Fig. 5 c); in the latter case it must be considered a supernumerary artery.

Although separate arteries are found in kidneys with smooth surfaces, they are much more frequently met with in those that have preserved their foetal lobulation. This abnormal arrangement of the arteries is, perhapts, the cause of the persistence of the lobulated form. When he meets with a kidney having a distinctly lobulated form, the operator may expect to find a long hilum with separate arteries and an abnormal renal pelvis.

The further course of the arteries, the irregularities that may occur and to what extent they affect the above described schema, will be dealt with in a fuller communication.

The Renal Vein. — Concerning the veins, I shall here record only a few notes dealing with their more important characteristics.

While there is a complete arterial division in the plane connecting the posterior calices and terminating in the lateral half of the upper and lower calices, the veins follow quite a different arrangement. Around the bases of the pyramids they anastomose and form the familiar venous arches. They unite in large branches that run between the sides of the pyramids and the columns of Bertini to the necks of the calices, where they lie between the pyramid and


the arterial branches. The thickness of these collecting veins accounts for the peculiar lobulated appearance of the base and sides of the pyramids (Fig. (5 B). Around the necks of the calices, both anteriorly and posteriorly, these veins form a second system of anastomoses (Fig. G B &) much shorter and thicker than that at the base of the pyramids {a). This appears as a number of thick loops or rings which fit like a collar around the necks of the calices. Nearly all the collected blood of the posterior region is carried anteriorly through these short thick stems, to join that of the anterior portion at the point indicated by c.

In comparing Figs. 3 and 6 one finds that an incision through the posterior row of calices would avoid all the arteries but would sever six of these collecting veins. As there remain, however, sufficient anastomoses at the upper and lower pole of the kidney, no serious consequence should follow an injury to these veins. The large veins at the hilum are generally described as being in front of the artery. This is, however, only the ease in the neighborhood of the vena cava, while at the hilum and tliroughout the entire kidney the veins are usually situated between the arteries and the pelvis.

The Surface of the Kidnc;/ and its Eelatinn to the Underlying Structures. — If one is thoroughly familiar with the kidney's surface it is a comparatively easy matter to determine the arrangement of the underlying structures; one can map out fairly accurately the position of the pyramids, of the columns of Bertini and of the calices; and as a consequence the position of the plane of arterial division can also be determined. Let us consider briefly the principal landmarks.

The anterior surface (Fig. 7 B) of a normally shaped kidney is convex and has its greatest liromiuejice at tlie lower portion at the point indicated by a. The posterior surface (A) is somewhat flattened. A lateral view of the organ (C) shows this very clearly; there is also rendered visible a depression(?) h'), which indicates the position of the lateral column above referred to, or the line of division between the anterior and posterior rows of pyramids. This depression, however, by no means indicates the division between the arterial systems, as below it is situated the greatest number of large vessels contained in the kidney. This line (& h') is therefore a most important landmark and in every nephrotomy should be thoroughly mapped out. The other depressions on the surface indicate the positions of the marginof the individual pyramids or subdivisions of such.

Fig. 8 shows the same kidney as Fig. 7, with its pyramids and calices schematically drawn. The posterior pyramids (A 3, 5, 7) are long and slender, while the anterior ones (B 2, 4, 6) are more rounded at their base, thicker and do not extend so far laterally as the posterior pyramids. Consequently, the line of division (D 6 and b') between the pyramids leans more towards the anterior surface of the kidney, so that the anterior surface of the organ bulges, while the posterior is flat.

Between the pyramids are the columns of Bertini which carry the larger vessels. Fig. 8 C shows that these columns join in a longitudinal column (b b'), in which all of the largest


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE III.




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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE IV.



Fig. 2. — Left kidney with typical form of a divided iielvis. The two divisions of tlie pelvis are separated by an area of cortical substance {a] extendini: almost to the hilum. As a riih' the upper division is narrow and has fewer calices than the lower. The division between the two branches of the i)elvis is senerally marked on the surface of the kidney by a deep depression.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE V.



Kui. ;;.— TliL- rc-inil iirtLTV :ni(l tlit- ilisti ibiitioii i>f its tiiMiiclies ill relation to tlic pelvis.

.\. Anterior view of a lelt kidney. Tliere Mre I'l main branebes seen euterius; the Kidney siibstanee. Only one of tliese (tbe third) passes posterior to the pelvis at the hilnm, also small arteries coiuiug from the uii|ier ami lower main branebes are seen to pass posterior to tlie iippi-r and lower caliees. All the rest of tbe arteries pass anterior to tbe pelvis and its caliees. Tbe small branebes to tbe eortex of tbe anterior portion of tbe kidney have not been drawn in order that the large branebes and tbe pelvis might appear more distinetlv.


y> o s t



B. Transverse section through the middle of the same kidney seen from above. The anterior branch of the artery supplies about ?.i of the kidney substance while the posterior 1. ranch supplies only '4. Tbe dotted line and arrow indicate tlie plane of arterial division.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE VI.



Fig. 4. — Arraugemeut of the ai-teries at the upper ami lower pole. They eoiiie as sinsjle trunks from the main artery aud run at an ans;le of 4.5° or more upward and downward to the vicinity of the "major ealices, where they divide into three branches. I. Anterior branch. II. Median branch. III. Posterior branch. The anterior and posterior branches are as a rule much lariter than the median.



Fig. 5 Variation of the median branch. Tliis brancli may be larsrer than usual and arise separately from the main artery at

points a and 6, or from the aorta direct (<•). It may be as lar^re as the renal artery itself, in which case it gives otf branches I aud III or more. Such an arrangement of the arteries is as a rule associated with an ahnnrmal form and jiosition of the renal pelvis.


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE VII.



Fig. 6. The renal vein and the relation of its branches to

the pelvis of the kidney.

A. Anterior view of the left kidney. For tlie sake of clearness the small veins of the cortex of the anterior portion of the kidney have been omitted.


B



15. Transverse section seen from above. There is no collecting vein posterior to the pelvis; all tlie veins of the posterior region cross over to the anterior portion between the necks of the minor calioes (b) to .ioin the veins of the anterior region at a point indicated by c


THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE VIII.



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THE JOHNS HOPKINS HOSPITAL BULLETIN. JANUARY. 1901.


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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.


PLATE X.



Fig. 1(1. — I'osteriov view of left kidney, slmwiiii;' inelliod of cxnlciriiii; and opening the pelTJs. Tlie lower diagram indicates the direction of the incision in relation to the papillae of the posterior pyramids.


Fig. !>. — A. Lateral view of left Uidney, showing the location of the most advantageous incision through the parenchyma in kidneys which have a normal arterial arrangement.

(!«' Lateral convex border of kidney.

bh' Position of lateral column of cortical substance containing the vessels.

<rc' Best incision.

B. (le Incorrect direction of ineisii>n. I'x Correct direction of incision.



Fio. 11. — Imaginary transverse section through a kidney similar to Fig. !l B, showing manner of ])lac-ing the mattress sutur-e^.


January, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


13


vessels of the kidney (three-fourths nf the arteries and all of the veins) are found (see also Figs. 3 and 6).

As was said before, in lobulated kidneys this column is indicated as a distinct depression on the surface. Tlie capsule seems thickened along this line and frequently iovm^ a whitish band, to which the perirenal fat a])pears to bo more intimately attached than elsewhere.

Lobulation of varying degrees of distinctness is found in the great majority of cases. The trained eye can detect this lobulation in kidneys which a novice would pronounce perfectly smooth. Should, however, the kidney present not the slightest depression or lobulation, the arrangement of the large stellate veins of the capsule will still serve to sufficiently locate the limits of the pyramids and the position of the important lateral longitudinal column (6 b', Figs. 7 and 8). These veins are found to be more conspicuous and are arranged in rows along the lines where the foetal lobulation has been. (See Fig. 7.)

The Incision and Sithsequenl Suture. — The above described landmarks should suffice to guide the surgeon in making his incision so that the kidney can be readily opened between its anterior and posterior arterial branches.

Fig. 9 A shows the lateral view of the kidney; a a' represents a line showing the lateral convex border; h h' indicates the position of the lateral longitudinal column bearing the large vessels; c c' is the line along which an incision should be made. Diagram B shows the direction in which the knife should pass. An incision through the middle of the kidney {d e), would be inadvisable, inasmuch as it would cut through large vessels in region / and would fail to open the posterior caliees. The proper direction is indicated by c X, the knife remaining in tlie posterior half of the kidne^'. The cut should be made anteriorly to the posterior papilla? (p) in order to avoid severing the collecting tubules of the posterior pyramids. It is advisable to palpate if possible the vessels and the pelvis at the hilum before making the incision, and if their arrangement is found to be normal, ;'. e. the pelvis at the posterior region "of the hilum and the great majority of vessels anterior to the pelvis, then the above described procedure is applicable.

I wish to add a few suggestions as to the incision itseli and also as to the subsequent suture.


A short incision is made into the lowermost posterior calyx if possible by means of blunt dissection (Fig. 1 A 7), and through this incision the pelvis is explored. In a collapsed state of the renal pelvis it may be difficult to enter one calyx. In such cases a moderate distention of the pelvis with sterile water or boric solution will facilitate the procedure considerably. If this short incision does not prove satisfactory, the three caliees (3, 5, 7) should be carefully opened by means of an incision from within to the surface (Fig. 10). A curved knife will best answer this purpose. A glance at Fig. 3 A shows that short transverse incisions through the anterior or posterior parenchyma may produce little hemorrhage, provided they do not come too near the hilum. However, such incisions never open the pelvis satisfactorily.

The arrangement of the vessels in the kidney suggests the mattress suture as best adapted for approximating the two cut surfaces. Simple interrupted sutures almost always tear the tissues and produce an insufficient union. The mattress sutures are placed at right angles, or nearly so, to the large vessels and thus effectively prevent any tearing of the kidney substance. If the bight of the suture be 1^ to 2 cm., no strangulation of kidney substance should result. The sutures should be applied in the manner represented in Fig. 11.

I. The pelvis is approximated with fine catgut sutures (a). These ought to be placed between the caliees and take in only the fat, the outer fibrous coat and the muscular layers. The mucous membrane should not be included.

II. The second system of sutures should also be of catgut and should unite the region of the papillae. They should bo mattress sutures (Fig. 11 6) and are best placed by means of a long straight three-cornered needle with a blunt point, so that no injury to the large vessels results. A possible oozing would only serve to tighten the grip of these sutures and thus render them more effective.

III. The third system of catgut sutures should also be mattress sutures and be placed parallel to the second through the cortex near the bases of the pyramids (Fig. 11 c). Occasionally the third system of sutures is superfluous.

IV. The capsule is then closed in the usual manner (Fig. lid).


NOTES ON AEROBIC SPORE-BEARING BACILLI.

By W. W. Ford, M. D., D. P. H., Felloiv in Pathology, McGill University. Montreal.


{From the Mnhnn Pathological Laboratonj.)


The presence of spore-bearing bacilli in the contents of the intestinal tract — in the normal organs and in various serous exudates — is of fairly frequent occurrence in routine bacteriological investigation, but the identification of such micro-organisms does not always present that ease which is requisite for the convenience of the routine worker.


Aside from the well-known forms of Bacillus subtilis and Bacillus mesentericus, other varieties of spore-bearing bacilli are recognized with difficulty, owing to the inadequate descriptions usually found in text-books devoted to bacteriology, where the pathogenic bacteria naturally receive the greatest attention.


14


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 118.


During the past year a number of such forms have been isolated and studied in the Molson Pathological Laboratory and an attempt has been made to group these forms together, using as a basis of classification the table of constant characters recently adopted by Fuller and Johnson.

The various reactions of these bacilli on the usual culture media have been estimated in so far as possible with reference to the possession, or lack of possession, of any of these constant characters, and the results of this study are embodied in the chart which accompanies this paper. Some varieties here described may be identical with bacilli already referred to in the literature, but an attempt to recognize them positively has not met with success, and on this account they have been looked upon as either new species or new varieties of old species.

While such a description as this may at first seem inadequate, experience has shown that morphology alone fails to reveal the identity of our ordinary micro-organisms and that such a chart, as the one here utilized for bacteriological protocols, is of the greatest assistance in species differentiation.

These spore-bearing bacilli were isolated at various times in the laboratory under the ordinary conditions of aerobic cultivation and are purely aerobic or facultative anaerobes in character. They may be divided into two groups — pathogenic and non-pathogenic — in each group being included here five different varieties. The criterion of pathogenicity is in all cases determined by the intraperitoneal inoculation of a mouse with a 1 ce. dose of a 24-hour old culture of the bacillus in question.

The members of both groups grow with ease on the routine culture media, the production of spores taking place rapidly under the usual conditions, a greater abundance of spores naturally being observed on the older cultivations. These bacilli possess certain characters in common: The carbohydrates are never fermented with the production of gas; milk is coagulated, probably by the action of enzymes, as tli. reaction remains neutral or alkaline until after the digestion of the casein when a small amount of acid is produced. The liquefying powers of these bacilli are especially well marked, often casein, gelatin and blood serum alike being affected.

While the correlation of different biological properties in bacteriology has as yet met with rather indifferent success, yet it is a significant fact that marked liquefying powers are often associated with the capacity of spore-formation. Similar deductions cannot be drawn with regard to motility, which occurs, one might say, almost at random and cannot be associated with other characters, as for example, pathogenicity.

The growth on potato is usually very abundant, this growth serving at times as a diagnostic feature. The present status of our knowledge of the conditions under which indol and a faecal odor are produced, does not permit any reliable data to be drawn from these reactions, but their importance, when given, renders their careful study necessary.

Under Group 1, pathogenic spore-bearing bacilli, have been included five different varieties:

Bacillus 4 is a capsulated bacillus which bears some re


semblance to Bacillus mucosse capsulatus, but differs in so many reactions, especially in its capacity to form spores, that it has been placed in this group. It was isolated from the liver of a healthy rabbit. Its morphology is that of long rods with square-cut ends in fresh cultures, the bacillus appearing singly or in short chains. In old citltures it loses its characteristic form, appearing as chains of short oval bacilli with the phenomenon of polar staining especially well marked, two small retractile granules being seen at either end of each individual. The capsule is apparent with all dyes, hut it is most readily observed when the bacillus is found in the tissues of an inoculated animal when the organism itself appears in its original character as a long straight bacillus staining deeply and regularly throughout.

Bacillus A is non-motile, forms a characteristic scum on fluid media, liquefies gelatine, coagulates milk without acidifying or digesting the casein. It is pathogenic to mice, guinea-pigs and rabbits, all of which died in from 24 hours to 10 days, revealing at autopsy no special appearances beyond those seen in infections in general and furnishing pure cultures of the bacillus from the internal organs.

Old cultures of this bacillus — from which, by the way, a peculiar sickening odor is obtained — will kill even as large animals as rabbits in two hours, the animals dying with all the symptoms of profound toxsemia.

Bacillus B was obtained from the kidney of a healthy rabbit and in its morphology is not unlike the preceding variety. It is a long bacillus with square-cut ends — without a capsule — in old cultures growing out into degenerate forms, showing the greatest diversity in morphology. Spore-formation occurs with great rapidity.

Bacillus B is non-motile and does not form a scum on broth, liquefies gelatin, coagulates milk, digesting the casein and producing an acid reaction. It is pathogenic to mice and guinea-pigs, which survive from 24 to 72 hours, but is not pathogenic to rabbits.

Bacillus C was obtained from the same kidney which furnished the cultures of Bacillus B. It is a long, narrow liacillus witli rounded ends, quite regular in shape and maintaining its regularity even in old cultures. Its growth is. somewhat slower than most of the spore-bearing forms.

It is actively motile in 24-hour old cultures, forms a pellicle on broth, liquefies gelatin and blood serum, coagulates milk and digests the casein with the production of an acid reaction. It is pathogenic to mice, guinea-pigs and rabbits, the animals succumbing in from one to three days, and showing the presence of the bacillus in large numlicrs in all of the internal organs.

Bacillus D was obtained from a rabbifs kidney. It is a long, thick bacillus growing at times in short chains; it exhibits polar staining to a marked extent, peculiar unstained areas often being visible in the bodies of the bacilli.

It is actively motile, liquefies gelatin, casein and blood serum, but does not produce acid or coagulate milk. It is pathogenic to mice and guinea-pigs, these animals dying after a lapse of from 12 to 15 days, the characteristic organism being then obtained f ron^ the different organs.


January, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


15


Bacillvs E is a large bacillus obtained by Dr. Yates from a pleural exudate, which in its morphology cannot be positively distinguished from the preceding forms. Its varied reactions on culture media testify to its originality. It grows as a pellicle of broth, liquefies gelatin but not blood serum, and coagulates milk, digesting the casein. Mice are killed by intraperitoneal inoculation in from 3 to 4 days.

Prototypes of spore-bearing bacilli which are non-pathogenic are Bacillus mesenterieus and Bacillus subtilis —bacilli which are jirobably the most common forms of laboratory contamination. For completeness in the chart the reaction? of these bacilli have been either estimated or adopted from Fuller and Johnson. With these, however, may be grouped three other bacilli:

Bacillus F was obtained from the liver of a guinea-pig. It is a thick, plump bacillus, at times in short chains, regular and deeply staining. In its morphology it is somewhat similar to mesenterieus but is rather smaller than the potato bacillus, from which it ditfers, moreover, in not forming a wrinkled growth on agar nor a pellicle on broth, and in not growing in the closed arm of the fermentation-tube nor producing a faecal odor.

Bacillus G, isolated from the stomach contents of an autopsy subject, is evidently a variety of Bacillus mesenterieus which it closely resembles in morphology but is distinguished by liquefying only gelatin and casein, not bloo.l' serum, and by its failure to give a characteristic growth on


potato.


The last member of this group, Barillus II, was obtained by Dr. Nicholls from the liver of a healthy cat. It is the only one of this group which is non-motile and is distinguished from the other members by not forming a scum on broth, in not causing a wrinkled growth on agar and in not growing in the closed arm of the fermentation-tube. It liquefies gelatin and blood serum, coagulates milk, digesting the casein and producing an acid reaction.

It is hoped that this plan of description of bacteria may prove of value to observers in different laboratories, and should its adoption be brought about in different universities, a considerable advance can be made in settling the complex problems of species differentiation.

Note: — Several of the bacteria here described are said to be facultative anaerobes in character but without the capacity of growing' in the closed arm of the fermentation-tube. The latter reaction has been utilized as a criterion of anaerobic j^rowth by a number of observers, it being maintained that the growth of the organism will exhaust the oxygen from the open bulb leaving an o.xygen free medium in the closed arm, in which the facultative anaerobes will always grow. This apparent contradiction in reaction is difficult of explanation unless one considers that certain bacilli, aerobic and facultative iiuaerobes in character, grow with greater avidity in a medium which has free access to oxygen thus being attracted to the open bulb of the fermentation-tube, where they grow luxuriantly, yet nevertheless being capable of development in an atmosphere devoid of this substance, as is proved by cultivation in conditions suitable for anaerobic growth. Compare in this connection the chart of Fuller and Johnson where the Bacillus annulatus of Wright is described as a facultative anaerobe and yet failing to grow in the closed arm of the fermentation tube.











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16


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 118.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Simon Flexnee, M. D. Nature and Distribution of the New Tissue in Cirrhosis of the Liver. — University Medical Magazine, November, 1900.

Andrew H. Whiteidge, M. D. Eeport of a Case of Tetanus with Eeeovery. — Philadelphia Medical Journal, October 20, 1900.

William W. Foed, M. D. Venous Thrombosis in Heart Disease. — Philadelphia Medical Journal, November 17, 1900.

William Sydney Thayee, M. D. Observations on the Blood in Typhoid Fever. — Journal of the Bodon Society of Medical Sciences, Vol 5, No. 1, 1900.

RoBEET L. Kandolpii, It. D. Ossification of the Choroid Leads to the Identification of the Body in an Insurance Case. — Journal of the American Medical As.^ociation, November 10, 1900.

HuNTEE RoBB, M. D. Jlemarks upon the Post-Operative Treatment; with Especial Reference to the Drugs Employed in 114 Consecutive, Uuselected Abdominal Sections without a Death. — Cleveland Medical Gazette, October, 1900.

Adelaide Dutcher. Where the Dnnger Lies in Tuberculosis. — Philadelphia Medical Journal, December 1, 1900.

William Osler, M. D. On the Study of Tubennilosis.— Philadelphia Medical Journal, December 1, 1900.

J. Hall Pleasants, M. D. A Case of Acromegaly in a Negro Associated with a Low Grade oE Giantism. — Maryland Medical Journal, December, 1900.

Andeew H. Whiteidge, M. D. The Importance of Instruction in Medical Schools upon the Modification of Milk for Prescription Feeding. — Maryland Medical Journal, December, 1900.

Thomas R. Brown, M. D. A Review of Some of tlic Recent Work on the Physiology and Pathology of the Blood. — Maryland Medical Journal, December, 1900.

J. H. Mason Knox, Ph. D., M. D. Compression of the Ureters by Myomata Uteri. — The American Journal of Obstetrics, September and October, 1900.

Twenty-five cases are collected from the literature and the gynecolog-ical records of the Johns Hopkins Hospital in which myomata uteri were found to have exerted more or less pressure upon one or both \ireters. The small number of such cases reported is probably due to the fact that moderate grades of ureteral compression from this cause produce few definite symptoms and the condition is consequently overlooked.

The cases are gathered in several groups according to the severity of the ureteral and renal involvement; thus:

Group A. — Moderate ureteral involvement, 8 cases.

Group B. — I'ronounced ureteral pressure, 5 cases.


Group C. — Mechanical destruction of renal substance, 1 case. Group D. — Ureteral pressure with inflammation, associated with

a. Chronic nephritis, 2 cases.

6. Congenital cystic kidneys, 1 case.

C. Pyogenic infection, 2 cases.

d. Pyogenic infection, severe, '■> cases.

e. Kidney, a pus sac, 3 cases.

The several important features suggested by analysis of the cases are then discussed. It is found that this ureteral complication during- the growth of a myomatous uterus occurs usually at middle life, that the tumor mass is usually large in size and firm in consistency, and that although the pressure upon the ureter can be exerted at any point or along much of its course, the most frequent seat for compression is at the pelvic brim. Of the complications the formation of adhesions which often render operative interference difficult and the secondary infection of the urinary tract are most important. The pathology of the condition is brietiy referred to, l)eginning with simple dilatation of the ureters and renal pelvis and progressing, unless relieved, to extreme grades of hydroureter and hydronephrosis, or if the element of infection is added to, pyoureter and pyelonephrosis. There are but few definite signs or symptoms of the condition other than a partial retention of the urine in advanced cases. Hence the diagnosis must be made by a careful direct examination bimanually and with the cjstoscope through which the ureters can be catheterized when their involvement is suspected.

Three lines of treatment are suggested: ((/) expectant, applicable when the ureteral symptoms are slight and give no discomfort to the patient; (6) palliative, permissible only when the ureteral compression is moderate and is not becoming worse or when the condition of the patient is so alarming as not to tolerate a more radical method; (c) radical, that is, the removal of the compressing- mass. This should be undertaken unless contraiudicated whejiever there is definite indication that the ureters are markedly compressed. The following conclusions are drawn:

1. That some compression of the ureter is produced by a large proportion of all large myomatous uteri.

2. The resulting liydroureter and hydronephrosis may continue for years and give rise to no discomfort to the patient.

3. The presence of a dilatation of the ureter and reiuil pelvis however slight, lowers the resistance of these organs to toxic and infectious agents, and hence infiammatory conditions of the ureters and kidneys not infrequently follow ureteral compression.

4. This being the case in all instances of uterine myomata, the possibility of ureteral involvement must be considered. When such a condition is suspected every effort should be made by means of direct examination, by ureteral catheter, etc., to arrive at an accurate diagnosis.

5. Exploratory incision is occa.sionally justified to establish a diagnosis.

6. The ureters should be inspected whenever the abdomen is opened for the removal of the tumor.

7. A myomatous mass found to be exerting undue pressure upon one or both ureters should be removed, if possible, unless operative interference is contraiudicated.

8. Such serious sequelae of ureteral compression as extreme hydronephrosis, pyelonephrosis, etc., should receive appropriate treatment.

The references to the cases aud a table are appended.


PROCEEDINGS OF SOCIETIES.

Vol. Xll.-No. 119.

BALTIMORE, FEBRUARY. !90l.

Contents - February

  • Preliminary Note of a Case of Infection with Balautidium Coli (Stein). By Richard P. Strong, M. D., and W. E. Musgrave, M. D., 31
  • Hyperextension as an Essential in the Correction of the Deformity of Pott's Disease, with the Presentation of Original Methods. By R. TuNSTALL Taylor, B. A., M.D., . . '.' 33
  • Two Examples of Bence Jones' Albumosuria Associated with Multiple Myeloma. By Louis P. Hamburger, M. D., . . . 38
  • Report of a Case of Fulminating Hemorrhagic Infection due to an Organism of the Bacillus Mucosus Capsulatus Group. By George BLnMEE, M. D., and Arthur T. Laird, M. D., ... 45
  • Introductory Note to Drs. Durham and Myers's Report. By William H. Welch, M. D 4S
  • Abstract of Interim Report on Yellow Fever by the Yellow Fever Commission of the Liverpool School of Tropical Medicine. By Herbert E. Durham, and the late Walter Myers, .... 48
  • Summaries or Titles of Papers by Members of tlie Hospital and Medical School Stall' Appearing Elsewhere than in the Bulletin, 4i)

Notes on New Books, 50


PRELIMINARY NOTE OF A CASE OF INFECTION WITH BALANTIDIUM COLI (STEIN).

By' Eichakd p. Strong, M. D., Assistant Surgeon, U. S. A., Director of the Army Pathological Lahoralorij, Manila.

AND

W. E. Musgrave, M. D., Hospital Steward, U. S. A., Resident Pathologist to the First lieserve Hospital.

(From the Army Falholoijkal Laboratory, Manila, P. I.)


Balantidium coli (Steiu), (Paramecium coli — Malmsten) was probably first observed by Leeuwenhoek. In a diarrhoea of considerable duration, he examined his own stools and recognized in them small motile animals, which, he stated, were about the size of red blood-corpuscles, and moved by means of small " f ussartig " formations.

Lenekart intimated that the size of the parasite, as given by Leeuwenhoek, probably rested on a guess, as the latter author was not able to notice any flagella with the microscope of his time.

Malmsten,' in 1857, in Stockholm, first described the par


' Malmsten: Infusorien als Intestinal-Thiere beim Menschen. Virchow's Archiv, Bd. sii, p. 302.


asite in a patient who, for two years following a case of cholera, had suffered at first from digestive troubles and later from a painful diarrhoea. On examination of the patient he found, about an inch above the anus, a small wound, which excreted a thin, bloody pus. A great number of the parasites were constantly found in this discharge and also in the intestinal mucus and freces. The condition of the patient improved considerably with the decrease in the number of the parasites. Lowen classified these parasites as belonging to the genus Paramecium.

In a second case Malmsten found the parasite in the bloody pus-like excretions of a woman suffering from a severe intestinal catal-rh. The woman died. At necropsy, he states, the parasites were found on the healthy mucous membrane


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of the cfEcum and in the vermiform apipendix. They were, however^ missing entirely in the small intestine. In small numbers they were found in the ulcers of the large intestine.

In 1862 Stein proposed the name Balantidinm eoli for the parasite.

In 1891 Mitter ' was able to collect from the literature twenty-eight cases of infection with this parasite. Since this date, De la Chappelle ' (1896), has reported two other eases in man. The article of this latter author is not at hand.

Henschen especially emphasizes the pathological importance of this parasite, but other authors are inclined to the belief that its presence should only be considered as an accidental, unimportant complication. The latter view is the one which is generally expressed in our recent text-books regarding this parasite. Thus Opic ' (1900), in his article on Protozoa, concludes that Balantidinm coli is apparently an accidental parasite which finds favorable conditions for growth in the diseased intestine and that it is improbable that the organism is the etiological factor in the production of the diarrhoea with which it is associated.

We wish to contribute another case to the literatiire of infection with this parasite.

The patient observed by us had lived in northern New England and came to the Philippine Islands in December, 1899. There was no history of previous diarrhoea. He stated that he had been perfectly well until April, 1900, when he began to have diarrhoea which continually grew worse. He entered the hospital here on June 9. From this date up to the time of his death, August 11, he had continuous, uncheckable, severe diarrhoea.

He became extremely emaciated before his death. During life, the blood-examination showed a relative increase in the number of the cosinophiles. The stools showed large numbers of flagellate infusoria measuring from 70// to 110/ilong by 60 to 72 « broad. The periphery is covered with fine actively motile cilia. At the anterior end is a funnel-shaped entrance which is surrounded by cilia and when the parasite is moving, gives the appearance of a


'Mitter: Beitrag zur Kenntuiss des Balnnt. coli. Inaiig. Diss., Kiel 1801.

^ De la Chapelle : Finska lak.-sallsk. liandl., Ilelsiugfors, 1S90; xxxviii, 1041.

■• Opie : Twentieth Century Practice of Medicine, vol. six, 1900.


paddle-wheel revolving. An ectosarc and endosarc may be distinguished, and the parasite possesses the power to change its shape and may appear quite round. The endosarc contains a large somewhat kidney-shaped nucleus and two contractile vacuoles. The surface is lightly striated longitudinally. In the posterior end is an anus from which particles were observed, at times, to pass. The anterior end is more pointed than the posterior and more tapering. For some days before death, each drop of the patient's fasces, placed beneath a cover-glass, contained between 100 and 200 of these infusoria. The stools contained no other parasites, but mucus, blood and epithelial cells were present.

At necropsy, in the lower portion of the jejunum and ileum the mucosa was reddened and contained considerable mucus. In the large intestine the mucosa throughout was covered with bloody mucus which was easily washed off; beneath this layer the mucosa itself was very much reddened. There were a number of shallow ulcerations present in the mucosa whose edges were not undermined; their bases and margins had a blackish pigmented appearance.

Agar plate cultures from the heart, spleen, liver and kidneys were negative for organisms.

Sections of the large intestine stained in hematoxylin and eosin show Balantidinm coli all through the mucosa and passing through the mnscularis and submueosa; some of the sections show the parasites lying along the intermuscvdar septa of connective tissue and penetrating for a short distance between the muscular layers. There is an extensive eosinophilia in the mucosa, muscularis mucosa, submueosa and lymph follicles. The process seems more marked in the submueosa. The mucosa shows areas of necrosis and of hiemorrhage, with cellular infiltrations and desquamation of cells. In the submueosa there are also infiltrations of round cells; the vessels are injected and often about the veins which contain the parasites small hsemorrhages have occurred. The lymph follicles are swollen. The liver shows small areas composed of round cells.

We cannot regard this parasite as a harmless one, for we could not explain the persistent diarrhoea of our patient without regarding it as the exciting cause, nor were we, from the lesions found at necropsy, enabled to explain his death in another way. A complete report of this case will appear shortly. October 4, 1900.


HYPEREXTENSION AS AN ESSENTIAL IN THE CORRECTION OF THE DEFORMITY OF POTT'S DISEASE, WITH THE PRESENTATION OF ORIGINAL METHODS/

By p. Tunstall Taylor, B. A., M. D., Surgeon to the Hospital for Crippled Children, Baltimore; Fellow of the American Orthopedic Association, etc.


Any successful treatment of tuljcn-ular spondylitis must be based on a careful consideration of the anatomical, patho


' Read, in part, at the Fourteenth Annual Meeting of the American Orthopedic Association, on May 13, 1900, Washington, D. C.


logical and mechanical problems involved, and any method determined on must stand the test of clinical experience before acceptance.

Let us first consider briefly some of the chief anatomical features of the spine from the standpoint of the mechanics


Februaet, 1901.]


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33


in the causation and in the treatment of this tubercular osteitis of the vertebrje.

The vertebral column as a whole consists of four curves when viewed laterally — a convexity forward in the cervical region, a convexity backward in the dorsal region, a convexity again forward in the lumbar region and backward in the sacral.

The three first-mentioned curves, with which we are only concerned, are subject to variations dependent on whether llie individual is standing or sitting, and also whether the observation is made on rising in the morning or late in the evening, being in the latter cases more marked.

It has been shown by Brackett ' that recumbency in a prone position lessens these curves, and supine recumbency has been used from time immenunial as an efficient means of treating spinal curvatures.

Suspension by the liead and hands also renders these physiological curves, if we may so designate them, less appreciable. Le Vacher " demonstrated this in 1768 in his " L'arbor suspendens " attached to a corset.

The " jury-mast," for which Lee ' gives the credit to J. K. Mitchell in 182t), and Lee's own " self-suspension spinal swing," devised in 1866, confirmed this observation. We know now, however, that these physiological curves are chiefly lessened by suspension and not the curves due to tubercular disease as the earlier observers thought.

In the erect posture the spine must bear the superincumbent weight of the head, and by means of the ribs and diaphragm also the weight of the thoracic viscera, and, to a (•(>rtain extent, the liver and other abdominal organs. Further, through the sternal attachments of the shoulder girdle and the anterior situation of the arms, there is to a certain extent also, a drag downward and forward on the dorsal sjiine by tliem.

If the spine, as a whole, is viewed in jjrofde in either a skeleton or a fresh specimen, it will be seen that a vertical line drawn througli the liodies of the cervical vertebra' will pass anterior to the dorsal vertebra\ not touching them, but in the lumbar region sucli a line will again reach the vertel)ral bodies. Thus, from an anatomical standpoint, we may lonclude that the meclianics of the spinal column decidedly ])redispose to a ilnrsnl convexity, or kyphosis, even without the addition of disease, which the continuity of the vertebral bodies and interverbral fibrocartilages antagonize anteriorly, and the ligamenta flava, inter- and supraspinalia posteriorly.

Secondly. — From the pathological findings in caries of tlie vertebra?, since the time of Sir Percival Pott (1779), observers have noted that the less compact bodies of the vertebrfB are the seat of the tubercular osteitis, softening and disintegration and not the denser articular and transverse processes, as a rule. As a result of this in tintreated, maltreated and neglected cases, the cliaracteristic deformity


'Bradford and Lovett, Orthopedic Surgery, 3d edition, 1899, ."JS. 3 Memoirs de I'Aciidemie royale de cliirurgie, Paris, 17G8, tome (4). ■•Transactions American Orthopedic Assoc, vol. iv, 244.


has occurred, i. e., the superior and inferior edges of the bodies of the involved vertebra; have come into closer contact anteriorly and the spinous processes are more widely separated than is normal (Fig. 1). In addition, unless means are adopted to cheek this, the healthy vertebral bodies will come into contact with those diseased, and from the traumatic irritation jiroduced thereby and the contiguity, the healthy vertebrre will also become involved in the process and so the diseased area will extend.

What, then, can we gather from this, as the indication for the treatment to combat this normal and pathological tendency to kyphosis? Manifestly it is the nuxintenance of hyperextension of the spine until all danger of extension of the tubercular process is passed and firm cicatrization has occurred from the layer of non-tubercular granulation tissue, which is converted in time into fibrous tissue, cartilage or bone and locks the vertebral bodies or processes together inseparably by ankylosis.

I have illustrated this diagrainmatically (Fig. 2): Let Fig. 2A represent two healthy vertebrae seen in profile. The parallel lines represent the superior and inferior planes of those bodies. The centre of gravity or weight-bearing line is indicated by the dotted line, seen to pass through the centre of the vertebral bodies. The alignment of the spinous processes is seen to be straight.

In Fig. 2B we see the result of an untreated tubercular process where the bodies have collapsed, the planes of the superior and inferior surfaces converge and meet anterior to the vertebral column and the spinous processes are widely separated. The centre of gravity line is thrown further forward, tending to increase the deformity. The separation of the spinous processes shows the characteristic contour of the hump-back.

In Fig. 2C is shown what should be the aim of treatment; the separation of the vertebral bodies as far as the ligamentous and muscular attachments will permit; the throwing of the centre of gravity back on the articular processes and the crowding together of the spinous processes. We cannot say that a true separation of the vertebral bodies really occurs by hyperextension before extensive bone destruction has taken jilace, Init certainly intravertebral pressure is lessened on the bodies thereby. On the other hand, Bradford and Cotton's experiments lead us to suppose in extensive unhealed disease sucli a separation certainly occura in hyperextension.

To meet this aim of treatment, in the latter part of 1891 I presented before the Johns Hopkins Medical Society ° what I termed an api)aratus for applying plaster jackets on the plaster jacket stool on wliicli the patient sat, with the pelvis fixed, the arms extended upwards and backwards, and traction was made on the head by means of a head-sling. The result of this attitude on the spine was lordosis. In that paper, as far as I can find out in the literature, T first called


5 Boston Med. and Surg. Jour., Sept. 30, lilOO, 370-28(1. S.Johns Hopkins Bulletin, No. 4"), February, 180.5, and Medical News, March 2;i, 1895.


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[No. 119.


attention to and demonstrated clinically the importance of extending the spine backwards (hyperextension) and the maintenance of this position by means of plaster of Paris jackets for the prevention or correction of tlie natural tendency of the deformity of Pott's Disease (Fig. 3). However, Hadra in 1891 suggested the same principle by wiring the spinous processes together, " thereby relieving the vertebral bodies," but in the article it is stated he lias not done this operation in Pott's Disease.' Other methods to accomplish the same end were published by otlier observers shortly after.

Chipault published on March 9, 1895, his method of wiring the spinous and transverse processes in Pott's Disease after " forcible correction " of the deformity under anoesthesia by manual traction on the head and extremities and pressure on the gibbosity.*

Calot published a paper on similar operations in 1896.'

Goldthwait reported, ih 1898, his and Metzger's excellent method of hyperextension, without anfesthesia, in which the patient lies supine on two strips of steel, that portion of the spine above the knuckle being unsupported and gravity acting as the correcting force."

Eedard in the same year published his method of mechanical traction in a prone position with anaesthesia and manual pressure on the boss."

In 1899 I presented to the American Orthopedic Association " my plaster jacket stool, supplemented with a pressure rod (Fig. 4), to control the point at which hyperextension was to be made (viz., at the kyphosis) and called the apparatus " The Kyphotone " (^ycsoc, hunchback, and rei-y^r^, to extend). I found that without pressure on the knuckle in mid-dorsal cases, the lordosis, or hyperextension, frequently was more marked in the lumbar region than in the region of disease and more marked than was desirable, but the pressure rod on the knuckle obviated this, making the region of the gibbosity the centre of this arc (Figs. 5, 6 and 7).

The comparative value of suspension and hyperextension in the correction of the deformity of Pott's Disease is well shown in the photographs (Figs. 8 and 9). In Fig. 8 (a double photographic exposure) the lower photograph shows the child sitting on the kyphotone and the knuckle is well seen against the background. The upper photograph shows the child suspended by the Sayre head-sling and the knuckle is virtually of the same size it was before traction was made. In Fig. 9 we see traction has been made on the head, the arms have been carried upwards and backwards, the pelvis has been made fast and the pressure-rod has been applied, causing hyperextension at the knuckle, with the result that the spine is virtually straight.


' Hadra, Trans. Amer. Ortbo. Assoc, vol. iv, 20.5.

Cl)ipauU, Medicine Moderne, No. 20, Sixieme Ann^e. 9 Calot, Trans. Acad. M^d., Paris, 1896.

I" Goldtliwait, Trans. Amer. Ortlio. Assoc, vol. ir, 1S89.; Boston Med. and Surg. Jour., July 28, 1898.

"Eedard, Archivlo di Orthopedia, 1898, Fasc. 2.

'■Transactions, vol. xii, and N. Y. Med. Jour., May 12, 1900, 716.


This year I wish to present two recimibent kyphotones which carry out the same mechanical principles of hyperextension.

The larger is similar in many details to the one attached to the office stool, but differs in having the patient lie in a supine position on a plate or pelvic crutch instead of sitting up. The main bar slides in a solid metal block and thus can be lengthened or shortened to adapt itself to the patient's size.

The pressure-rod, attachments for hands and head-sling are similar to the upright kyphotone (Figs. 10 and 11).

The smaller kyphotone is quite simple, inexpensive and can be easily taken ajjart and carried in a satchel to a patient's house. It consists of two solid bases and uprights, one surmounted by a plate of sullicient size to support the pelvis and the second by a small plate to press upwards against the knuckle. This latter plate is adjustable and can be raised or lowered to increase the pressure and vice versa. The distance between the uprights can also be regulated by a rod attached to the bases by set-screws. The plate of the pressure-rod is incorporated in the plaster jacket during its application, but can be easily slipped out after the patient is removed from the machine by making an incision on one side of the pressure-rod in the plaster, which at this stage has not entirely hardened (McKim's modification). Then the opening thus made can be entirely and easily closed by moulding together the moist edges (Figs. 12 and 13).

Both of these recumbent kyphotones have been made to meet the need of acute or early cases or those with external pachymeningitis with paraplegic symptoms, in which it is detrimental to even sit up momentarily until the head-sling is adjusted and the superincumbent weight removed.

I have made an additional use of the larger recumbent kyphotone, and had attachments made for the mechanical correction of scoliosis of a severe and advanced grade, and I have used it also as a twisting correction machine daily on such cases or to obtain a corrected position in which it is deemed advisable to hold the patient constantly by means of a plaster jacket. Lovett has of late shown the value of hyperextension in the treatment of scoliosis," but the scope of this paper will not permit of further mention of this use of the recumbent kyphotone (Figs. 1-1, 15 and 16).

The question of which of these machines we shall use to prevent, correct or improve the deformity of Pott's Disease depends on the pathological condition we find the spine in, as shown by its flexibility, the size of the knuckle not necessarily being a determining factor of the latter.

(1) Earliest Stages. — At this period there is no deformity to correct, but the child will indicate by its posture, carriage or gait, grunting respiration, jjain, niglit cries, muscular spasm or some of the characteristic symptoms, that spinal trouble is present. The region can be located by an expert and prevention of deformity obtained by plaster jackets applied in slight hyperextension on the small recumbent kyphotone.


IS Boston Med. and Surff. Jour., June 14, 1900.


Febkuary, 1901.]


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At this stage caseation and conglomeration of the tubercles is beginning and traumatic contact from pressure of the healthy adjacent vertebra; is ripe to help break down the diseased vertebral body.

Unfortunately, the orthopedic surgeon rarely has an opportunity to try his skill at preventive medicine, as the general practitioner and general surgeon, for that matter, either retain the case themselves, using antiquated methods and recall hazily one lecture at college on " spinal disease," in which same "orthopedic lecture" nine times out of ten are given scoliosis, club-foot, flat-foot, bow-legs and all the rest, as well as " anteroposterior curvature." Or else the treatment (?) is referred to that paragon, the blacksmith — instrument-maker and pathologist.

(2) Beginning Deformity. — Thanks to the above treatment ( ?) or to the fact that the general practitioner et ah has been so busily engaged in diagnosticating the thoracic (ir abdominal pain he has failed to strip and roll the child over and look at its back, the knuckle is discovered by the child's mother. In such a case the vertebral body has partially broken down and abscess-formation has begun. Correction may be obtained by gravity with the small recumbent kyphotone and maintained by a plaster Jacket.

(3) More Advanced Cases. — In a case in which several vertebral bodies have broken down, and in wliich some adhesions or filirous ankylosis are ujst starting to form, either the large recumbent or upright kyphotone may be necessary to correct, with head-sling traction and pelvic fixation. It is at times astonishing to see a large hump disappear under this treatment (Figs. 8 and 9).

(4) Neglected or A/ihijlosed Cases. — If the ankylosis in a case is solid and condensing osteitis has taken place, no extreme force is justifiabU. Pain should be the guide to the amount of pressure or traction force used. Even, however, in large knuckles or 'humps, it may be found the ankylosis is not solid, and it is certainly justifiable to lessen the deformity of such a case by one of the more powerful kyphotones and allow the spine to heal in an improved position.

The method suggested by Bradford and Vose '* would seem also applicable to the first two of the foregoing varieties. This method consists of allowing the child to lie on its back and be slung in a position of hyperextension by a piece of firm cloth passing under the kyphos. This cloth, after passing around the side, is attached to a pulley, by means of which the hyperextension of the spine can be regulated.

When we consider the three regions of the spine to which hyperextension in Pott's Disease may be applied, we find difficulties confront us in each. In the cervical region with its normal lordosis the application of plaster of Paris bandages presents difficulties both as to efficiency, comfort and the avoidance of a bungling mass around the neck. A child's neck is so short, and with a traction head-sling on, it is next


"Annals of Surgery, 1899, vol. xvii, 323.


to impossible to apply an efficient bandage. The best plan is to use a steel back-brace with a head-support, but this will not correct the deformity. Instead of the head-support, or in conjunction with it, I have of late used a steel back-brace extending upward to or just above the kyphos and at this point had two buckles attached for a padded webbing strap to pass around the front of the throat. By tightening this strap the falling forward of the cervical segment can be limited or lessened, and it is astonishing how tight this strap can be borne. At first the patient gets quite livid in the face, but in a day or two the circulation adapts itself to the new condition and the child involuntarily holds the neck back, away from the strap, by means of the posterior muscles. I have seen no embarrassment of respiration and the superincumbent weight of the head is transferred to the healthy articular, transverse and spinous processes.

From the sixth (6) dorsal vertebra upward, our dependence must be ]ilaccd on the steel back-brace with supplementary straps to hold the shoulders and neck well backwards. From tliis point downwards the plaster jacket can be used, applied in hyperextension, but owing to the normal kyphosis, extreme hyperextension is difficult and entire correction of a severe deformity is rarely possible, except in very early cases. In the lumbar region, where normal lordosis already exists, it is easy to overdo the hyperextension with the result that the patient has a pot-bellied or sway-backed appearance. This can be avoided by making the head traction upward and slightly forward (not upward and backward) ; or, by a modification one of my assistants, Compton Eiely, has made, to exert pressure against the anterior superior spines in front and behind the trochanters major to prevent tilting forward of the pelvis, he having noticed in the majority of cases that the chief part of the lordosis was pelvic (Fig.' 17).

Another method of obviating this excess of lordosis is to flex the thighs on the body, thereby relaxing the psoas pull on the lumbar spine and preventing the rotation forward of the pelvis.

I have not attempted the use of anaesthesia with these methods of aiiplying correction to Pott's Disease, but rather avoided it as unnecessary and dangerous. The pain caused is inconsiderable in reduction and the resulting jacket is a relief to the painful symptoms previously present. These methods permit of the application of mechanically correct jackets, t. e.. those in which firm, even pressure is exerted against the three important points, the kyphos behind, the whole length of the sternum and ribs and the anterior spines of the ilia in front.

As I have said, in spines in which I suspect ankylosis I do not use great force, simply rendering them as straight as possible, short of pain. So-called " forcible correction," by which is meant manual traction and pressure under an ancesthetic, has but few adherents here in America, the majority of us feeling loath to tear by great force structures we could not appreciate on account of the anesthetic, pain


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being eliminated. Fatal and untoward results have been reported by Sherman," Jonnesco," Lorenz " and others.

The tracings (Fig. 18) show the results in a few cases of the Hospital for Criijpled Children. The stated duration of the disease is indicated under the initials of the case and it can be easily seen how much better results, as a rule, are obtained ultimately in cases treated early. On the other hand, when the size of the gibbosity is considered, quite an unexpected and appreciable improvement is shown in some of the eases.

As to the comparative value of the three machines, the upright kyphotone finds more general application than the


For conclusions as to these methods of correcting the deformity of Pott's Disease and applying plaster jackets, I would say:

First. The jackets thus applied fix the spine in the most advantageous position for lessening the tendency for the production of deformity.

Second. The rapidity and ease with which jackets may be applied.

Third. These methods are applicable to mid- and lowerdorsal and lumbar caries. Above the sixth (6) dorsal, a steel back-brace with head-support or throat-strap must be used.

Fourth. It seems comfortable to the patient, as the


S IE 1897 11"



Fig. 18. — Tracings from (12) out-patienfs treated hy kyphotones. Above each line is the date; to the left are the initials of the case and the duration when first seen. Between each pair of lines is given ihe vertebra chiefly involved


other two, as in the stage in which the majority of caset present themselves the knuckle is somewhat advanced in formation and slight adhesions exist; further, the patient can be viewed from all sides and the ultimate appearance of the jacket is at all times apparent. It is the quickest method, all things considered.

For the early stages the small kyphotone acts admirably, and for cases with paraplegia or acute sjTnptoms with an advanced kyphosis, the large recumbent khyphotone is needed.


•5 Pacific Record of Med. and Surg., October 1.5, 1898, 73. ■'Communication to Twelfth Internat. Congress of Med. " Deutsch med. Wochen., 1897, 556.


thorax is well supported and the superincumbent weight is removed from the diseased vertebral bodies to the healthy articular processes. Quite an appreciable gain has been noticed in the nutrition of patients after this method is used, due largely to the increased lung-expansion, which the posture renders possible.

Fifth. Absolute immobilization of the jjatient in the desired corrected position is obtained, one person being able to apply the methods without assistants to steady the patients, as nothing can slip at the most important moment.

Sixth. Hyperextension has been used constantly in the Hospital for Crippled Children in applying jackets on all suitable cases, from 1895 to the present time, and its efficacy has been demonstrated to our satisfaction clinically.


THE JOHNS HOPKINS HOSPITAL BULLETIN. FEBRUARY. 1901.


PLATE XI.



Tiihcrcuhir ioflciiiin;.


Fig. 1 SjiiiK'. Lower Dorsal Region. Child. Vertical anteroposterior section. One intervertebral disk destroyed and the anterior adjacent edges of vertebral bodies softened and disintegrated. Extension of the process backward to dura, and forward among prevertebral ligaments. Moderate knuckle. iNicholsi.





Fi(;. 2. — Diagram showing [\) Normal position of adjacent vertebrse.

(B) Falling forward of the vertebral bodies in caries of the spine.

(C) The aim of treatment of Pott's Disease by means of spinal extension in its true sense.

. — The planes of the vertebral bodies.

. — The line of the centre of gravity and of the superincumbent weiiibt.



Fig. .<{. The oritriuiil )'laster jacket stool. is;i,"i


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1901.


PLATE XII.






THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY. 1901


PLATE XIII.



Fig. 8. — A double pliotogfiiphic- cxposuri". Lower figure shows child (II. T. i iu sittinir |"isture.

Upper tiijurc shows rhihl ill. T.I snspciuh-d liy lu';ul, with no ri-diu'tioii in the kypliosis.


Fir., il. —Shows cliild (II. T. ) hyperc-xteiuhHl with obliterutiou of the kyphosis.



Fio. 10. — Case (\V. W.) showiim- di'forinit\ . Kyphotoue sci'U on the ri^■ht.


Kic. 11. — Case iW. W.) sreu lOi the hirue ri'cuinhent kyphotone.



Fic. \2. — Case (B. H.) and small reninibcnt kyidiotun.-.


Fig. 13. — Case (B. H.) showint;- complete (dditcration of the deformity.


THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1901.


PLATE XiV.




Fig. 14 — Case (C. N.) scolioti


Fid. ifi. —Case (C. N.) sliowiiiy' correction effected on large recnmbent kyphotone anil maintained by a plaster jacket.


Fiii. 17 — Conipton Riely's moditication, adjustable by set-screws to any pelvis. Arrows indieate imints where pressure is made.



Ki


o. I.-,._Case (C. N.) on large recumbent kyi>liotone.


February, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


37


Seventh. Aside from the danger of excessive and unequal force being used manually by several persons making traction for " forcible correction " under an anaesthetic, these methods enable one operator to adjust to a nicety his pressure and traction without an anesthetic and further enable him to make his diagnosis as to the pathological stage the process has reached, which the size of the deformity does not always tell, in regard to the degree of ankylosis.

EeCENT BlIiLIOGRAPHY ON PoTT's DISEASE.

Anders: Arch. f. Chir., 1898, Ivi, 703.

Aue: Ann. Euss. Chir., St. Petersburg, 1898, H. 3, 472.

Babaeei: Eaceoglitore med. Forli.. 1897, xxiv, 25.

Barragony y Bonet: Eev. de ther. med. chir., 1899, 3-12.

Banning: Interstate Med. Joiir., St. Louis, June, 1900.

Bilhaut: Ann. de chir. et d'orth., Paris, 1898, xi, 4, 140; Med. enfant., Paris, 1897, 318; Ann. de chir., et d'orth., Paris, 1897, 193; Proces verb, Congr. de chir. franc, 1897, xi, 327.

Blondez: Ann. de la Soc. Beige de chir., Brussels, 1898, vi, 72.

Bobrofl: Med. obozy., Moscow, 1897, 696.

Bouquet: Eev. d'orthop., Paris, 1900, xi, 217-218.

Bradford and Vose: Annals of Surgery, 1899, xvii, 223.

Bradford: Med. Press and Circ, Lond., n. s., Ixix, 13G137; Eev. mens. mal. I'euf., Paris, 1900, xviii, 450-455.

Bradford and Cotton : Bost., M. and S. J., 1900, cxliii, 12, 277-283.

Braun: XXVII Congr. deutsch. Chir., 1898.

Broca: Presse med., 1897, 213.

Brun: Ibid.

Buell: Pacific Coast J. Homoeop., San Fran., 1899, vii, 1-11, 4 pi.

Calot: Arch. prov. de chir., 1897, vi, 557; Eev. de ther. med. chir., 1897, Ixiv, 573; Transactions of the Clinical Society of London, 1897-98, xxxi, 26; Eev. de chir., Paris, 1897, xviT, 1019; Proces verb., Congr. de chir. franc, 1897, xi, 299; Wien. med. Presse, 1897, No. 35.

Capelli: Tribuna Med., Milan, 1898, xii, 152.

Carleton: Yale Med. Jour., New Haven, 1900, vi, 315322.

Chipault: Presse med., Paris, 1897, 240; Eev. de chir., Paris, 1897, xvii, 1026; Assoc franc de chir., Paris, 1897, xi, p. 352 (Proces verb.); Transactions of the Clinical Society of London, 1897-98, xxxi, 43; Du mal de Pott, Paris, 1897; Gaz. des hop., 1897, xxi, 197; Ibid., 1897, Ixx, 900.

Clarke : British Medical Journal, London, 1898, i, 429.

Czajkowski: Gaz. Kek. Warszawa, 1898, xviii, 64.

D'Addosio: Puglia Med., Bari, 1898, vi, 116.

Delcroix: Presse med. Beige, Brussels, 1897, xlix.

Dane: Pediatrics, K Y., 1900, x, 14-17.

De Eothschild: Proges med., Paris, 1898, viii, 497.

Ditman: Euss. Arch. Pathol. Klin., St. Petersburg, 1898, V, 207.

Drehmann: XXVII Congr. deutsch. Chir., 1898.


DiTcroquet: Deutsch. med. Woch., xxv, 556; These de Paris, 1898; Twelfth International Congress at Moscow.

Freeman: Annals of Surgery, 1898, xxvii, 463.

Freiberg: Transactions of the Academy of Medicine, Cincinnati, 1897-98, 213; Cincinnati Lancet Clinic, 1898, xi, 151.

Galloway: Canada Journal of Medicine and Surgery, 1899, v. 77.

Gayet : La Gibbosite dans le mal de Pott, Paris, 1897.

Gevaert: Ann. de la Soc. Beige do chir., Brussels, 1898, vi, 115.

Gibney: Medical News, New York, 1898, lxxiii,_ 391; Transactions of the American Orthopedic Association, 1898, xi, 83; New York Medical Journal, 1898, Ixvii, 427.

Golthwait: Transactions of the American Orthopedic Association, 1898, xi, 897.

Guibal: Bull, et mem. Soc. Anat. de Paris, 1899, Ixxiv. 945-956.

Greenwell: Fort Wayne Med. J.-Mag., 1899, 413-416.

Guyot and Oilier: La Gibbosite du mal de Pott, Paris, 1897.

Hallstrom: Duodecjmus; Haelsink, 1897, xiii, 344.

Haudek : Wien. med. Woch., 1899, xlix, 1930.

Helferich: Zcitschr. f. orth. chir., 1897, v, 342; Zeitschr. f. prakt. Aerzte, 1897, No. 16, 541.

Heusner: Deutsch. med. Woch., 1897, xxiii, 773.

Huhn: Arch. f. Klin, chir., Ivi, 1898, 697.

Iloffa: Miinch. med. Woch., 1898, xlv, 545; Deutsch. med. Woch., 1898, Nos. 1 and 3; Arch. f. klin. Chir., Ivii, H. 3.

Hoffa: Miinchen, 1900, 28 pp., 10 figs., Seitz u. Schauer.

Hoffmann: Pediatrics, N. Y., 1900, x, 50.

Jeannel: Arch. prov. de chir., 1897, vi, 383.

Joachimsthal : 70 Naturf. u. Aerzteversamml., Diisseldorf, 1898.

Jones: Liverpool Medico-Chirurgieal Journal, 1898, xviii, 154; British Medical Journal, 1897, ii, 336.

Jonnesco: Spitalul. Bucarsci, 1897, xvii, 244; Annals of Surgery, Philadelphia, 1897, 789; Arch, de sc med. de Bucharest, Paris, 1898, iii, 1; Eev. Mens, de Med., Madrid,

1898, iii, 147; XII Internat. Congr. Chir.

Jonnesco and Melun: Eevista de chir., 1897, No. 5.

Joseph, J.: Deut. Med. Woch., Leipz. u. Berl., 1900, xxvi, Ver.-Beil., 171-172.

Kirmisson: Bull, et mem. Soc. de Chir. de Paris, 1900, xxvi, 291-292.

Konig: XXVI Congr. deutsch. Chir., 1898.

Krause : Ibid.

Kummell : Ibid.

Lacroix: F. Arsenal med.-chir. contemp., Paris, 1900, vii, 21-28 and vii, 41-46, 6 tigs.

Lange: Centrbl. f. Chir., 1898, No. 12; Wien. Klinik,

1899, xxv, H. 1.

Levassort: Eev. de chir., 1897, xvii, 1024; Proces. verb., asso. franc de chir., 1897, xi, 349; Eep. de therap., Paris, 1898, XV, 447.

Ligorio: E. Eiv. di Chir., Torino, 1899, 1, 65-69.


38


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 119.


Lorenz: Deutsch. med. Woch., 1897, 556; Zeitschr. f. orth. chir., 1897, v, 343; Twelfth luteruational Congress at Moscow.

Lorett: Boston Medical and Surgical Journal, exxxviii, p. 328.

Malherbe: Gaz. med. de Nantes, 1896-97, xv, 132; Ann. de chir. et d'orth, 1897, 218.

Martin: Miin. Med. Woch., 1899, xlvi, 1444.

Menard: Gaz. med. de Paris, 1897, i, 231; Eev. de chir., Paris, 1897, xvii, 526; Presse med., 1897, 13; Bull, et mem. Soc. de chir. de Paiix, 1897, xxiii, 363; Eev. d'orth., 1899, 173, 301, 379. Ibid., 1900, xi, 123-146.

Menard and Guibal: Rev. d'orth., 1900, No. 1, 35; Bull, med., Paris, 1899, xiii, 856.

McCurdy: Penn. M. J., Pittsburg, 1899, iii, 62-69.

Meneiere: Med. mod., Paris, 1899, x, 313-316.

Meyer: Zeitschr. f. orth. Chir., 1898, vi, 201.

Miilot: These de Paris, 1898.

Monod: Bull, et mem. Acad, de med., Paris, 1897, xxxvii, 695; Gaz. des hop., Paris, 1897, Ixx, 656; Presse m6d., 1897, No. 57.

Murray: British Medical Journal, 1897, ii, 1630; American Journal of the Medical Sciences, May, 1898.

Myers: Am. Pract. and News, Louisville, 1900, xxix, 227-228; Med. Times and Reg., Phila., 1900, xxxviii, 118-119.

Nasse: Berlin, klin. Woch., 1898, xxxv, 13.

Nebel: Samml. klin. Vortriige, Leipzig, 1897, No. 191.

Pean: Twelfth International Congress at Moscow.

Peckham: Transactions of the American Orthopedic Association, 1898, xi, 109; Archives of Pediatrics, 1898, :fv, 641.

Phelps: Post-Graduate, 1899, xiv, 702; Med. Register, Richmond, Va., 1899, ii, 397-420; Trans. Med. Soc. St., N. Y., 1899, 209-235.

Phocas: Asso. franc, de chir., 1897, xi, 322; Med. moderne, 1898, No. 52; Rev. de chir., 1897, xvii, 1021.

Redan et Loran: Am. X-Ray J., St. Louis, 1899, iv, 540541.

Redard: Rev. de chir., Paris, 1897, xvii, 1021; Ass. franc, de chir., 1897, xi, 312; British Medical Journal, 1897, ii, 1642; Twelfth International Congress at Moscow.

Ridlon: Chicago Medical Recorder, 1898, xiv, 134; Medical News, New York, 1898, Ixxiii, 484; Transactions of the American Orthopedic Association, 1898, xi, 120; Journal of the American Medical Association, 1898, xxxi, 71.


Salayer and Sousa: Med. Contemp., Lisbon, 1897, xv, 237.

Schanz: Deutsch. med. Woch., 1898, 387; Zeit. f. Ortho. Chir., Stuttg., 1900, vii, 531-533.

Schatalow: Med. Obos., 1899, Ii, lift. 5; Abstr. Med. der Gegenw., Berl., 1899, 11, 443.

Schede: Zeitschr. f. prakt. Aerzte, 1898, vii, 485; Arch. f. klin. Chir., 1898, Ivii, 507; Twelfth International Congress at Moscow.

Sherman and Brunn: Pacific Medical and Surgical Recorder, 1898-99, xiii, 73.

Subotin: Rev. illustr. polytech. med. et chir., Paris, 1899, xii, 90-92; Centrbl. f. Chir., 1898, 460.

Smith: Lancet, London, 1898, ii, 497.

Tilanus: Tijdschr. v. Geneesk., Amsterdam, 1898, xxxiv.

Toles: Southern California Practitioner, 1898, xiii, 401; Ibid., August, 1899.

Townsend : Lancet, Lond., 1900, 1, 232-233, 1 fig.

Trendelenburg: Abstr. Ann. Surg., Phila., 1900, xxxi, 667-668.

Tubby: British Medical Journal, 1897, ii, 1501; Practitioner, 1898, Ix, 28.

Tubby and Jones : Transactions of the Clinical Society of London, 1897-98, xxxi, 15.

Twitchell: J. Med. and Sc, Portland, 1900, vi, 41-49.

Verger et Lanbie: Progres med., Paris, 1900, 3, 5, xi, 49-53.

Villemin : Ann. de med. et chir. inf., Paris, 1900, Iv, 253260.

Vincent: Lyon Med., 1897, Ixxxv, 333; Ann. dc chir. et d'orth., 1897, xxiv, 207.

Vulpius: Centrbl. f. Chir., 1897, xxiv, 1257; Deutsch. med. Woch., 1898, xxiv, 379; Arch. f. klin. Chir., 1898, Mi; Twelfth International Congress at Moscow; Centralbl. f. de Grenzgeb., etc., 1899, ii, 673.

Wirt : Bull. Cleveland Gen. Hosp., 1899, 1, 30-39.

Wiart: Rev. de chir., Paris, 1898, xviii, 777; Ibid., 1899, xx.x, 33, 170.

Wider: Fork. Svens. Luk. Sallsk. Sammoek., Stockholm, 1898, 3.

Williams: Lancet, London, 1898, i, 1352.

Wolff: Berlin, klin. Woch., 1898, Nos. 7, 8.

WiiUstien: Arch. f. klin. Chir., 1898, Ivii, 485; Centrbl. f. Chir., 1898, xxv, 705.

Young: Internat. Med. Mag., Sept., 1900.

Zenatski: Wratsch., St. Petersburg, 1897, xviii, 877.


TWO EXAMPLES OF BENCE JONES' ALBUMOSURIA ASSOCIATED WITH MULTIPLE MYELOMA.^

A PRELIMINARY REPORT.

By Louis P. Hambuegek, M. D., Assistant in Medicine, Johns RopHns University.

albuminous body having peculiar properties. It had been voided by one of his patients in large quantity — about 3,500 cc. — in the twenty-four hours. We examined it and found that it afforded the reactions which I shall demonstrate to vou to-ni<;ht.


On the 13th of last month. Dr. Iglehart brought me a specimen of urine with the remark that it contained an


' Deitnnstratiiin before the Johns Hopkins Hospital Medical Society, November 5, I'.IOO.


February, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


39


As you see, it is very pale, of an acid reaction, with a specific gravity of 1,004. It gives a white ring when floated over nitric acid. Heated to a temperature of about 55^, a heavy milk-white precipitate appears. Boiled, the fluid becomes clearer, only to become more turbid on cooling. The addition of acetic acid to the fluid after reaching its maximum turbidity causes it to become clear again. A few drops of nitric acid yield a precipitate which dissolves completely on boiling and reappears on cooling. In the Esbach albuminometer the proteid content reaches 0.27 per cent. The urine gives a strong biuret reaction. Let it be added that no easts were seen even in a centrifugalized specimen.

We recognized that this condition was no ordinary albuminuria. It is not the usual urine of nephritis, although the positive Heller's test alone might lead one astray. But the usual albumins of albuminuria, after being precipitated by heat, are not dissolved by the addition of a small quantity of acetic acid; they do not tend to redissolve on boiling; the nitric acid precipitate does not dissolve on boiling and reappear on cooling and the biuret reaction is wanting. The substances which do offer these reactions are the albumoses, the condition is that of albumosuria, and so I designate it in the present instance.

From an acquaintance with the literature on the subject, I was able to point out to Dr. Iglehart that this condition of so-called albumosuria in such a marked degree was an accompaniment of sarcomatosis of the bone, and, indeed, of a peculiar variety originating in the marrow and known as myelomata, new growths affecting for the most part the skeleton of the trunk — the vertebrae, the clavicles, the sternum and the ribs. Whereupon he recalled that his patient had had on two occasions most intense pain in the ribs and had lost much weight during the past three months.

So convinced was he by the data which were presented to him, that he gave a member of the family the serious prognosis which the condition merits.

Dr. Iglehart has given me further details of this peculiar illness. He was called to see the patient, a lady 49 years of age, in August, 1900. Previously healthy, she was suddenly seized at this time with sharp pain over the 9tli left rib near its cartilaginous attachment. The pain was severe and increased on deep inspiration. There was tenderness on pressure over the painful point. Neither crepitus nor a friction rub was present. The condition so resembled a fracture that he considered the patient had injured the rib, but he could elicit no history of trauma. Within three weeks the pain had disappeared. She was again seen in September, this time complaining of nausea without apparent cause. Her general health had suffered; she had lost thirteen pounds in weight.

Early in October she was seized a second time with pain, now in the region of the 8th right rib in the mid-axillary line. It was at this time that the remarkable urinary condition was discovered. The patient herself had noted that since the past summer she had drunk more water than usual and had voided a larger quantity of urine.


Dr. Osier saw the patient on November 3d, two days ago, and aside from a slight pallor of the visible mucous membranes, the physical examination was negative.

In short, however absurd it may seem at first thought, from examinations of the urine I was confident I had established the probable diagnosis of new growth of the bonemarrow.

Excepting in diseases of the urinary tract itself, I know of only one other instance in which, without having seen the patient, the diseased organ may with great probability be determined from an examination of the urine. I refer to the presence of leucin and tyrosin in the urine as a sign of widespread destruction of liver siibstance.

Following the recognition of this example of albumosuria with its consequent diagnosis, Dr. Osier called my attention to the patient who lies before you, and it is to his courtesy that I am indebted for the privilege of reporting an abstract of her history.

The patient is a colored woman 50 years of age, who entered the medical clinic of the Johns Hopkins Hospital October 10, 1900, complaining of "rheumatism" and a " sprained hip." Kegarding her family history she can only recall definitely that her father died of old age; that her mother, eight brothers and a sister have died from causes unknown to her; and that a sister is living and well.

She suffered the diseases of childhood and twenty-four years ago had " rheumatism " in both knees. Ten years ago she contracted grippe, and since then has had a cough each winter.

For about a year she has had pain in the region of the right groin and hip. One night last June, while picking up a bucket of coal, she experienced a remarkable sense of lengthening in the left arm and the next morning found that she could not raise it to her head because of pain and a feeling of weight. A week later the right arm became affected. She had pain here as well as in the shoulder, back of neck and chest. About this time the patient noticed a swelling the size of a hen's egg on the back of her head. Pain and stiffness in the arms continued so that by August she could neither cut her food nor feed herself. Six days before admission to the hospital, while walking, the right leg " gave away " without apparent cause. She fell to the ground, and since then has not been able to stand or walk. She has suffered great pain in the right hip. The patient has lost much weight and strength during her illness.

As you see, she is markedly emaciated. The mucous membranes are pale. Any movement of the body calls forth great pain. Over the occipital region there is a round, soft, fluctuating mass about 10 cm. in diameter, not adherent to the skin, not movable on the deeper tissues, not tender. A nodule three to four cm. in diameter is visible on either clavicle over its inner third. The one on the left is a little larger and more definitely circumscribed. It has evidently eroded the bone, for manipulation causes pain and crepitus. There is another tumor in the left supraspinous region about 4 cm. in diameter and evidentlv connected with the


10


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[No. 119.


acromion process of the scapula. The right lower limb is rotated outward and is abducted. The upper third ol the thigh on this side is markedly enlarged and deformed by the presence of a tumor, about the size of a child's head, projecting from its postero-external aspect. It is firm and tender on pressure. An attempt to move the limb causes intense pain.

The lungs are clear on percussion. Here and there an occasional crackling rale is heard with inspiration. The poiut of the heart's maximum impulse is visible in the fourth left interspace 7 cm. from the niidsternal liue. A systolic murmur is audible at both the mitral and pulmonary areas. The abdomen is distended and held rigidly. No masses are to be felt. Neither the edge of the liver nor the spleen is palpable. There is no general glandular enlargement. The red blood-corpuscles number 3,51:8,000; the leucocytes, 4,500; haemoglobin, 52 per cent. The relation of the diferent varieties of white corpuscles is practically normal.

Now, here is a case in which the clinical picture is clearly one of sarcomatosis of the bone. Does the urine exhibit the characteristics of albumosuria ? As a matter of fact it docs.

The urine is turbid, light yellow, and GUO to 800 cc. are voided daily. It is usually alkahne, though at times neutral iu reaction. Its specific gravity varies from 1,013 to 1,030. Heller's reaction is positive. Acidified and heated to a temperature of 56° C, a heavy white precipitate appears. It redissolves in part on boiling and returns on cooling. The nitric acid precipitate disappears on boiling to reappear on cooling. The mis:ture assumes a darker color and particles of the precipitate adhering to the tube become pink. The biuret reaction is marked. The proteid content measured by the Esbach albuminometer varies from 0.3 to 0.6 per cent. Finally, Dr. Dorothy Reed has, by saturating the m-ine with ammonium sulphate and redissolving the precipitate, demonstrated more precisely the albuminose nature of this urinary constituent.

Some hyaline casts are present in the sedmient.

This second case needs no peculiar explanation, but our diagnosis of neoplasm of the bone from examinations of the urine of Dr. Iglehart's patient needs justification.

The occurrence ia the urine of proteids other than serum albumin is an old observation. Almost thirty-five years ago Lehmann ' made the statement that every albuminous urine contained in addition to serum albumin, serum globulin; in small quantity to be sure, but demonstrable. A little while later Gerhardt,' in an endeavor to distinguish between renal and febrile albuminuria, discovered in the urine a proteid substance which was not coagulated by boiling. It was present in small quantities in a variety of ailments, especially in those accompanied by high temperatures — diphtheria, typhoid and typhus fevers. Gerhardt designated the condition " latent albuminuria." Subsequent researches confirmed and extended these observations and established the close relation between the " latent albumin " of Gerhardt


sVlrch. Arch., 1866, Bd. xxsvi, 8. 125. 3Deut. Arch. f. Kl. Med., 1869, Bd. v. S. 215.


and peptone, the product of gastric digestion of albuminous substances. Peptonuria of slight degree was found to be an accompaniment of very many disorders: nephritis, suppurative processes, acute yellow atrophy of the liver, ulcerative diseases of the intestine, including typhoid fever and carcinoma of the bowel; it was described as occurring in scurvy. In short, so manifold were the conditions under which small quantities of peptones were found iu the urine that conclusions of much practical value could not be drawn.'

With the well-known researches of Kiihne and Chittenden on gastric digestion, the subject-of peptonuria entered a new phase. You will recall that they established the existence of a number of products intermediate between albumin properly speaking and peptones, namely, the albumoses. Differing among themselves in some details of solubility, they give certain of the reactions of the albumins and like them are precipitated by ammonium sulphate. Yet they partake of the nature of peptones, for they are not precipitated by boiling and they give the biuret reaction. In the light of Kiihne and Chittenden's work, the conclusions concerning peptonuria had to be revised; probably all instances of "peptonuria " in the old sense are, as a matter of fact, examples of albumosuria. Using special methods for their recognition, albumoses have been found iu small quantities in the urine of individuals suffering from various acute ailments; most constantly, perhaps, in pneumonia, purulent meningitis and .empyema.

Now, this acute, transitory or slight albumosuria cannot be confused with the condition demonstrated to-night. In this second class the presence of a comparatively large amount of an albmuose-like substance so alters the behavior of the urine toward the usual reagents that, as you have seen, the condition can be recognized without the employment of a relatively elaborate method. Moreover, in addition to the comparatively excessive degree, the albumosuria is persistent over long j^eriods of time, not transitory.

The first recorded observation in this class was reported by Henry Bence Jones before the Eoyal Society of London in 18-47.° He begins his communication thus : " On the first of November, 1845, I received from Dr. 'Watson the following note, with a test-tube, containing a thick, yellow semisolid substance: The tube contains a urine of a very high specific gravity; when boiled it becomes highly opake, on the addition of nitric acid it effervesces, assumes a reddish hue, becomes quite clear, but, as it cools, assumes a consistence and appearance which you see: heat reliquefies it. What is it ? " Bence Jones then proceeds to tell of his researches. The urine was voided by a grocer 45 years of age who had been " out of health " for thirteen months. The urine showed variations in its coagulability; as a rule it bore brisk and prolonged boiling without coagulating. With


See Senator, Ueber Peptonurie, Deut. lied. Wochenscbr., 1S95, Bd. 21, S. 317.

sZeitschr. f. Biol., 1S83, Bd. xix, S. 1.59, 209; 1884, Bd. xx, S. 11. «Pbil. Trans. Royal Soc, 1848, Pt. 1, p. 55.


Febkuakt, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


41


copper sulphate and caustic potash, it gave a claret color. Most characteristic of all, Bence Jones thought, was its behavior toward nitric acid. This reagent gave a precipitate which dissolved on heating and reappeared on cooling. On January 3, 181G, he makes the note that the patient died, adding, " The following day 1 saw that the bony structure of the ribs was cut with the greatest ease and the bodies of the vertebrae were capable of being sliced off with a knife." . . . " The kidneys were sound both to the eye and microscope."

In 1850 Dr. Macintyre, who had attended the patient, published some details of his illness.' The man dated his ailment from a violent strain he had sustained in September, 1844, in vaulting out of an underground cavern. On coming to the ground he felt as if something " gave away " within his chest, with the further result that he suffered at the time agonizing pain. The pain gradually subsided, but about a month later he was again seized with sharp pain in the chest, this time without an apparent cause. In the following spring he had another severe paroxysm, the pain was referred to the right side between the ribs and the hip and was considered j)leuritic in origin. These periods of intense suffering alternated with periods of marked amelioration. In time, however, every movement of the trunk was attended with excessive pain. The poor sufferer became ansemic and lost much weight and strength. Diarrhoea supervened, and finally, after a sixteen months' illness, the patient died exhausted. Physical examination failed to reveal the nature of this painful and fatal illness. The remarkable urinary reactions were noted two days before the specimen was sent to Bence Jones. Post mortem the condition was designated " Osteomalacia fragilis rubra." The substance of the sternum, ribs and vertebras was rarefied and crumbling; their interior filled with a soft red gelatinous matter which microscopically consisted of " granular matter, oil globules, nucleated cells, constituting the bulk of the mass — a few caudate cells and blood-disks extravasated largely amongst the other cells, and giving the red color to the gelatiniform mass."

Bence Jones' observation was almost forgotten, when in 1883 Kiihne ° published the result of an examination of urine sent to him in 1869 with a clinical history by Stokvis, a Dutch clinician. In the specimen he rediscovered the reactions of Bence Jones and showed their close relation to those of his own digestive albumoses. The patient died after a nine months' illness which had been diagnosed as osteomalacia, but an autopsy was not held.

Several years elapsed and a third case was described from the clinical standpoint by Kahler and chemically by Huppert.° A physician was the patient, the clinical diagnosis was osteomalacia; the urine afforded Bence Jones' reactions but post mortem instead of osteomalacia, a multiple roundcell sarcoma of the bone-marrow; in other words, a mul


tiple myeloma was disclosed. Thereupon Kahler suggested that the presence of Bence Jones' reactions might be of service in the diagnosis of multiple myeloma. Might not the other two cases of so-called osteomalacia with albumosuria have been instances of this disease ? Bence Jones had recognized that the association of the unusual urinary reactions and the disease of the bone was probably not a fortuitous one, for at the conclusion of his communication he writes : " This substance must again be looked for in acute cases of mollifies ossium." But it is Kahler who first identified the pathological condition in these cases of bone disease and albumosuria with the affection previously described by V. Eustizky '" and called by him " Multiples Myelom." The Italians give Kahler due credit, for Bozzolo's ease is presented under the caption " Sulla malattia di Kahler." " By the accumulation of recorded eases, Kahler's surmise has become a fact.

To be brief, let me say that in the fifty years following Bence Jones' presentation of his case before the Royal Society, there were published and available for criticism only four observations on albumosuria associated with primary bone disease. Within the last three years, however, eight additional cases have been recorded. In eight of the thirteen cases the autopsy has disclosed neoplasms which must be classified as myelomata. In two cases the tumors were visible, in the remainder there was no record of a post-mortem inspection.'"

In this series are not included two examples of Bence Jones' albumosuria which seem to be exceptions to the general rule, since in one there was no ground (albumosuria excepted) for assuming a disease of the bone, while in the other there were, to be sure, changes in the bone-marrow, but tlieir identity with those found in myeloma could not be satisfactorily established.

The first case is described by Dr. Fitz " as one of myxcedema in which marked and persistent albumosuria was a feature. The patient died while under thyroid therapy. Inasmuch as no autopsy was held, the case is not above criticism. It is in the course of this publication that brief reference is made to the only recorded American observation on multiple myeloma and albumosuria.

Askanazy's case of lymphatic leukemia " constitutes the second apparent exception.

His patient was a man fifty-one years of age, who was ad


'Med. Chlr. Trans., London, 18.50, vol. 3.3, p. 211.

Loc. cit. sPrag. Med. Woclienschr., 1889, Bd. 14, 8. 33.


'«Deut. Zeitschr. f. Chir., 1873, Bd. 3, S. 163.

" VIII Congresso dl medicina interna, 1897, (Transactions).

'■'Tiie cases reported are tbose of Bence Jones, loc. cit.; Kiihne and Stokvis, loc. cit.; Kahler, loc. cit.; Stokvis, quoted by Rosin ; Seegelken, Deut. Arch. f. Kl. Med., 1897, Bd. 58, S. 126; Rosin, Bcrl. Kl. Wochenschr., 1897, Bd. 34, S. 1044; Bozzolo, loc. cit.; Ewald, Wien. Kl. Wochenschr., 1897, S. 169; Bradsl\aw, Med. Chir. Trans., London, 1899, p. 2.51; Fitz, Amcr. Jour, Med. Sc, 1898, vol. 116, p. 30; Naunyn, Deut. Med. Wochenschr., 1898, Vereins Beilage, S. 217; Ellinger, Deut. Arch. f. Kl. Med., 1899, Bd. 62, S. 25.5; Sternberg, Nothnagel's Spec. Path. u. Ther., 1899, Bd. vii, Tb. ii, Abth. ii, S. .57.

"Loc. cit.

"Deut. Arch. f. Kl. Med., 1900, Bd. 68, S. 34.


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[No. 119.


mitted to the hospital iu June, 1898. In the summer of 1897 he began to complain of feeling weak; he lost weight and was easily fatigued. Six months later he noted that the cervical glands were enlarging. On admission he was somewhat anfemic; the legs and the abdominal wall were cedematous. There was a moderate enlargement of the lymph glands of the neck and axilte; several small subcutaneous glands were palpable over the chest wall. A glandular tumor about the size of a man's head occupied the right upper quadrant of the abdomen. Small tumors were felt in Douglas's fossa. The blood showed the changes of lymphatic leukaemia. The urine exhibited Bence Jones" albumosuria. Five weeks later the patient died, and acute pulmonary cedema being the immediate cause of death. At the autopsy the ribs wei-e found very thin; four of them were fractured presumably in transporting the cadaver. A thick, gelatinous marrow, the color of meat, occupied the wide meshes of the bony structure. Microscopically, this marrow was composed of colorless elements, among which the lymphoid cells predominated. There was a hyperplasia of all the lymphatic glands.

Unless the process is to be viewed as a diffuse myeloma, here is an exception. Until the relations of the myelomata to leukaemic and pseudo-leuksemic processes are determined, Askauazy's case must be considered one of lymphatic leukaemia associated with Bence Jones' albumosuria. But this single possible exception need not vitiate the importance of albumosuria as a sign of boue-niarrow tumors, seeing that in all other instances where the investigation has been thorough, a multiple myeloma has been the underlying condition.

To demonstrate the converse proposition that aU cases of multiple myeloma are accompanied by Bence Jones' albumosuria is not possible, the data being insufiQcient. Several considerations must be taken into account. The first is the difficulty in deciding just what a myeloma is; a difficulty to which I shall again refer. These urinary reactions seem to be specific for myeloma, not an accompaniment of every bone tumor. At the last German Congress for Internal Medicine A'aunyn " stated that he had observed a patient whose skeleton was riddled with metastatic carcinomatous growths but the urine failed to give the reactions of Bence Jones.

Furthermore, it must be borne in mind that the time of the appearance of the reactions in the course of the disease has not been definitely determined. In the Stokvis-Kiihne ease the albumosuria appeared not until the illness was well advanced and disappeared three months before death. But this observation is exceptional ; the albumosuria is, as a rule, an early sign and is persistent.

Quantitatively it is subject to great variations. In Ellinger's case the proteid content averaged from ^ to i per cent, while in the famous specimen submitted to Bence Jones, it reached the high percentage of six and nine-tenths. Even in the course of any single ease there may be marked

" Verhand. d. Cong. f. inn. Med., 1900, S. 40R, et. spq.


remissions in the intensity of the reaction, a fact noted by Matthes and likewise observed in the second case of our series.

It must be shown, then, that the diagnosis of the nature of the bone tumor has been well founded and that repeated urinary examinations have been made before one can accept V. Jaksch's statement that he has observed cases of multiple myeloma in which there was not a trace of albumose in the urine."

The exact nature of the substance giving rise to the reactions of Bence Jones has not been determined. All investigators have noted the close relation existing between these reactions and tliose of the albunioses in Kiihne's sense, and yet when isolated it differs in minor features from any of the known digestive proteoses. Eecently before the German Congress just referred to, Magnus-Levy "' denied its albumose character. He stated that he had isolated Bence Jones' proteid in crystalline form; that its property of being dissolved at the boiling-point was not constant; that by the addition of small quantities of salts or extractives such as urea or by slight alterations in the physical conditions its solubility or insolubility at a temperature of 100 degrees could be brought about at will. Moreover, he argued, its structure must be more complex than the albumoses, for as a result of its peptic digestion almost all of the primary split products, namely, the albumoses, were obtained.

The origin of the proteid is as obscure as its character. Ellinger's attempt to extract it from the marrow tumors was not successful. But his demonstration of its presence in the blood is fairly satisfactory. On the other hand, in his case of hmiphatic leukapmia Askanazy could not demonstrate the reactions in the blood, yet was successful in finding the proteid in an extract of the bone-marrow. You will see that these are obscure problems requiring further research.

Aside from the reactions to which I have so often referred, there are no constant alterations in the urine. Kahler"s patient voided 2,230 cc. in 24 hours, but he was accustomed to drink large quantities of alkaline water. Other^\'ise there is no reference to a polyuria comparable to that exhibited by Dr. Igleharfs patient.

Bradshaw's patient voided a milky urine from time to time for a jenT previous to the onset of any localizing symptoms.

Besides the peculiar albuminose proteid the urine usually contains albumin in traces. In Senator's case " there was a coexisting nephritis manifesting itself by the presence in the urine of numerous casts and albumin. At the autopsy the kidneys were large and had suffered fatty and amj'loid degenerations. Needless to add that a myeloma was also disclosed.

I pass now to a more accurate description of the nature of myelomata. Multiple new growths of the bone-marrow, they do not correspond to the tisual conception of malignant


'5 Loc. eit.

IS See Rosin, loc. cit.


" Loc. cit.


" Loc. cit.


February, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


43


neoplasms in the Cohnheim sense, inasmuch as they probably never metastasize.

The name " multiple myeloma " originated with v. Eustizky,'" who viewed the process as a simple hypertrophy of the bone-marrow, and for these reasons : the tumors were present only in the bones and, indeed, originated only in the bone-marrow, that although multiple, they did not metastasize; therefore, did not belong to the class of malignant neoplasms. Since v. Rustizky's publication there have been several attempts to gather together the scattered records of apparently similar growths.'" Thus there have been collected examples of diseases of the bone with most diverse titles— osteomalacia, medullary pseudo-leuktemia, sarcomatous osteitis, malignant osteomyelitis, lymphosarcoma. Histologically in the majority of instances the structure has been that of a round-cell sarcoma. Eecently, Wright has described a myeloma in detail in connection witli Fitz's case. The tumor elements, according to his research, really form a variety of plasma cells. A myeloma does not originate in the marrow cells as a whole, but in only one of its elements, the plasma cell. Following the results of this important contribution, the tumor may be classed as a plasmoma.

In gross, these tumors form masses of soft reddish tissue of various sizes, often ill-defined, replacing the normal marrow and osseous substance. The sternum, ribs, vertebra? and skull are prone to the affection though all the bone may be involved. The tumors may or may not appear on the exterior. The bones are softened and apt to suffer pathological fractures with resulting deformities. These facts of pathological anatomy explain in part the varying clinical pictures of multiple myeloma.

A disease of later life, it affects males more frequently and runs its course as a rule within two years. Bozzolo's patient lived four years after the onset of the iirst symptoms, while the physician under Kahler's care suffered eight years before death relieved him. The recital of this history makes a harrowing tale, but as it serves to illustrate one type of the disease I shall present it in some detail:

Dr. Loos was in 1879 a well-developed man, 46 years of age, of healthy appearance. In July of that year he was suddenly seized with severe pain in the upper half of the chest on the right side. A brother physician examined him but could not detect any abnormality. In the course of a week he felt entirely well. The following December, suddenly and without apparent cause, he had another similar attack of intense pain. This time, however, it was distinctly localized in an exquisitely tender area over the third right rib in front. But just as before, the pain soon disappeared. The urine at this period presented no abnormal change.

During the year 1880 paroxysms of intense pain, referred


I'Loc. cit.

20 See Hammer, Virch. Arch., 137, S. 300.

'" Contributions to the Science of Med. dedicated to Dr. W. H. Welch. The Johns Hoplcins Press, Baltimore, 1900.


to numerous ribs and other parts of the trunk as well aa to the right patella, alternated with periods of comfort, during which he could attend to his busy practice. Any unusual muscular exertion, however, would call forth violent pain.

In March, 1881, following a slight contusion, an exceedingly painful and tender area appeared over the fifth left rib. A flat elevation could be outlined over the costal surface, but in the course of a few weeks both pain and elevation had disappeared only to recur later in other ribs and bones. During the latter part of this year and for the first time, the urine gave a heavy precipitate with nitric acid. The patient had lost considerable weight and looked ill.

The early months of 1882 were passed in much the usual way. When confined to bed by the unbearable bone pain and neuralgias his condition was truly pitiful. Every movement aggravated and intensified his great suffering. Besides, his nights were sleepless and paroxysms of tachycardia and cardiac oppression added to his discomfort. The summer of this year saw an improvement so that he was able to resume to some extent his favorite pastime, hunting. But the improvement was temporary, for before the year closed the painful attacks returned, the anginal paroxysms were renewed and in addition he was troubled with nausea. The poor doctor's suffering continued during the following two years, 1883 and 188-±. What with the pain in the ribs and sternum, the anginal attacks and nausea, paresthesias in the lower limbs, visceral pains and obstinate insomnia, his state had become deplorable.

In 1885 a kyphotic bowing of the upper thoracic vertebral column was noted. In December of this year Kahler saw him for the first time. He was then cachectic; his spinal column presented a dorsal kyphosis. Standing, his face pointed down; the trunk appeared markedly shortened compared with the length of the extremities. There was marked tenderness on palpating certain circumscribed areas over the body of the sternum and the ribs. Careful and repeated examinations of these regions disclosed very slight elevations of the bony surfaces. The urine exhibited the reactions of albumosuria.

The doctor's condition grew progressively worse in 1886. Pain recurred in various bones of the trunk and neuralgias in the nerves of the extremities. The kyphosis increased, the thorax became deformed, the sternum projecting forward and the ribs appearing correspondingly bent. In 1887 the inguinal glands were found enlarged. The sense of hearing had been diminishing for several years, but now its impairment was very marked. A double labyrinthine affection was diagnosed. In April of this year a well-marked crepitus could be elicited over the third right rib by_ pressure and by the respiratory movements. A tumor appeared in the right supraspinous region.

Finally, deformed, deaf and suffering, the patient was released by death in August, 1887.

I have spoken of the clinical diagnosis in the case as well as the anatomical examination. The essential features of this type of the disease are the paroxysms of pain referred


44


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[No. 119.


to the bones, the great deformity of the skeleton of the trunk, the cacliexia and the presence of Bence Jones' albumosuria. These are the eases that have been mistaken for osteomalacia, but in no example of true osteomalacia have these urinary reactions been discovered, so that the albumosuria suffices for differentiation."

The patient shown you to-night illustrates a second class. Here the tumors are visible and there are pathological fractures. In Bozzolo's patient the tumors appeared on the arms, shoulders and ribs. A diagnostic difficulty arises in deciding whether these timiors are metastases of a primary growth latent in some distant organ or multiple primary tumors of the bone. The albmnosuria not only answers this question but at the same time determines the nature of the new growth. In no instance of multiple metastatic osseous tumors have Bence Jones' reactions been present and the new growth has invariably been a myelogenous sarcoma, a myeloma.

In a third division must be placed the cases of multiple myeloma in which the bone symptoms and signs are vague or even absent. To this class belongs the ease of Ellinger:

His patient was a man 45 years of age who was admitted to Lichtheim"s clinic in October, 1897. For about six weeks he had had, almost daily, chilly sensations, fever and sweats. His appetite failed and he felt ill. He did Jiot complain of pain in any part of the body.

The man was fairly well nourished and presented slight jaundice and fever. The urine contained some albumin and biliary pigments. The jaundice diminished but the fever persisted; the patient grew weaker and paler. Four weeks after admission Bence Jones' reactions were discovered in the urine. Two weeks later the clinical picture was clearly one of progressive anaemia with hemorrhagic sputum and effusions into the subcutaneous tissue, the joints and serous cavities. In a few days this condition led to the exitus lethalis. Just before death it was noted that percussion over the sternum was painful. No diagnosis was made. Post mortem, a multiple myeloma was discovered.

In cases such as Ellinger's the progressive anaemia and its concomitants occupy the attention of the observer, and, unless the significance of the albumosuria is recognized, a diagnosis is impossible.

A transition from this class of multiple myeloma to those in which the bone lesions are evident is illustrated by Dr. Iglehart's patient. Macintyre's case, which formed the basis of Bence Jones' observations, belongs to this variety of myeloma. Macintyre wrote that " the affection to which it bore the nearest resemblance was a severe attack of lumbago or sciatica." But he adds it was evident " that suffering so intense must have a deeper seat and more formidable cause than mere muscular or neuralgic rheumatism." In discussing the diagnosis of maladies of the bone, he remarks that their nature is usually, not suspected until they are fully developed and until deformities or fractures are present. He adds very wisely : " It is this considera


"See Kahler, loc. cit.


tion that, in my mind, invests the properties of the urine, voided by this patient, with their chiefest interest."

In relating the clinical histories of multiple myelomata, I have mentioned several of the anomalous symptoms — fever, nausea, attacks of visceral pain, neuralgias and paresthesias.

The remarkable nervous symptoms have been considered in detail by Senator. "" His patient presented a double hypoglossal paralysis, anaesthesia in the region supplied by the third division of the trigeminal nerve and a paresis of the arytenoideus. These curious phenomena so dominated the clinical aspect of the case that in spite of the presence of albumosuria a diagnosis was not reached. The autopsy disclosed myelomata, but no appreciable change in the nervous sj'stem was found. Senator regards the ansmia in such cases as the etiological factor, basing his opinion on the researches which have demonstrated that not only slight functional disturbances in the nervous system but even gross alterations in its structure may occur in the course of a profound auasmia.

I have attempted to show you how manifold is the symptomatology of multiple myeloma. You may readily imagine the obscurity of the cases in which the osseous system presents no localizing symptoms.

It is as a contribution to the diagnosis of these obscure cases of a pernicious bone disease that I have presented this preliminary report and emphasized the importance of Bence Jones' nllmmosuria.

Discussion.

De. Welch. — The most interesting recent contribution to the pathological anatomy of so-called multiple myelomata is the paper of Dr. James H. Wright, to which Dr. Hamburger has referred. It seems clear that the lesions of the bones in this disease are not genuine tumors in the Cohnheim sense, and that the multiple nodules are not to be regarded as metastatic tumors secondary to a primary one. The growths in the bones have much in common with the infectious tumors. In the case reported clinically by Dr. Fitz and anatomically by Dr. Wright, the tumor-cells were predominantly plasma cells. It remains for future investigations to determine whether in all cases these multiple myelomata, which, as well known, have been described under a great variety of names, present the special histological characters so well described by Dr. Wright. If so, they would belong to the class of new growths, first designated by Unua as plasmomata. To this class belong many of the so-called infectious grauulomata.

I have recently examined a small tumor of the palpebral conjunctiva sent to me for diagnosis and have found that the tumor is composed almost whoUj' of plasma cells, mixed with so few ordinary lymphoid cells that transitions between the latter and plasma cells are not easy to find. Probably some of the tutnors which we formerly were accustomed to


»3Berl. Kl. Wochenscbr., 1899, Bd. 36, S. 161.


Febhuaey, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


45


diagnose as l3aiipho-sarcoma, round-celled sarcoma, etc., will be found to be plasmomata.

De. Atkinson. — Have these cases of albumosuria with bone lesions any connection with the cases of osteitis deformans reported some years ago by Paget and recently by Smith (Ergebnisse der AUgemeinen Pathologic und Pathologischeu Anatomie des Menschen und der Thiere); the disease coming on insidiously with enlargement of the bones, gradual increase in the size of the head and shortening of the body through degeneration of the bones and bowing of the legs? In a certain number of those cases of osteoporosis


and osteosclerosis the end has been cancer of the bones, and I suspect albumosuria might have been found if looked for. I saw last spring an individual with typical osteitis deformans but he showed no lumps on the bones and no such reaction in the urine.

Dk. Hamburger. — I know of no relation between the two conditions and of no literature on the subject.

Note.— The colored woman died February 1, 1901. Post mortem^ myelomata were found in the skull, left scapula, both clavicles, the sternum, the right ilium and neck of the right femur.

Examination of Dr. Iglehart's patient now shows a slight but definite elevation over the ninth left rib in front.


RErORT OF A CASE OF FULMINATING HEMORRHAGIC INFECTION DUE TO AN ORGANISM

OF THE BACILLUS MUCOSUS CARSULATUS GROUP.

By Gkorge Blumer, M. D., and Arthur T. Laird, M. D.

(From the Bcmhr Hijijknic Laboratory, Alhaiitj, N. Y.)


The subject of hemorrhagic infection in man, due to organisms of the Bacillus mucosus capsulatus group, has been so recently discussed in this country by Howard ' that it seems hardly necessary to more than briefly review the subject in reporting a new ease. The cases hitherto reported have varied from one another to a considerable degree in their intensity, and to a certain extent in the character of their lesions. Whilst in some cases the lesions were purely septicemic and the infection of the cryptogenic type, in other instances the process seems to have started as a local infection, though quickly becoming generalized. Thus the cases of Bordoni-Ulfreduzzi," Von Dungern' and Kolb * were of the character of general infections without special points of origin, the cases of Tizzoni and Giovanni ' seemingly originated from the skin, those of Babes ° from the bronchi, and in our own case the intestinal tract was in all probability the primary seat of infection. In all instances the essential feature of the process was its hemorrhagic character.

The following ease occurred in the practice of Dr. D. L. Kathan of Schenectady, to whom we are indebted for the history, and who kindly obtained permission for the autopsy. The case seems worthy of record on account of the relative rarity of this form of disease.

A. F., aged 20, a machinist.

Family Histonj. — His father died of cancer of the kidney at 55. His mother died of pulmonary tuberculosis at 30. Two sisters are alive and well. There are none dead in the family.


1 Howard : .Journal of Experimental Medicine, vol. iv. No. a, 1899.

'Bordoni-Ua'reduzzi: Zeitsehrift fiir Hygiene, 1888, Hft. iii.

3 Von Dungern: Centralblatt fiir Bakteriologie, Bd. xiv, No, 17, 1893.

"Kolb: Arbeiten aus den Kaiserliche Gesundheitsamte, Bd. vii, 1891.

5 Tizzoni and Giovanni: Ziegler's Beitriige, vi, p. 201, 1889.

6 Babes: Archives de Medecine Expcrimentale, tome v, 1890.


Past History. — The patient has always been unusually strong and athletic. His habits are excellent.

Present History. — The patient had been in perfect health and working every day until October 19, 1900. On the morning of that day he went to work as usual after a hearty breakfast. He returned just after noon, not having eaten his dinner. He complained of feeling ill, and went directly to bed. He began to vomit and purge, the bowels moving every few minutes. He complained of pain in the abdomen. Examination showed that there was no local abdominal tenderness, no tympanites. The temperature was 103° F. The pulse was 120.

At the end of twelve hours he was seen again. At that time the bowels were only moving about once in four hours, and the vomiting had practically ceased. The temperature was subnormal. The hands and feet were cold and cyanosed. The face had a pinched appearance.

At the end of 24 hours there was confusion of mind, and the patient was in a state of complete collapse. Death occurred at the end of 36 hours, there having been at no time the slightest tendency towards recovery.

The autopsy was made six and a half hours after death in cool weather.

The following notes are abstracted from the protocol:

The body is 171 cm. long, powerfully built, and well nourished. Eigor mortis is well marked. There is extensive post-mortem lividity of the legs, arms and trunk. The surface is pale; there is no oedema. The lips and finger-tips are cyanotic. The mucous membranes are pale. The muscles are exceptionally well developed and normal looking. The peritoneal cavity is dry, both layers of the peritoneum being smooth. The omentum and appendix are normal.

The heart is in every way normal except for the presence of numerous subepicardial hemorrhages of small size, and slight cloudy swelling of the musculature.


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[No. 119.


The lungs show numerous subpleural hemorrhages with congestion, and a few elevated, finely granular, deep-red areas, suggesting fresh broncho-pneumonia.

The spleen is much enlarged, measuring 16 X 10.5 X 5 em. On section it shows numerous hemorrhages into the pulp, and marked swelling of the Malpighian bodies.

The liver is enlarged, soft, and markedly cloudy.

The kidneys both present the same appearances, being much softer than normal, with their cortices pale and swollen. There are a few submucous hemorrhages beneath the mucous membrane of the pelves.

The adrenals, bladder, prostate and pancreas are normal.

The stomach shows a few submucous hemorrhages, but is otherwise normal.

The solitary follicles throughout the small intestine are markedly swollen, and in the ileum Payer's patches are also affected. The mucosa of the intestine between the swollen lymphatic apparatus is congested and in places markedly hemorrhagic; in places the Peyer's patches contain discrete hemorrhages.

The large intestine is normal.

The mesenteric glands are swollen, some of them being pale, others hemorrhagic.

The brain and cord could not be examined.

MiCEOscopic Examination.

The heart-muscle shows uothiug beyond an excessive number of polymorphonuclear leucocytes in the vessels.

The lung shows in places groups of alveoli containing red blood-corpuscles, with a few desquamated epithelial cells and an occasional dust cell. The blood-vessels in this organ also contain an excessive number of polymorphonuclear leucocytes.

The liver shows marked cloudy swelling of its cells, with occasional single-cell necroses. The portal vessels contain a great excess of leucocytes, which have wandered out in quite large numbers into the periportal connective tissue.

The spleen shows great dilatation of all its blood-spaces with blood. In the pulp spaces many large phagocytic cells containing red corpuscles are made out. There is no distinct evidence of proliferation of the endothelial cells lining the splenic vessels.

The kidneys show marked cloudy swelling of the parenchymatous cells. The capillaries, especially those of the glomeruli, are crowded with polymorphonuclear leucocytes. Two distinct types of localized lesions are to be made out in these organs. In places in the cortex are localized collections of polymorphonuclear leucocytes invading the tubules and the intertubular connective tissue. In the medulla near its junction with the cortex are areas in which the intertubular connective tissue is quite oedematous-looking, and is infiltrated with a few polymorphonuclear leueoeyteB, and a moderate number of cells with round extracentral nuclei which have the staining reactions of plasma cells. These cells evidently come from the neighboring blood-vessels


which contain many of them. No casts are seen in the tubules.

The changes iu the intestines are partly inHammatory and partly proliferative iu character. The inflammatory changes are most marked in the interglandular tissue and consist in an infiltration with polymorphonuclear leucocytes accompanied by hemorrhage. The proliferative changes are most marked in the lymphatic apparatus. They consist in the appearance of large cells of an endothelial type amongst the lymphoid cells which are greatly decreased in number. These large cells have distinct phagocytic properties and contain in places deeply stained particles of nuclear substance, presumably portions of lymphoid-cell nuclei. The blood-vessels in and near the lymphatic apparatus show proliferative changes in their endothelium. The proliferated cells almost block the capillaries in places, whilst in other places fibrin-formation with complete thrombosis has occurred. The changes resemble in every way those described by Mallory in typhoid fever, though less in degree.

The changes in the mesenteric lymph glands are essentially the same as those in the lymphatic apparatus of the intestine.

Sections of the various organs examined for microorganisms show short thick bacilli in the blood-vessels of the lung and in the areas containing exudate. They are also found in the sections of intestine and in the mesenteric glands. The organisms are, as a rule, free between the cells, but occasionally are found in large numbers in polymorphonuclear leucocytes. These organisms resemble those subsequently isolated from the mesenteric glands and the lung.

Cultures were made at the time of the autopsy from the heart's blood, lung, liver, spleen, bile and a mesenteric lymph gland.

All of these remained sterile after several days in the thermostat at C. 37°, except the culture from the lung, and that from the mesenteric gland. The tubes from each of these organs showed numerous colonies of a single organism which presented the following morphological and cultural characteristics. Unless otherwise stated, cultures were made on standardized media with an acidity of 1.5 according to Whipple's scale:

Morphology. — In young cultures grown at the temperature of the thermostat the organism appears as a bacillus, varying from 1 to 4 microns in length and averaging 0.5 micron in width. The organisms occur singly or in pairs or chains of 2 or 3 elements. The ends are rounded, many of the short forms appearing almost oval. Occasional thread-like forms are observed. Irregularly shaped forms, which stain unevenly, are seen in old potato cultures (6 days at C. 3638°). The organism stains well with aqueous methylene blue (1 :9), better with Loffler's methylene blue. Bipolar staining is sometimes noticed in the short forms. The organism is decolorized by Gram's method.

A capsule is to be made out by Welch's method in smears from animal tissues, and is occasionally seen in blood-serum cultures; it is not uniformly present.


February, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


47


No spore-formation is observed.

Flagella are not present, and the organism seems to be non-motile.

The organism grows best aerobically, but is also capable of growth under anaerobic conditions. It grows on media as follows :

Agar Slant. — After 24 hours there is a luxuriant, elevated, porcelain-white growth along the line of inoculation; the edge is tinely serrated. There is abundant growth in the water of condensation. The growth is not markedly viscid. It has no odor.

Agar Plates. — The superficial colonies are circular, elevated, about 2 mm. in diameter with a sharply defined margin and a snow-white color. Under the low power they are made up of a coarsely granular periphery surrounding an opaque center. The deep colonies are spherical or lensshaped, white, about 0.5 mm. in diameter, and microscopically finely granular in structure.

Gelatin Plates. — The surface colonies are small, not more than 1 mm. in diameter; they show little tendency to spread and are circular, elevated, white, and denser at the center than at the periphery. Under the low power they arc yellowish, coarsely granular, and show a concentric arrangement and finely serrated edges. The deep colonies are spherical, opaque and finely granular.

Gelatin Stah. — There is a delicate growth along the line of the stab, and a slight circular non-elevated growth on the - surface. No liquefaction is produced.

Potato. — After 24 hours there is a luxuriant, spreading, moist, elevated, brownish-yellow growth. The potato is discolored a brownish yellow. There is no gas production.

Dunham. — Is imiformly cloudy after 24 hours. No pellicle is formed. Later there is an abundant grayish-white sediment, which on agitation diffuses evenly through the liquid, and is not stringy.

Blood-serum. — The growth is similar to that on agar. There is no liquefaction of the medium.

Indol-Formation. — The organism produces indol in dextrose free bouillon after 4 days at C. 37°.

Gas-Formation. — Several different tests were made with each medium. Gas noted after 72 hours at C. 37°.

In 1 per cent glucose bouillon, 45-60 per cent of gas.

H f

In 1 per cent lactose bouillon, 45-55 per cent of gas.

H f

In 1 per cent saccharose bouillon, no gas is found as a rule. On one occasion a trace was noticed.

Pathogenesis.— 25 minims of a 72-hour bouillon culture were injected subcutaneously into the abdominal wall of a full-grown guinea-pig. The animal died within 24 hours. The autopsy showed slight swelling at the point of inoculation, swelling of the nearest lymph glands with hemorrhages, an early serofibrinous peritonitis, and hemorrhages into the kidneys and beneath the pleura. The intestinal lymphatic


apparatus was swollen and surrounded by congested mucous membrane. The organism was found in coverslips from the point of inoculation and the blood, at times encapsulated. It was recovered in pure culture from the seat of inoculation, blood and spleen.

25 minims of a 72-hour bouillon cultui'e were inoculated into the peritoneal cavity of a full-grown guinea-pig. The animal died within 24 hours. The autopsy showed that there was no local or glandular reaction. There was a distinctly viscid seropurulent peritoneal exudate. The spleen was enlarged. There were hemorrhages into the adrenals and beneath the pleura. There was a fresh right-sided pleurisy. The organism was seen in the smears from the blood and peritoneal cavity, many of the organisms from the latter place having a distinct capsule. It was recovered in pure culture from the heart's blood, spleen and peritoneal exudate.

A full-grown rabbit was inoculated into the ear-vein with 25 minims of a 72-hour bouillon culture. It died within 20 hours. The autopsy showed no reaction at the point of inoculation. There was a fresh fibrinous peritonitis. The spleen was enlarged, soft and congested. The liver and kidneys were also congested, as was the mucous membrane of the uterus. The organism was recovered from the heart's blood, spleen and peritoneum in pure culture.

Anatomical Diagnosis. — Hemorrhagic infection due to an organism of the Bacillus mucosus capsulatus growth; acute hemorrhagic follicular enteritis; acute spleen tumor with swelling of the Malpighian bodies; cloudy swelling of the liver and heart muscle; acute infectious and interstitial nephritis; hypostatic congestion of the lungs.

We have placed the organism isolated in this case in the group of Bacillus mucosus capsulatus, since whilst it differs in minor points from similar organisms already described, it corresponds in the following features laid down by Fricke ' for the identification of members of this group. Howard, quoting from Fricke, states as follows:

" The more important common characteristics of this group are the morphology, plump, medium-sized, plemorphic rods; the presence of capsules, readily demonstrable in the animal body and sometimes in cultures; lack of motility and of spores; failure as a rule to stain by Gram; the rapid, luxuriant, elevated, viscid white growth upon the surface of solid media; absence of liquefaction of gelatin; and pathogenicity, usually in the form of septicaemia, but with striking variations for difi^erent animals, and for different members of the group."

In comparing this organism with a culture of Howard's bacillus of hemorrhagic septicaemia which he kindly sent us, and with a culture of Pfeiffer's capsulated bacillus, which we obtained from the Laboratory of Hygiene of the University of Pennsylvania, the growth of the three organisms on ordinary media was almost identical. Our organism, however, failed to produce gas in saccharose bouillon, and


'Fricke: Zeitscbrift fiir Hygiene, Bd. xxiii, 1896.


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[No. 119.


produced indol constantly. Both Pfeiffer's and Howard's organisms produced abundant gas in saccharose bouillon. We were never able to detect indol in cultures of Pfeiffer's organism, though in one out of several cultures of Howard's bacillus we obtained a faint indol reaction. Pfeiffer's organism was furthermore distinguished by the fact that on solid culture media the growth constantly exhibited a mucilaginous consistency so that it adhered to the needle and pulled out into threads. In its failure to produce gas in saccharose bouillon our organism seems to differ from all of the so far


recorded ones. The various organisms of this group studied by Strong ° all produced gas in saccharose, as did the organisms recently studied by Howard."

The case is of interest pathologically on account of the proliferative changes in the lymphatic apparatus of the intestine, and clinically on account of its exceedingly rapid course.


8 Strong: Journal of the Boston Society of the Medical Sciences, vol. iii, ISnSI.

' Iloward: Journal of Experimental Medicine, vol. v, no. 2, 1300.


INTRODUCTORY NOTE TO DRS. DURHAM AND MYERS'S REPORT.


The following short summary was sent to me by Dr. Durham with the suggestion that it appear in a medical journal in this country. In justice both to the English Commission and to the American Commission, it should be stated that the comment in paragraph 11 is made without knowledge of the later fuller experiments and important results recently published by the latter commission.

Dr. Durham and Dr. Myers spent several days in Baltimore last July on their way to Para, Brazil. All of us who met these gifted young investigators retain the pleasantest remembrance of them personally and were impressed with their fitness in scientific training and ability for the work which they were about to undertake. A little over a month ago came the sad news that Dr. Myers had succumbed to an attack of yellow fever. Dr. Durham, who contracted the disease at the same time, has fortunately recovered, and at the date of his writing (January 29) was about to resume the study of yellow fever.


The death of Dr. Myers at the outset of his career is a severe loss to medical science. His published contributions show thorough scientific training and marked originality, and, although extending over a period of only about three years, are valuable additions to knowledge, giving promise of much fruitful activity as an investigator. They relate mainly to problems of immunity, especially to immimity from snake-venom and from proteids.

Both Lazear of the American and Myers of tlie English Yellow Fever Commission have laid down their lives in the search for means of prevention, based upon better knowledge of the causation, of one of the most baffling and terrible scourges of mankind. How much more glorious is the cause to which these bright young lives were sacrificed than any for which nations are in arms to-day!

WiLLi.vM H. Welch.


ABSTUCT OF INTERIM REPORT ON YELLOW FEVER BY THE YELLOW FEVER COMMISSION OF

THE LIVERPOOL SCHOOL OF TROPICAL MEDICINE.

By Herbert E. Durham and the late Walter Myers.


Note. — The completion of the interim report of which this is an abstract was interrupted by the onset of attacks of yellow fever in both of us. The loss of my much lamented colleague renders it advisable to submit this shortened report only for the time being. — H. E. D.

1. Sufficient search reveals the presence of a fine, small bacillus in the organs of all fatal cases of yellow fever. We have found it in each of the 14 cadavers examined for tlie purpose. In diameter the bacillus somewhat recalls that of the influenza bacillus; as seen in the tissues, it is about 4//. in length.

2. This bacillus has been found in kidney, in spleen, in mesenteric, portal and axillary ' lymphatic glands taken from yellow-fever cadavers directly after death. In the contents of the lower intestine apparently the same bacillus is found often in extraordinary preponderance over other micro ' We find these constantly enlarged and much injected, though whether this is specific we are not able to say.


organisms. Preparations of the pieces of " mucus," which are usually if not always present in yellow-fever stools, at times may present almost the appearance of " pure culture."

3. Preparations of the organs usiuilly fail to show the presence of any other bacteria, whose absence is confirmed by the usual sterility of cultivation experiments.

4. It is probable that this same bacillus has been met with, but not recognized, by three other observers. Dr. Sternberg (Eeport on Etiology and Prevention of Yellow Fever, 1890) has mentioned it, and he has also recorded the finding of similar organisms in material derived from Drs. Domingos Freire and Carmona y Valle, but he did not recognize its presence frequently, probably on account of the employment of insufficiently stringent staining technique.

5. It is probable that recognition has not been previously accorded to this bacillus by reason of the difficulty with which it takes up stains (especially methylene blue), and by


February, 1901.]


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reason of the difficulty of establishing growths on artificial media.

6. The most successful staining reagent is carbolic fuchsin solution (Ziehl), diluted with 5 per cent phenol solution (to prevent accidental contamination during the long staining period); immersion for several hours, followed by differentiation in weak acetic acid. Two-hours staining period may fail to reveal bacilli, which appear after 12 to 18 hours. The bacilli in the stools are often of greater length than those in the tissues, and they may stain rather more easily; naturally the same is true of cultures. Some of our specimens have already faded.

7. Since the bacilli are small and comparatively few in numbers, they are difficult to find. To facilitate matters at our last two autopsies (14th and 15th), a method of sedimentation has been adopted. A considerable quantity of organ juice is emulsified with antiseptic solutions, minute precautions against contamination and for control being taken; the emulsion is shaken from time to time and allowed to settle. The method is successful and may form a ready means of preserving bacteria-containing material for future study. The best fluid for the purpose has yet to be worked out; hitherto normal saline with about ^ per cent sublimate has been employed.

8. Pure growths of these bacilli are not obtained in ordinary aerobic and anaerobic culture tubes.

9. Some pure cultures have been obtained by placing whole mesenteric glands (cut out by means of the thermocautery) into broth under strict hydrogen atmosphere. In


vestigation into the necessary constitution of culture media for successful cultivation is in progress.

10. Much search was made for parasites of the nature of protozoa. We conclude that yellow fever is not due to this class of parasite. Our examinations were made on very fresh organ jiiices, blood, etc., taken at various stages of the disease, with and without centrifugalization, and on specimens fixed and stained in appropriate ways. We may add that we have sometimes examined the organs in the fresh state under the microscope within half an hour after death.

11. The endeavor to prove a man-to-man transference of yellow fever by means of a particular kind of gnat by the recent American Commission is hardly intelligible for a bacillary disease. Moreover, it does not seem to be borne out by their experiments nor does it appear to satisfy certain endemiological conditions. It is proposed to deal more fully with the endemiology and epidemiology of the disease on a later occasion.

12. We think that the evidence in favor of the etiological importance of the fine small bacillus is stronger than any that has yet been adduced for any other pretended " yellowfever germ." At the same time there is much further work to be done ere its final establishment can be claimed. The acquisition of a new bacterial intestinal inhabitant would explain the immimity of the " acclimatised."

Para, Brazil, Januarv 28, 1901.


'We have found this sometimes useful in examining the blood of ague patients.


SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.

Vol. XII - No. 120.

BALTIMORE, MARCH, 1901.

Contents - March

  • The Genesis of Carciuoma of the Fallopian Tube in HyperpUistic Salpingitis, with Report of a Case and a Table of Twenty-one Reported Cases. By E. R. Le Count, M. D., .5.5
  • Report upon a Case of Gonorrlia'al Endocarditis in a Patient Dyins; iu the Puerperium ; with Kefereuce to two Recent Suspected Cases. By Norman MacLeod Hakhis, M. B., and \Vm. M. Dabney, iM. D., t!8
  • An Experimental Study concerning the Relation which the Prostate Gland Bears to the Fecundative Power of the Spermatic Fluid. By Geohge Walkeu, M. D., 77
  • Summaries or Titles of Papers by Members of the Hospital and Medical School Staff Appearing Elsewhere than in the Bulletin, 80

Further Observatious on Epincidirin. By .John .J. Ahel, M. D., 80


THE GENESIS OF CARCINOMA OF THE FALLOPIAN TUBE IN HYPERPLASTIC SALPINGITIS, WITH REPORT OF A CASE AND A TABLE OF TWENTY-ONE REPORTED CASES.

By E. K. Le Count, M. D., Assistant Professor of ralhology, Rush Medical CoUege.

{From t/ic Pul/iuldr/iral L'thiirndirij «/ Itnsh Medical College.)


Among theoretical conceptions of pathological processes to which disease is attributable are certain ideas that have at their inception the distinctness of a silhouette. Witli the advancejiient of knowledge, the margins of certain notions lose their definiteness and we find various processes uniting insensibly at their boundaries. The idea that necrosis means death of tissue remains firmly planted, but the exact limitation of its import is considerably blurred when the process of gradual death is screened behind tlie caption of atrophy. Any attempt deserves approval that


has for its object the segregation and classification of morbid processes that lie in the boundary zone. It seems, however, that as time advances the narrow distance now separating the process of tissue hyperplasia from that concerned in the development of benign tumors will not be increased. Lubarsch,' after commenting on the close connection between tumors and infectious processes, notes this difficulty in the followins: words: " Suchte man daher nach anderen un


Ergebnissed. alls;. Path. ii. path. Anat., 18!).5, ii, p. 'i90, Wiesbaden.


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terschiedeiien Kriterien, so maclite sicli eine weitere Sehwierigkeit, die Abgrenzung gegeiiiiber die Hyperplasie bemerkbar." Still, it is evident that if a process of questionable character midway between tumor and hyperplasia can be traced to an inflammatory origin, its position is no longer in doubt. It must of necessity be considered as hyperplasia or the meaning of the word tumor will require modiiication. In lesions of such uncertain species, in which the inflammatory origin is manifested by simply one of the inflammatory phenomena, viz., that of proliferation, the question seems surmountable in only one way — to admit without further discussion the existence of a firm bond uniting them. Such a solution of the problem is rendered easy by finding lesions which represent all transition stages from one process to .another. An example of this kind is reported by W. W. Van Arsdale: ' a growth developed on the upper right arm two days after several blows received during a sparring bout. A fluctuating swelling that increased the circumference of the arm 10 cm. was present two days aftei injury; one month later the mass had decreased to one-third its former size, but it had become hard and inunovable. Two months after the injury, a growth 9 cm. in length and 3 cm. in its other diameters was chiseled from lietween the biceps and branchialis anticus; it was found to jxissess an outer shell of bone 1.5 cm. thick, the jieriosteuni l)eing closely adherent to its e.\terior, and a cavity filled with dark partially coagulated blood; its outer wall was true bone and its cavity devoid of bone-nuirrow proper; its inner wall was porous vascular bone.

It seems reasonably certain that In tiiis case the clot of a subperiosteal haemorrhage became ossified at least in its outer part. According to Klebs, the process of bone-formation in this " Ossifying hajmatoma " would serve as an example of hyperplasia; for, he states, the line between hyperplasia and tumor-growth may be determined to some extent by the preponderance of the former in scars and granulation tissue and its proneness to spontaneously disappear. The growth would be inflammatory in origin, for the unabsorbed blood would excite an inflammation in the surrounding parts (Cohnheim).* According to Lubarsch," the apparently autonomous hyperplastic growths almost without exception follow inflammatory excitants. Notwitlistanding these opinions, it is unreasonable to suppose that had ossification been allowed to continue throughout the entire coagulum, that the mass of new bone would ever have disappeared spontaneously; there would have resulted an osteoma — a benign tumor. Surgeons are well acquainted with the permanent character of the bony hyperplasia which occurs in a luxuriant callus and the osteomas that develop in the biceps and pectoral muscles from the kick of a gun (Tillmanns).

Another instance of lesions which represent transitions between hyperplasia and benign tumor is furnished by mul


5 Ann. Siirs., 1893, xviii, p. S, Phil.

3 Die allt;. Patliologie, etc., ii, p. 491, 1889, .Jena.

■• Vorlesungeu iiber allg. Pathologie, p. 393, 1882, Berl.

5L. c., p. 397.


tiple adenomata of the liver. In proof of their mediate position is the fact that equally good authorities are arranged on opposite sides: Weichselbaum, Eindfleisch, Chiari and Kretz classify the condition with simple hyperplasia; Lubarsch, Thoma, Poufick and Eppiuger with adenomata. Orth seriously considers the question of tumors arising from multiple nodular hyperplasia of the liver, and Schmieden,' in a recent review of the connection which exists between these lesions, declares that a sharp division between adenoma and hyperplasia in the liver cannot be made. lie claims to have seen, as Van Heukelon did before him, the transition forms between hypertrophied liver cells and tumor cells. The relationship between hyperplastic processes and tumor is more important when it has to do with cells that possess great jDOwers to proliferate and regenerate, c. (J., surface epithelium and the epithelium of superficial glands. In discussing this subject Birch-llirschfeld ' makes the statement that such atypical hyperplastic growths show in the excess of their regeneration certain points of similarity to tumors, and it may be accepted that they may become changed into tumors; he also states" that the possible occurrence of growths which represent transition stages between hyperplasia and tumor can not be excluded.

The effect of a productive inflammation or inflamiuatory hyper]ilasia upon mucous linings is either a dilfuse and uniform thickening nr the formation of the isolated jtolypoid outgrowths. As tlic gross appearances change from a diffuse process to dispersed or widely scattered growths, the likelihood of the inflamuuitory origin lessens, for the conception of a tumor is connected with the local limitation of its early growth (Thoma). But to this there are exceptions, for " the inflammatory new growths, which are due to atypical proliferation of epithelium, fend to form either single, tumorlike jn-otuberant growths or multiple growths over a considerable surface" (Birch-Hirshfeld).

The confusion which attends the wonl jiajiilloma is no more attributable to its diversity of structure than to the question of its proper position in regard to tumors and the hyperplastic inflammations. Birch-Hirschfeld '° states thai in mucous membranes a diffuse or circumscribed polypoid thickening may result from chronic catarrhal inflammation; also, that in the nose" combinations of papilloma and hyperplasia of the mucosa occur. Klebs '" uses the isolypi of the stomach to illustrate the effect of hyperplastic inflammation in the production of papilloma. In the statement by Orth " concerning the papillomata of the Fallopian tube, that it is difllcult to determine with certainty to what extent they are caused by inflammatory growths of the folds of the mucosa, we have further evidence of the confusion.


6 Lelirbueli der spec. path. Anatomie, i, p. 9.')7, 1S97, Berl. 1 Arch. f. path. Anat. (etc.), cli.K, p. 290, 1900, Berl.

8 Grundriss der allg. Pathologie, p. 144, 1892, Leipzig.

9 Lehrbuch der path. Anat., i, p. 180, 1890, Leipzig.

10 L. c, p. 137.

" Lehrbuch der path. Anat., ii, p. 4.'i0, 1894, Lcijizig.

12 L. c, p. fil.5.

i^Lehrbnch der spec, jiath. Anat., ii, p. .539, 1889, Berl.


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Such uncertainty of classification leads naturally to the use of terms which are devised to bridge over the difficulty. Such a title, alluding both to the process of hyperjilasia and to the admixture with tumor, is used by Hauser" in his report of a case of " Polyposis intestinalis adenomatosa." In' this case there were disseminated polypi consisting largely of atypical epithelial growths not only throughout the intestinal canal but also in the stomach. Hauser refers to three other similar cases. Petrow " has added another in which there were numerous single or clustered, large and small polypous growths in the stomach and the entire intestinal canal, together with every evidence of a severe chronic inflammation in the mucous coats involved.

Quenu and Landel '" have recently collected 43 cases in which the large intestine was the seat of a more or less extensive polypous hyperplasia. From the frequent history of diarrhrea, these authors believe that the process has its origin in inflammatory conditions, and this opinion is reached after a thoughtful consideration of the possibility that the intestinal disturbances might be secondary to the multiple adenomata. In a previous article by the same authors " there is even less doubt displayed respecting the identity of pedunculated adenomata of the rectum with hyperplastic processes, for the statement is made that " they are more or less directly dependent upon an inflammatory reaction."

Sklifossowsky," after describing two benign papillai'v tumors in the mucous lining of the stomach, states that they originated from a hyperplasia of the mucous coat due to long-standing irritation; he likens them to the knob-like projections of the Stat mamelonne. His interest in these growths was largely due to the fact that all transitions were found in them between the diffuse thickening of gastritis proliferans and the tumors described.

Further evidence is not necessary to illustrate the fact that hyperplastic processes in the mucous lining of the gastro-intestinal tract, like those of the liver, are closely allied to the processes of tumor-development; or that there are certain interposed lesions which might be accepted as proof of the continuity of processes having as their onset chronic inflammation, and, as their termination, tumorgrowth. The analogy will be more complete with the demonstration of cases such as are hinted at by Birch-Hirschfeld '° in the following proposition : " It is probable, but not proven, that certain forms of primary carcinoma of the liver may have their origin in a further atypical development of such liver adenomata." The fact that the hyperplasia of the gastro-intestinal mucosa has, as its end product, the


!■' Deutsebes Arch. f. klin. Med., Iv, p. 429, 189.5, Leipzig.

'» Bolnitsch. gas. Botklna, 1896, St. Petersburg. From the summary of Russian literature by Maximow and Korowin, Ergebnisse d. allg. Path. u. path. Anat., Lubarsch and Ostertag, v, p. 73.5, 1898, Wiesbaden.

i^Les polyadenomes du gros intestine. Rev. de Chir., xi.v, p. 405, 1899, Paris.

1' Rev. de gynec. et de chir. abd., ii, p. 484, 1898, Paris.

iSArch. f. path. Anat. (etc.), cliii, p. ISO, 1898, Berl.

"L. c, p. 743.


evolution of malignant neoplasms, leaves no room for controversy such as has been noted with regard to multiple adenomata and nodular hyperplasia of the liver.

In 42 cases gathered by Quenu and Landel of polypous hyperplasia of the colon, there were 20 in which a carcinoma of the colon was also present. In the series .of Hauser,"" of carcinoma of the colon, five were associated witli more or less extensive " polyposis,"' and in the stomach the same author reports one case in which the process was combined. (Case 25, p. 208.)

One of the cases of bcnig-n tumor of the gastric mucosa which Sklifossowsky so positively ranks with the inflammatory hyperplasias, possessed at the same time a carcinomn, which was sufficiently interesting, on account of the early changes it showed, for Israel to report it under the title " Ueber die ersten Aufange des Magenkrebs." " Also, in the case of Petrow, of diffuse gastro-intestinal polypous hyperplasia, death took place from invagination aud spontaneous rupture at two places, where the growth had a similarity to adenocarcinoma.

To substantiate the view that the polypous growth occurs first and that the production of tumor follows, the following citations will suflHce:

Orth,"" in considering similar growths in the Fallopian tube, writes as follows: " Among the recently reported cases of papillary new growths are some which may be correctly deemed benign and others which are malignant; from the great similarity of these to one another it is safe to accept the view that there is at least a danger of cancerous transformation. Hauser, in the report mentioned of a case of Polyposis intestinalis adenomatosa, claims (p. 44G) that one must admit that the multiple warty growths have developed first and that these later underwent a carcinomatous change. CuUen,"^ after referring to the opinion of Lubarsch, that a benign tumor is never changed into a malignant one, says:

" Case 4.262, which I have recently had the opportunity of studying, shows beyond a doubt that such a possibility exists." The case in question was that of a polypous adenoma of the uterine mucosa.

The investigations on inflammatory hyperplasia with tumor-formation in certain regions have been repeated by Stoerk " in the urinary tract. He describes a case of papillomatosis of the urinary bladder, ureter and pelvis, of the right kidney, and was able to find only two similar cases in the literature. He considers the process as an unusual form of chronic inflammatory hyperplasia, and compares it with Gastritis proliferans. More commonly the chronic inflammation in the urinary passages terminates in a hyperplasia associated with the formation of cysts. That certain cases should display both features of the process is not sur


■» Das CylindiTepithel-carciuom des Magens und des Diclvdarms, p. 261, 1890, Jena.

"Berl. klin. Wchn?chr,, xxvii, p. 649, 1890.

"L. c, p. 539.

2' Cancer of the Uterus, etc., p. 3.55, 1900, N. T.

"Beit. z. path. Anat. u. z. allg. Path., xxvi, p. 367, 1899, .Jena.


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[No. 130.


prising. Litten "■"' has described " Ureteritis chronica cystica polyposa." Cahen "" has one case, and to this Stoerlv adds three more, in which the liyperphisia of the mucous lining of the bladder was accompanied by carcinoma. Kehn "' makes the interesting statement that in the majority of tumors of the bladder a substance in solution in the urine causes the tumor-growth by its chemical irritation; he has observed three cases in which tumors of the bladder occurred in men employed in the manufacture of aniline dyes. Stoerk is inclined to lay strong emphasis upon gonorrhoea as an etiological factor, and Kaufmann ^ has described the occurrence of multiple polypi in the ureter from the passage throiigh it of fitces from a fistulous connection between the pelvis of tlie kidney and the duodenum. As an example of the question which so constantly recurs — tumor or inflammation — and serving as an illustration of the apparent necessity to separate these conditions, the following quotation will answer:^ "The condition described might be classed both as chronic cystitis and as tumor. ... I am inclined to look upon the process as a chronic cystitis." This is in concluding an article on Cystitis Papillomatosa, where the cystoscopic examination left the observer in doubt. In the recent work by Mullen on Cancer of the Uterus, there is abundant evidence that a diffuse polypous hyperplasia of the uterine mucosa occurs and that this condition may be combined with carcinoma. The illustrations on pages 514 and 516 show its gross anatomy; some participation of the epithelium in the process is evident, since in many ]daces it was many layers in depth in both cases, notwithstanding that no karyokinetic figures were found. Case 3,453 (p. 333) of " adenocarcinoma of the anterior cervical lip ; commencing adenocarcinoma of the posterior lip, apparently independent of the former; papillary outgrowths of the uterine mucosa, with suspicion of commencing adenocarcinoma of the body of the uterus," is a striking analogy with the polypous hyperplasia with carcinomatous transformation observed in the intestinal mucosa and the urinary tract. Perhaps the best example of polypous hyperplasia described by Cullen is Case G,G59 (p. 401). Occurring in a young woman, aged 30, this author describes " a very unusual polypoid condition," in which " the mucosa, as a whole, presents a most unusual picture, consisting of large polyp-like masses springing from all parts and completely filling the enlarged cavity." Histolngioally, "one of the chief features is the preservation of the himiua of the glands; few, if any, nuclear figures are to be made out," and "the uterine muscle has not been penetrated by the growtli ; in fact, at some points there still remains a small amount of normal mucosa separating the growth from tlie muscle." There had been no reciirrence of tumor 11 months after the removal of the uterus. The diagnosis was adenocarcinoma. There is but little doubt,


« Arch. f. path. Anat. (etc.), Ixvi, p. 13!», ISTfi, Berl.

ssArch. f. path. Anat. (etc.), cxiii p. 468, tSSS, "Berl,

" Verhandl. d. deutsch. Gesellsrh, f. Chir., xxit, s. 340, ISfl.i, Berl.

«» Cited by Stoerk.

29 F. Bierhoff, The Medical News, Ixxvi, p. 810, 1!)00, I'hil.


SO far as one can judge from the report, that in this case the process was one of diffuse polypous hyperplasia which, so far as the examination shows, had not at the time of removal undergone carcinomatous change. That such a change would have occurred, had it been undisturbed, might be inferred from the continuity of process which has been shown so far to exist between the polypous hyperplasia and carcinoma.

But it is especially concerning tumors of the Fallopian tube that confusion has arisen; there has been quite a general failure to recognize that a diffuse hyperplastic inflammation is possible— a process which is strictly analogous to the polypous hyperplasia of other mucous surfaces — and that in certain typical examples it is as distinct from tumorgrowth as gastritis proliferans is from carcinoma of the stomach. Part of the confusion is no doubt due to the fact that hyperplasia is so frequently combined with sacto-salpinx. Slavyanski " has recognized this fact, as is established by the frequency with which he uses the term sactosalpinr papiUomatofta, although he does not clearly distinguish between papilloma as a tumor and polypous hyperplasia due to chronic inflammation. He states that " with occlusion of the abdominal end, the tube appears larger, aside from the papilloma; products of the secretion both from the covering of the tumor and the diseased mucosa accumulate in the tube: thus saeto-salpinx becomes sactosalpinx papillomatosa (p. 113)." Numerous investigations in lower animals have proven that when the outer end of the tube is closed a retention cyst is the result," Undoubtedly in many cases the inflammatory process which leads to the hyperplasia of the mucous lining of the tube causes the closure of the abdominal end. As a typical example, the case reported by Doleris and Macrcz "' will answer. He removed from a woman, aged 37, a growth of the right tube which was adherent to the liver and measured 30 by 30 cm. It consisted of a sac filled with grumous, viscid, yellowish fluid; its walls were 5 to 10 mm. and the lining was beset with pin-head to pea-sized papillary growths, which, on microscopic examination, consisted of villi with rarely more than one layer of epithelial cells as a covering. This is the second growth of this sort removed by Doleris; the other, in 1891," being the first observed in France. The woman was 28 years old; the growth was in the right tube and the inner one-fourth of the sacto-salpinx contained no jiapillary growths. Clark lias reported a similar case " of a cystic growth of the Fallo|iinn tube 13 liy 13 cm., or ono-hnlf tlie size of a man's bead, in which the inner surface was studded with thick papillary growths except at one point, where the


'"Special Pathology and Therapy of the Diseases of Women, vol. ii, Diseases of the Fallopian Tubes and Ovaries (Russian), 1807, St. Petersburg-.

" C. Gebhard : Patholoiiisclie Anatoniie der weiblichen Sexualorii'ane, pp. 436-7, 18(19, Leipzig; also: Ergebnisse d. allg. Path. u. ]iat'i. Anat., 1898, V, 741 (work of Sadkowsky), W'iesbaden.

Si La Gynecologie, iii, p. 389, 1898, Paris.

Nouv. Archiv. d'Obstet. et de Gynec, vi, p. 11, 1891, Paris.

s-" Johns Hopkins Hospital Bulletin, ix, p. 163, 1898.


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JOHNS HOPKINS HOSPITAL BULLETIN.


59


surface for au area the size of a palm was smooth. The wall of this cyst was thin; the warty growths were largely made ujj of connective tissue, and the epithelial covering of these was uniformly single-layered.' Although Clark ascribes the process to inflammation, it is reported as the seventh instance of papilloma of the Fallopian tuhe. Another instance first reported on account of the concurrent appendicitis ^ was shown on later examination of the sac," which was as large as a foetal head, to contain the inner part of the tube as"a curved cord on its outer surface. The lining of the sac was beset with small growths covered with epithelium; the crypts between the growths extended outward so as to give to the section an appearance not unlike an adenoma. The condition described in this case might be considered as analogous to cystitis cystica of Stoerk and others, which led Aschoff to search for glands in the urinary tracts of newly born infants. It is essentially the same process — a hyperplasia of the lining (sacto-salpinx villosa et pseudo-foUicularis). Both this case and that of Montprofit and Pillief" are included by Macrez in the table of benign papillary timiors of the tube; in concluding the case above mentioned, the following interesting statement is made:

" L'origine irritative de ces productions dans la trompe ne doit pas surprendre, puisque Ton voit que dans les visceres comme le foie, le rein, la capsule surrenale, etc., les formations adenomateuses coexistent avec la sclerose et paraissent etre un des modes de reaction des cellules parenchymateuses aux irritations qui amenent Tepaississement dii tissu conjonctive."

The second case of papilloma reported by Doran'" was double-sided; the right tube contained over a pint of fluid, the left a smaller amount. Both contained papillary growths wliich Doran describes as warts " similar in principle to those found in other structures, namely, overgrown papilla;, the result of continued irritation."

It is certainlj' of doubtful propriety to consider these growths, so clearly the products of an inflammatory action, as " papilloma." Sacto-salpinx papillomatosa might be altered with advantage to Sacto-salpinx polyposa, for the condition is one of diifuse polypous hyperplasia associated with the formation of a retention cyst and not one of tumorgrowth. By some observers the diffuse villous hyperplasia associated with sacto-salpinx has been reported as carcinoma. W. L. Jakobson '" has reported a case in which the papillary growths almost filled the sac. Although the epithelium had not proliferated so as to invade the musculature of the tube, and notwithstanding that there were no metastatic growths, the condition of the tube was diagnosed carcinoma by both Jakobson and' Petroff, who made the histological examination. In the case reported by Hofbauer '° both tubes were


35 Bull. Soc. Anat. de Par., 1897, xi, n. s., p. ."ilS.

^V. Macrez : Des Tumenrs papillaires de la Trompe deFallope, p. 61, 1899, Paris.

3' Bull. Soe. Anat. de Par., 1893, vii, p. .50.5.

38 Tr. Path. Soc, 1888, xxxlx, p. 300, London.

39 J. akush. 1 jensk. boliez., xii, p. 29, 1898, St. Petersb. "Arch. f. Gyniikol., Iv, p. ."JIB, 1898, Berl.


closed externally, but retention cysts were absent. The lining of the right tube, in which the changes were more advanced, possessed small miliary and larger growths, some as large as two beans. From the gross changes and from the careful description of the histologic structure, this might also be considered as polypous salpingitis, did not the record point so well to tuberculous salpingitis. The sac in the case operated by Leopold and described by Fearne " measured 5 cm. in diameter and occupied the infundibulum and ampulla of the tube. It was filled with a soft vascular papillary growth. Tlie lining folds have hypertrophied, branched, and then, according to Fearne, undergone malignant transformation. The muscle fibers had disappeared by atrophy and a firm connective-tissue wall had so successfully limited the process that there were no metastatic growths and the patient was well li years later." The case reported by Sanger and Earth," over which they hesitated long before concluding that it was one of carcinoma, which diagnosis has constituted one of the principal factors of the present confusion, was one in which the tubal mucosa was thickened so that it resembled the cerebral convolutions in miniature. The accompanying illustration, shov/ing the macroscopic appearance of the lining, resembles greatly the mammillated appearance of the stomach in gastritis proliferans. This thickening affected the outer one-half of the tube uniformly; there were numerous nuclear figures in the epithelial cells which covered the villi in a single layer, and largely from this histologic similarity with " Adenoma malignum " of Euge and Veit, these authors concluded finally that it also was carcinoma. The diffuse character of the process in this case, and the uniformity with which the tubal mucosa was involved, point to a hyperplasia similar to that seen in other mucous coats — to a condition resulting from inflammatory reaction with excessive proliferation or the early disappearance of all other changes but proliferation — a process which Adami, following Klebs, refers to as "neoplastic hyperplasia," and which Hauser, as before noted, connects with tumors by the term " polyposis adenomatosa."

It does not always happen that the outer end of the tube becomes closed by the inflammatory process; the subsequent invasion of the adjacent peritoneum, by papillary or warty growths, however, is no proof that the process is one of tumor-growth; for, in condyloma acuminata an exactly similar process occurs — extension of a hyperplastic inflammation by direct continuity of surface. The classical case of Doran " is of this nature. The outer part of the right tube was dilated and filled with cauliflower-like growths; these were formed by villi covered by a single layer of epithelium of which some colls were ciliated. There was also an enormous ascites and pleural effusions which required frequent


•"tTber primiire Tubcncarcinom. Geburtshiilfe u. Gynakologie, ii, p. .337, 1895, Leipzig.

«Tr. Obstet. Soc. (London), 1898, .xl, p. 303.

" Die Krankheiten der Eileiter, A. Martin, p. 353, 1895. Berl.

«Tr. Path. Soc. (London), 1880, xxxi, p. 174; Idem., 1883, xxxiii Supplementary Reports, p. 49.


60


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 120.


tapping; although it was impossible to remove the eutii-e growth, uo recurrence had taken place IG years after the operation.*' It is more reasonable to believe this case to be one of hyperplastic salpingitis than of tumor. Doran, in his original report, likened it to the venereal condylomas and to the indammatory polypi of the tubal mucosa described by Eokitansky and Hennig.

Another condition has been described by SchirschoS '" as papilloma. It is that of a single pedunculated tumor which arose from the lining of the tube 5 mm. inside the limbriaj; the abdominal os was wide and gaping. The growth was 5 em. in length and made up of a cluster of smaller masses. The exact pathologic position this growth should occupy as regards the Fallopian tube will always be in doubt, smce there is but slight mention of the large (wt. 410 g.) papillary cystoma which was situated just below the outer end of the tube. In other cases such localized growths have beeu catalogued as carcinoma. Stroganoif has described a single pedunculated growth which arose from the mucosa by a pedicle 1 em. in diameter. The tube containing it was closed externally and held about 50 ccm. of the usual serohemorrhagic fluid. The structure of this growth was such that a diagnosis was made of " carcinoma cylindro cellulare."" There is no mention of regional invasion, glandular involvement or recurrence; the woman was 39 years old. Tuffier" found in a tube, which was closed externally, pear-shaped and as large as a fretal head, a dark, soft and friable mass which was at first supposed to be free; in examining it a narrow pedicle was found. The lining of the sac containing this growth was, for the greater part, smooth and devoid of epithelium. The examination of this growth alone, which, like that of Strogonoff, was largely necrotic, led to a diagnosis of carcinoma (epithelioma).

Falk " also described a localized growth as carcinoma. On the left side the tube formed a sac that contained a sauious, semi-purulent fluid and in its outer part gelatinous cysts; the sac formed by the right tube was as large as a child's head. It contained a similar fluid, free, grayisli, villous masses, and on the posterior wall springing from the mucosa, a growth the size of a walnut; this contained gland-liko structures, and from its histologic resemblance to the case of Sanger and Barth, a diagnosis of carcinoma was reached. It is obvious that iii this instance the chronic inflammation on one side caused sacto-salpinx with hyperplasia of the lining and the formation of pseudocysts; on the opposite side, sacto-salpinx with the production of a localized growth. In eases of this nature, the effort to separate tumor and hyperplasia meets, in the localized nature of the growth, an obstacle which is at present insuperable. If there occur in


<5A System of Gynecology, by many writers, edited by T. C. Allbiitt and W. S. Playfair: Diseases of tbe Fallopian Tube by Alban Dorau, p. 806, 1897, London.

«Bolnitsch. gas. Botkina., Nos. 42-44, 1898.

■"Collection of works in Obstetrics and Gynecology, dedicated to Prof. K. F. Slavyanski (Russian), p. 227, 1894, St. Petersburg.

48 Ann. de Gyn^c. et d'Obst., 1894, xlii, p. 203, Paris.

"Berl. kliii. Wcbuseli., 1898, xxxv, p. 5.54.


such localized growths evidences of the multiplication of cells — nuclear figures — or if alterations are found in the morphology and staining reactions of the cells which would indicate that they have not reached an adult type, the process is certainly more like tumor thau like hyperplasia. But between hyperplasia and carcinoma there is a considerable gap. Hauser, after describing the multiplication of the glands in the polypi of the intestine, makes the statement "° tliat it should not be understood that all such growths are of necessity precursors of carcinoma. With the article of Schmieden theie are portrayed atypical karyokinetic figures in the liver cells which form the adenomata. In short, it seems to nie that the case described by Falk does not correspond to carcinoma so much as it does to a benign and localized growth; here it is necessary to recur to a proposition made earlier — that it is doubtful whether the narrow distance now separating hyperplasia from benign tumor will be increased. It is reasonable to believe that there should occur in the lining of the Fallopian tube regenerative processes, similar to those of glandular organs and structures possessing glands, the products of wliich are closely allied to adenomata.

The foregoing considerations demonstrate the imperceptible transition of hyperplastic processes of the tubal mucosa — belonging properly to the salpingitides — into those of true tumor growth; and that these may terminate in the production of benign tumors. The literature of tubal tumors also contains abundant evidence that the transition of villous hyperplasia into growths that at least possess some indications of malignancy is an equally gradual one. The tumors demonstrated by Kaltenbach as double-sided tubal carcinoma °" were later elaborately described as papillomata." Carcinoma is positively excluded in the following words: " Aber nirgends lasst sich doch ein Anhaltspunkt fiir eine wirkliehe Carcinombildung finden, audi da nicht, wo die Neubildung mehr einen parenchymatosen Character hat, und von einer Zerstorung des bindegewehigen Papillarkorpers durch eingedrungene Epithelmassen ist nichts zu sehen." Notwithstanding this statement, there was a recurrence within IS months.'* In Eckhardt's case the cyst formed by the dilated outer portion of the tube had small elevations on its external surface which, on microscopic examination, were found to consist of solid outgrowths of epithelium. In a report by Fabricius,'" the left tube was removed and the growth that it contained pronounced papilloma by Paltauf. The right adnexa appeared normal and were left in place. Five months later a large growth occupied the right side of the pelvis, and masses removed from where the left tube had been amputated were declared by Paltauf to be carci


5»L. c, p. 447.

51 L. 0.

5- Centralbl. f. Gynak., xvi, p. 357, 1889.

s'Ztsch. f. Geburtsh. u. Gyniik., 1889, xvi, p.

"Doran Tr. Obstet. Soc, 1898, xl, p. 200.

"•Arcliiv f. Gynak., 1897, liii, p. 183, Berl.

■«Wien. klin. Wcbnscb., 1899, xii, p. 1230.


564, Stuttg.


March, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


61


noma. lu the instance chronicled by MichnofE," the folds of the lining of the left tube were thickened by many strata of epithelium and the muscular layers in some places were invaded through their entire thickness. The condition in the right tube considered by Michnoff as papilloma corresponds very well with sacto-salpinx villosa; the epithelium, rarely more than a single layer, covered papillary growths 1 cm. tall, and these filled the canal near the outer end of the tube; the os abdoniinale was closed and a cyst had formed there the size of a small hen's egg. In a case reported by Krctz as papilloma," sacs had formed on both sides tliat exhibited externally small, white, soft, flat nodules. By the study of serial sections, these were found to be produced by the growth outward of the crypts between villi; the diverticula produced in this manner usually possessed a single layer of tall epithelium; where the epithelium was in two or three layers the cells were shorter and nuclei more spherical. Such cystic formations were found within the lymph channels.

Although it is not within the scope of this article to insist on the glandular character of the epithelial tubal tumors, certain facts may be pointed out. It is obvious that the five cases above cited as examples of growths that were removed during the transition between hyperplasia and tumor are very similar to proliferating papillary cystoma of the ovary. This similarity with ovarian tumors has been dwelt wpon by many writers. Gebhard'" compares them with uterine ■ carcinoma in the following words : " Obwohl ich selbst, wie eingangs erwiihnt, keine eigene Erfahrungen liber das Tubencarcinom besitze, so bin ich doch bei der Durchsicht der in der Litteratur niedergelegteu Beschreibungen des mikroskopischen Verhaltens dieser Geschwuslt zur iiberzeugung gekommen, dass dieselbe histologiseh durehaus mit dem malignen Adenom u. Adenocarcinom des Uteruskorpers auf eine Stufe zu stellen ist."

The classification of tubal careinomata into purely papillary and papillo-alveolar by Siinger and Barth °° is but a makeshift for adenocarcinoma; as Cullen says,"' concerning adenocarcinoma of the uterus, " I am strongly of the opinion that where the papillary arrangement is most marked, the growth has started in the surface epithelium; whereas it seems probable that when the gland-like arrangement is more pronounced, the process has started first in the glands. The simpler plan would be to consider all these merely as variations in one disease." Slavyanski "" would limit the term adenocarcinoma to the latter form of Sanger and Bartli. He separates them into two forms — carcinoma papillomatosa villosum and carcinoma C3lindrocellulare sen adenocarcinoma.

From the description of the following ease it may be seen that the view of Cullen relative to the two "methods of growth in tlie adenocarcinoma of jlic uterus is equally applicable to


"Meditsina, iii, p. 181, 1891, St. Petersb. "Wien. klin. Wohnsch., 1894, vii, p. 573. "L. c, ]i. 4.5.5.


fiO j^


r


«'L. c, p. 300. «5L. c, p. llfi.


tubal careinomata; that there is a disposition to grow towards the lumen in the form of branching villi as well as outward into tlie muscular coat as sacs, diverticula or alveoli, and that these methods of growth are part of the same process.°°

I received, June 22, 1899, from Dr. Henry P. Newman of Chicago, a tumor which was removed by him at the West Side Hospital. I am deeply indebted to him for the opportunity to examine it. The following abstract of the clinical history was also obtained from liim:

Mrs. F., age 47, admitted to the West Side Hospital June 20th; in her early married life she had two miscarriages at the third and fourth months of pregnancy respectively. Subsequently, she gave birth at term to a child, which is now 21 years of age; delivery was instrumental and severe. Since then she has been unable to carry a child beyond tlie third or fourth month of pregnancy. In spite of many miscarriages she has enjoyed a fair degree of health until two years ago, when menstruation became painful. The pain was referred to the sides and lower abdomen; it began just before the flow and continued during the entire period; there was also experienced general weakness and exhaustion on sliglit exertion. One year ago she first noticed a protrusion from the vagina which she took to be the womb; this has gradually enlarged, becoming more prominent after standing, straining, and coughing. It has never been painful, but has proved annoying in walking or sitting from its large size. There has also been an enlargement of the abdomen until it is now as large as a pregnancy at full term. She complains of a frontal headache; she has a fair digestion; there is no constipation or urinary trouble, but there is a constant leucorrhoea and the discharge is often streaked with blood.

Operation. — Incision in the median line of the abdomen 8 cm. long; over two gallons of ascitic fluid escaped; the left tube was very much enlarged and thickened; the ovary was not involved. The tube was excised close to the cornu of the uterus. Tlie right adnexa appeared normal; wound closed with catgut and silk in layers. The protruding culde-sac of Douglas was then opened from below, emptied of its contents— a large amount of ascitic fluid — and the vaginal fornix, which was so redundant as to protrude at the vulva, was removed and its edges closed with catgut sutures. The uterus was curetted and packed with iodoform gauze. There was nothing removed from the uterus which led to any suspicion of its containing a neoplasm. The patient, though fractious and unmanageable, made an uninterrupted recover)', leaving the hospital at the end of the third week.

Maceoscopical Appearance.

The mass consists simply of the left Fallopian tube. Its uterine end tapers abruptly and the abdominal end is the seat of an e\ul)(>ranf, eaulillower-like growth of new tissue which appears to have burst fdvlli fi-iiiii flio tul)e (Fig. 1).


«3Tlii3 case was briefly reported at the Cliieagi) Gynecoloijical Society, December 15, 1899, I)y Dr. Newmnii and myself.


62


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 120.


The tube forms a small U-shaped bend, the convexity of which is upward. The middle of this convolution measures 1.5 em. in diameter. It then bends downward and becomes greatly dilated. Its external surface is covered with a smooth, glistening, unbroken serous membrane which contains many circularly arranged blood-vessels. All signs of fimbrias at the outer end have disappeared. At the external end is an abrupt termination of the smooth serous covering which is overrun with tissue grown out of the abdominal ostium. This new tissue consists in part of small, smooth nodules which vary from .6 and .8 to 1,5 and 2 cm. in diameter and of shaggy, rough tissue between the rounded parts. This outgrowth is spread over more of the under surface of the tube than elsewhere; it is very friable. The ovary and its ligament form a pedunculated appendage to the tumor mass and is small as compared to the large tube (Fig. 2). The length of the growth is 13.5 em. The ovary contains a large corpus luteum; the external surface is smooth. Just in front of the tubo-ovarian ligament is a small accessory tube measuring 28 mm., springing directly from the serous covering of the main tube; its stalk is 1 mm. in diameter; its outer end is dilated (Fig. 1). The weight of the entire mass is 250 grammes. The tumor was hardened entire, and without cutting, in Mueller's fluid and formalin (4 per cent), except a small, irregular mass detached from the external end; this was hardened in strong alcohol (95 per cent). When the hardening was completed the tube was sectioned through its long axis. The center was found occupied by a soft material of a gray color; it filled the canal, and extends between the projecting masses of tissue which fringe the lining (Fig. 3). The muscular coats are thin, but the mucosa by its proliferation has invaded the necrotic eontent of the tube for a distance which averages 1 cm. in all parts of the tube. The proliferating lining is dotted over with grayish, necrotic debris. The greatest accumulation of this material has occurred in the middle of the tube where it measures 2 cm. in diameter; at this point the remaining 5 cm. of the diameter of the tube is occupied mainly by the proliferating mucous membrane. The muscular and fibroserous coats measure from 1 to 3 nun. in thickness. At the uterine end of the tube there is a large amount of necrotic material in the lumen and but slight proliferation of the lining; at the abdominal end this condition is reversed.

Microscopic Appeahance.

Sections were cut from points along the whole length of the tube and stained by various methods. The structure is essentially the same in all portions. Set upon the muscular coats, which are thin, are many papillary or villous growths. They are usually tenuous stalks of connective tissue covered with epithelium (Fig. 1), which branches and rebranches to form a tassellated lining (Fig. 4). The epithelium consists of many strata, of which only the deeper layers have a columnar type. The nuclei are oval and irregular and do not stain very strongly. The absence of a nuclear membrane and the arrangement of the chromatin in certain


nuclei betokens poorly preserved karyokinetic figures. This assumption is made certain by finding, after some search, certain masses of chromatin which are plate-shaped and, in other cells, the double plates of metakinesis. Such nuclei in process of division are quite numerous; they are as abundant in the outer strata as in the inner. In sections stained after the iron-hoematoxylin method, these nuclei in various stages of division form black masses. In some of the dividing nuclei, in spite of the unfavorable fixation, the centrosomes and the pointed ends of the groups of achromatic threads may be seen. There are no more irregularities in these dividing nuclei than might be accounted for by the hardening process. The layers of cells often number ten to twenty and in the outer parts of the tumor near the abdominal end they are even more numerous. The manylayered appearance of the epithelium is not due to the thickness or obliquity of the section, for in very thin sections cut in paraffin and not more than one cell in thickness, at least four to six layers are present, and this is true for regions where the outer layers have undergone considerable necrosis, where, in fact, the tips of papillffi are buried in necrotic debris. In no place are any single rows of epithelium upon a basement membrane found, such as occurs in the normal folds of the tubal mucosa. With low powers of the microscope the epithelial character of these cells is not clearly evident because of the large size of the nuclei as compared with the scanty amount of protoplasm surroimding them. Even with the immersion objective some appear to possess very little protoplasm. The nuclei alone average about seven mikrons in diameter when they are circular; the nuclei of the columnar cells measure in their long diameter ten to eleven mikrons. Exceptionally very large nuclei may be found which measure 15 to 20 mikrons in diameter. In practically every nucleus of the resting cells there may be found snuiU oval bodies colored a pale green, with the hsematoxylin and eosin staining; with the iron and luematoxylin and considerable differentiation, these bodies are much darker. Very rarely two occur in the same nucleus; they are undoubtedly nucleoli; the peculiarity consists in their large size. Very often they equal in diameter onethird or one-fourth of the diameter of the nucleus; exceptionally they occupy one-third of the entire nucleus. The columnar shape of the cells close to the stroma is manifested more by the shape of the nucleus than by the cell body; in this region the nuclei are more closely arranged in palisade form.

On the edges of these villous growths where the epithelium is in contact with the necrotic material, and in places where tlie edges of papillre are in contact, the epithelial cells have undergone degenerative changes. Here occur occasional nuclei, usually smaller, in which the chromatin is collected in a few granules which stain intensely with nuclear dyes, and such granules commonly festoon the inner margin of the nuclear membrane or form a few crescent-shaped masses on its lining. Such nuclei may appear devoid of cell bodies. More frequently the necrosis has resulted in shrunken and


THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH. 1901.


PLATE XV.



Fig. I. — Tubal carcinoma — anterior surface — natural size.

a. — Accessory tube.


Fig. 3. — Tubal carcinoma — posterior surface — natural size. (( Ovary.


Fig. S — Tubal carcinoma sectioned longitudinally (three-fourths of natural size).

(I. — Uterine end.

b. — Muscular wall.

c. — Necrotic tissue.

<l. — Papillary growth of the liiiiug toward tlie lumen of the tube.


THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH, 1901.


PLATE XVI.


fe.


^V


f



"mm


1




.mm -.■.-.saJrl*??'

W


■w ■"


C


■li;.'"



•/


- J.



Fig. i. — Villi that liave beeu seetionetl longitudinally and transversely; Irimi tlie more central part of the growth. II. — Necrotic tissue. h. — Connect ive- tissue stalk, f. — Ejiithelial cells in many strata.






■ _■ •%;.^v.>-.;, ...... ;,•


Fiu. 11. — "Invertintc tyi>e " of [uoliferation. The epithelium between the papillary growtlis has proliferated outward toward the muscular wall.

(/. — Necrotic tissue.

h. — Stroma.

<•. —Epithelium.

il. — Masses of epitlndinni linin;; cavities that have not been opened in this section.



- /


M



Fig. 5. — Intricate arranuemcnt of stroma and epitlielium in which il is ditlicuU to interpret the appearances without the study of serial sections.

n. — Necrotic tissue.

h. — Stroma.


Fig. 7. — Showini;' the outward urdwtli of intervillous ejiithe. Hum and the llattcnini;- of the thereby produced diverticula against the muscular wall of the tube.

!(.— Diverticulum lilled with necrotic tissue.

Ik — Beginning papillary ]troliferntion of eidthelinin into the diverticulum (cystl.

c. — Muscular wall of tube — only a jiart of wiiii-h is shown.


Makch, liioj.j


JOHNS HOPKINS HOSPITAL BULLETIN.


63


irrognlar miplri which stain deejjly throughout. Some luick'i also liave long, twisted and irroguhirly tortuoiTS extensions. I'pon tlie ultimate border occurs a zone eomjiosed ol' dust-like granules of chromatin. In the necrotic tissue in wliich the free ends of the papiUiB are embedded, tliere may l)e found occasionally cells distinguishable by their shape and size which have, however, lost all power to react to nuclear dyes; they assume the same tint with eosin as the granular nuiterial in which Ihey lie. Leucocytes arc present in the epithelial covering of the }iapilla\ but only as isolated cells; they are never accumulated in foci. Although often of the polymorphonuclear type, there arc also many with small round nuclei. In the layers of epithelium they are easily distinguished from the epithelial cells in process of division, but in the outer bordering zones of necrosis they lose their identity. The leucocytes are often present in the walls of the vessels of the stroma.

The stronui or connective-tissue stalks upon which the epithelium is arranged to form papillary growths is very delicate (Fig. 4). It consists of but little more than a vessel wall. On each side of the lumen of the'vessel are from three to six layers of parallel long cells which resemble the cells of involuntary muscle. Their nixclei are slender and from 20 to 30 mikrons in length and possess rounded or abruj)t, blunt ends. The margins of these cells are obscure when in contact; but in advantageous places it is possible to see that the c(dls, like the nuclei, are spindle-shaped. Where papillae have been cut across, the ends of the divided nuclei of these cells ajipear round and the nuclear membranes are much darker than when in longitudinal planes. Elastic fibers (Weigert's stain) are present neither in the walls of the blood-vessels of the connective-tissue stalks nor in the layers of cells which surround the vessels. The endothelial lining of the vessels is well preserved and shows no changes. 'J'here is some fibrin in some of the vessels and a snuill quantity in the necrotic tissue between the papilla\; in either case it never consists of more than a delicate network, extremely irregular. In sections from all parts of the tube examined it is possible to find villous outgrowths, the epithelium of which has become completely necrotic, but in which the stroma has not entirely lost its staining properties. Such papillse^ stained with Van Gieson's stain, show prolongations of the stroma extending f(n- even long distances into the necrotic material before their nuclei, too, suffer chromatolysis. In some papilhu the epithelium is entirely necrotic upon both sides for only a short segment of its extent, the fuchsin-stained stroma bridging over the defect.

It is evident from the foregoing description that the papillary growths in this tumor consist mainly of an epithelial covering of many layers and that the proliferation of these has been so marked that they have filled the tube entirely, distended it to a marked degree and have undergone a considerable necrosis. The necrotic tissue has filled the enlarged channel. These growths have been referred to as stalks, as villous growths; when cut directly across, their outline is circular. Such circular bodies lying in the midst


of the necrotic tissue have a striking appearance, since in certain sections they are found at considerable distances from any other tissue. Their outer margin is bordered by the dark circde of pycnotie nuclei and chromatin granules; the larger part of the body consists of the mass of epithelium with the radially disposed nuclei, and a small vessel containing numerous red blood-cells forms the center.

As might be expected, these villous growths have no regularity in their arrangement. The study of many sections cut in series shows that the entanglement is very intricate (Fig. 5). Arising from the wall of the tube, their course may be directly toward the lumen or oblique or even parallel to the wall. To complicate the arrangement, the villous growths frequently join one another as well as branch; consequently, in certain sections there may be seen at short distances from the muscular walls regions made up entirely of masses of epithelium, each mass consisting of a papilla cut obliquely or transversely, and containing in its center the blood-vessel. The edges of these clusters of epithelium may be in contact and the line of division difficult to find; in other places a narrow row of necrotic cells separates the epithelium of different papilhe; in yet other places the necrotic material has accumulated between them so that they appear well separated.

In deeper zones nep.rer the muscular walls still another peculiar appearance is obtained. Here the condition is reversed; the stroma l)ordcrs (he ei>ithelinni on the outside, and the epithelium lines a cavity filled with necrotic tissue (Fig. 6). The examination of serial sections shows that such cyst-like collections of cells are due to the growth outward, toward the muscular layers, of that part of the mucosa which intervenes between the villous prolongations; these outward growths, when cut across, appear like small cysts filled with necrotic tissue. As a rule the lining of these cavities at the inner margin is sharp and distinct. The layers of the epithelium are the same in character and number as those which cover the papillse. ]t is essentially the same epithelium; the proliferation toward the lumen has resulted in villous growths; toward the muscular wall, in cavities; and these, when sectioned, appear like cysts. The necrotic material which fills them usually stains lightly and with eosin, but some are nu't with which are quite filled with chromatin granules; such cysts (so-called for convenience) have a darkly stained content. Naturall}', such cavities are not always sectioned directly across; they often appear long and parallel to the muscular wall, or they are short and more oval. The muscular wall is bordered in this manner with but little interruption. It is obvious that the intei'papillary proliferation outward toward the muscular wall has met with an obstruction; the distention of the tube has not been able to keep pace with the proliferation of the epithelium. Sections occasionally show the following condition: the inner border of the muscular wall of the tube is covereil with the saiue epithelium in strata as has been described upon the papilhr. This epithelium lines a cavity the opposite wall of wliich is quite distant (the width of


64


JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. 120.


the field, Obj. 3, Ocular 3, Leitz) and from the opposite wall small villous growths project toward the muscular wall; the remainder of the cavity is filled with necrotic tissue (Fig. 7). These cystic formations in some sections, with the tissue in which they lie, form a zone of considerable width just inside the muscular coats.

The tissue between the cysts is made up of the .<ame elements as those described in the stroma of the villus, except that between the cysts it is abundant, whereas in the villi it is insignificant. It contains the long spindle cells, in all respects identical with those found in the villi; also many vessels in which are little more than loose-walled sinuses. Scattered leucocytes are seen frequently both with round and with irregular nuclei. The greater part of the stroma is apparently formed by fibers; some of them stain red with Van Gieson's stain; most do not. There are no elastic fibers among them. Numerous slender capillaries, which are so delicate that a single red corpuscle fills the lumen completely, are conspicuous in some sections in the stroma; with the iron-hajmatoxylin stain, by which the red blood-cells are made almost black, such capillaries, filled with blackened cells, form a distinct delicate network.

Very peculiar appearances are caused by the occurrence in the stroma, in certain places, of collections of bloodserum'" — oedematous regions. The coagulated senun usually has small holes in it, oval in shape, which resemble the holes in the cells of a fatty liver; often leucocytes are found in the holes. The margins of the serum are beset with semicircular spaces; both the oval holes and the marginal defects are due to tlie shrinkage of the coagulated serum. In such oedematous situations, and in the tissue of the bordering zones, are found large swollen cells in all stages of dropsical degeneration; the wall of the cell forms a bag for the network produced by the vacuoles. Such vacuoles do not have the clear outline of holes which at one time contained fat. Often considerable fibrin occurs in the oedematous spots, and in places oedema is combined with hicmorrhage. Plasma or mast cells are- not present in the oedematous districts or in the stroma elsewhere.

The question naturally presents itself: Are there any loose, unconnected, wandering epithelial cells in the stroma? A careful search for these was made in different ways. Many cysts were examined to see if at their outer margins there could be found any evidences of the proliferation of the epithelium outward into the stroma. Also many serial sections were examined to see if any of the collections of epitheliiim which form cysts were entirely unconnected and cut off; a third evidence of such a process was sought for, viz., cells in the stroma with nuclei in mitosis. All of these signs of invasion of the stroma by loose and wandering epithelial cells were absent. The proliferation of the epithelium has been c?i masse; by the proliferation of the tubal lining as a membrane; also by the production of a lining of many strata.


" The fluid of the blood is readily coagulated by burdening in solutions which contain chromic acid or its salts.


The muscular wall of the tube averages 1 to 2 mm. in width. The muscle fibers are few in number; sections stained by the fiicrofuchsiii mixture reveal a large amount of fibrous connective tissue which takes a brilliaut red color; this preponderance of fibrous tissue is especially marked in the inner half of tlie wall. The circular coat has undergone the greatest atrojjhy; only occasional strands of it arc present.

The outer half of the fibro-muscvilar wall is more loosely arranged. There are many large, flattened blood-vessels in this portion and around them small aggregations of fat. In the inner one-half of the wall occur occasional clusters of lymphoid cells that show the effects of pressure, being greatly elongated and parallel with the fibers. Such lymphoid nodes made up entirely of cells that correspond to small lymphocytes occur in all sections. In a few sections there arc islands of cells that present a different appearance; closely aggregated cells with pale nuclei form an elliptical clump that possesses a very definite margin. Careful examination fails to reveal any nuclear figures in these cells; their nuclei possess very little chromatin; their arrangement is quite irregular; for these reasons and the fact that no lining cells can be found for the spaces in which they lie, a conclusion was reached that these islands have resulted from the proliferation of the endothelial lining of lymph channels. Still other islands of cells leave no doubt but that the proliferating ejiitheliiiii! has penetrated deeply within the fibro-muscular wall. In a few. sections, lying nearer the inner border of tliis wall, are irregular tubules lined with epithelial cells. The nuclei of the cells are long, occupy most of the cell and stain deeply. The cells are columnar and in places two or three strata in depth. Some of these tubules occur within lymph channels, for outside the deeper and more columnar cells the endothelial lining of the channel is easily recognizable. Since these deeper prolongations of the epithelium were found so seldom, no effort was made to prove their connection by serial sections with the more centrally located parts of the tumor. The ovary contained no tumor tissue.

From Dr. W. W. Sheppard, the family physician, it was learned that for some time after the operation the patient was " nervous and hysterical," but improvement was steady and she was soon able to be up and around the house a part of each day. About nine or ten weeks after the operation ascites reappeared and upon vaginal examination a tumor, the size of an orange, was found on the left side. The ascites was relieved by tapping two or three times, the first being done on November 1st. During the month of December Dr. Byron Eobinson was called in consultation. He has informed me that he found the abdomen enormously distended by a large tumor and considerable ascitic fiuid. The patient was sitting up and able to walk about the house; her general appearance was cachectic, pulse 120, temperature 100'^ F. Tlie tumor arose from tlic small pelvis and upon vaginal exaniiiiation was found to be fixed, except its uppermost portion, which was slightly movable. It was


March, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


65


located chiefly on the left side. The uterus was slightly enlarged.

Operation (by Dr. Eobinson). — Upon opening the abdominal cavity with a long median incision the entire peritoneum was found studded with paiiillomatous growths which varied in size from those barely visible to some as large as a hen's egg. The larger ones were located in the lower, left quadrant of the cavity, and in this jjosition were adherent to one another so as to form an irregular mass. There were approximately two gallons of a clear ascitic fluid, similar in tint to pale ale, in the cavity. The irregular tumor on the left side was firmly adherent to the left lateral wall of the small pelvis; it extended ujiward so as to be in front of the sigmoid; the omentum was firmly adherent to it, and in the omentum near the tumor and also in the adjacent mesentery were many small shot-sized and pea-sized warty growths. Most of these growths had a pale yellowish color a,nd were like a fresh brain in consistency; some of the smaller growths appeared very vascular. All of the larger growths were removed.

Eecovery followed the second operation without any special events. At present she is able to perform some of her customary household duties. The ascites returned gradually so that about five months after the second operation paracentesis was necessary for the patient's comfort; and it has been practiced every two or throe weeks since. At one time eleven quarts were removed, at another twelve quarts; the fluid maintains its former characteristics. A sample of this fluid showed on examination the following features: sp. gr. 1007, alkaline reaction, a large amount of albumin, absence of sugar, a moderate amount of proteids (biuret reaction), absence of bile, and .3 of 1 per cent of urea. I received the tumor masses removed by Dr. Eobinson after they had been in a weak aqueous solution (1 per cent) of formalin for several days.

Macroscopic. — They consist of three large masses and about a dozen smaller; altogether they weigh 1,3.j0' grammes. The largest piece measures 16 X 13.5 X 4 cm. and is disk-shaped; on section it presents a granular surface which resembles somewhat adipose tissue. Its external surface is smooth except for tag-like, torn adhesions. Its concave side has a furrowed and trabeculated appearance. The next smaller in size is very irregular in form, measuring 12 X 10 X 5 cm.; it is very rough and nodular externally and in spots has been torn. The smallest of the large pieces measures 11 X 7.5 X-l.S cm., and on section is found to possess a much softened, necrotic center. One of its flat surfaces is quite smooth. All of the smaller masses are very irregular; some appear to be little more than fibrous tissue, others resemble the larger masses.

Microscopic (continued). — Sections were made of all the large growths, and some of the smaller, and stained by various methods. A large part of all the growths consists of necrotic tissue ; many sections contain little else. The necrosis is most marked in and around the central portions; svich necrotic tissue stains lightly or darkly according to the


degree of chromatolysis; varying degrees of oedema and quantities of fibrin occur as well as small hisemorrhages. In sections where necrosis is less marked, the appearance of the innermost parts of the tubal tumor are duplicated; here occur cross-sections of papillaj lying in the necrotic tissue which are in all respects similar to those in the tube in size, shape, paucity of stroma and number of epithelial strata ; the cpitlielial cells contain similar large nucleoli. Xaryokinetic figures, however, are much more numerous; often three, four or six dividing nuclei are present in a single field of the immersion objective (celloidin sections, 15 to 20 mikrons thick). The stroma of the papillae —connectivetissue stalks — has its origin in a capsule which surrounds each metastatic growth more or less completely. Tlie capsule is formed by long cells arranged parallel to the circumference whose oblong nuclei contain nucleoli which are barely visible; these cells are not arranged in layers, for the nuclei have been cut in all possible diameters; the cells resemble the " fibroblasts " of organizing granidation tissue. In sections of the various metastatic growths, and even in different sections of the same growth, the capsule shows large blood-vessels, regions of necrosis and of ha?morrhage and thrombosed vessels. In regions just internal to the capsule, where the papillomatous growths have been so luxuriant that the papillaa are in contact and a tissue has been produced which appears solid and granular, if the stroma be examined in such places the conneclive-tissue cells arc also found with mitotic figures. They are never as abundant as the dividing nuclei of the epithelium; that the stroma or supporting tissue contains cells which are multiplying is be3'ond doubt; that these cells are the same as those which constitute the stroma is also certain, since all stages of multiplication by indirect division may be found and also for the reason that there are no other cells in the stroma with resting nuclei than those described. It may be inferred that this difference between the stroma of the papillae in tlie primary tumor and that in the papillaj of the metastatic growths is due to more favorable conditions of nutrition; it is also possible that the more rapid proliferation of the epithelium, as is shown by the abundance of dividing nuclei, has in itself led to a proliferation of the cells of the framework, and that tin's has been sufficient in amount to allow the observation of occasional dividing nuclei in the stroma cells.

This condition of embryonal stroma and embryonal epithelium, since both contain dividing nuclei, has resulted in a line of demarcation where epithelium and connective tissue meet, which is much less distinct than similar lines of contact in the primary tumor. In regions close to the capsule, where there has been a rich growth of papillse and necrosis has not occurred, the indistinct line of contact and the entanglement of pajiilln? renders it difficult to distinguish between epithelium and connective tissue. Some aid may be had fniin tlic coliiniiiar po-^ition of the nuclei of the epithelium on the stronui, but this does not always obtain; in other places the epithelium has contracted away from


m


JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. l-M.


the stroma so that a narrow siaace is present. The bloodvessels in the stroma have very little wall; they resemble the vessels comniojily eneountered in a small spindle-eelled sarcoma.

Among tile tumors of the FnUopian tube that can be considered as careinomata, this case is uni(|ue in the following particulars: The os abdominale was evidently open, since there was not formed the usual sac, and invasion of the peritoneal surface and adjacent tissues probably took ])lace via this opening by continuity of surface. The case is also remarkable in that large secondary tumor masses were removed from the abdominal cavity, the patient still living, although slowly sui'cumliing to the disease."' The similarity


' The patient died Feljniary IS, lilOt ; tlirousli tlu- Ivindness of Dr. Sheppard, a uecropsy was secured, tlie details of wliicli will be shortly published.


in method of growth and general histologic structure to proliferating cystadeiiomata of the ovary is continued in the comparative benignancy of the peritoneal metastases.

The appended table comprises 21 eases of carcinoma that were selected from .j2 cases that have been reported as [lapilloma or carcinoma. 15 of the 52 were excluded by reasmi of insultieient data; of the remaining 37 some have been ^hown to be instances of hyperplasia of the tubal mucosa due to inllammation, a process usually combined with sacto-salpinx, that leads to the formation of benign localized growths whose position in the domain of tumors is very questionaljle, or to more diffuse growths that may possess some of the characteristics of malignancy; the latter resemble the careinomata that develop in scars, burns or fistuhT' from


long-continued irritation.


AUTHOR, TITLE AND PT.ACE OF PUBLICATION.


E. SeniJrcr: llebcr eiii primiiros Sarkom dur Tuben. Centralbl.l. Gvnak., ]88ti, X, p. 601, Leipzig.

E. G. DrUimann : Ueber Cai-ciiioina Tubie. Ztsch. f. (ichurtsh. u. Gyniik., 1 88, XV, p. 312, Stuttg.


A. Doran: Primary Cancer of the Fallopian Tube. Tr. Path. Soc. (Lonciojii,

1888, XXXIX, p. 2IH.

C. J. Eborth and H. Kaltenbach : '/aiv PathoIog:ie der 'rubon. Ztsch. f. Gcburtsh. II. Gvniik.,

1889, XVI, p.' 3.17, Stuttg.

T. Landan and ,1. Kheinstein; Reitrilge znrpatholoprischrn Anatoniip der 'rul)e. Archi\-f. Gyniik., 1890-lU. XXXIX,p.273, licrl.

S. D. Michnoff: A Case of Primary Carcinoma of the Fallopian Tubes (ttussian). Moditsina, 1891, III. p. ]81, St. Petersb.

P. Zweifel : Vorlesungen iiber klinischc Gynak., ]8»;;, p. 13il, Herlin.


F. .T. E. Wp.sterniark and U. Quesnel : Ett fall af dubbelsiiiig kancer i tubip Fallopii. Nord. Med. Ark., 1893. XXIV, Nr. 2, p. 1. .Stockholm.


UILATERAI. OK UNILATERAL.


liilatcral.


Kight tube.


Kight tube.


Hilateral.


Kight tube.


left tube.


Biliteral.


Jiilateral.


CONDITION

OF THE

OPPOSITE TUBE.


Pyosalpin.x.


Left tube at operation appeared small.


Outer end closed and a sac f*u*mcd that containeii .500 ccm. of bloody, thin fluid.


Sacto-sali)inx paplUomatosa.


CLOSURE OF OS

ABDOMINALE

AND FORMATION

OF A SAC.


In both tubes there occurred two dilatations or sacs.


The outer I'Hil, greatiN ■liiatpd opi'iiiil inio an al)sci'ss ca\ ity.


Outer end closed ; a sac formed.


L.— dilated to size

of thumb. It.— large I (faustgn'issc.l


Sac fornicfl on right side.


Left tube formed a sac as large as a large list.


Large sacs on both silk's. L. tube 20 (in. lone and 8 cm, I hick.


Sacs formed on both sideslarger on left.


KECUHHKNCE

OR RECOVERY.

DEATH SOON

AFTER OPERATION.


Tumor found at necroi)sy.


I>eath on sixth day after oper; tiou.


Recurrence: li\'ed nearly eleven months after ope ration.


Recurred in 18 months.


Recurred in 10 months.


Iteeui'rence in 7 months.


PresumaVily recurrence, since patient died l>i years after operation.

Recurrence: death in ti\'e months.


CONCERNING METASTASIS, INVASION OF ABSCESS CAVITIES, ETC.


In Douglas's pouch a small growth.


The tuuKtr had in\aded two alisccssca\'ities.

A small nodule in the "exca\atio vesico-uterina.

A swollen l.\iuph gland in the small pelvis.


Lumbar glands inxaded.


.^ubjieritonca! nodules noted on the right tube.


.\scites after the operation, with hard masses in the^abdoraen.


A cyst occurred at .iunction of right tube and o\'ary, size of a hen's egg: it was tilled with clear tiuid.


In\asi(m of cyst

<if right ovary. No exudate in

peritoneal

cavity at

necropsy. Lymph glands of

small pelvis in \aded. T.— no.lulcsfiiund

in the li\ er at

the necropsy.


CONDITION

OF THE

OVARIFS.


Uoth normal.


vVbscesscs in botl o\'aries.


U.— cancerous.


Normal.


L.— ovary left in Ijody, it was iml)cddeil in adhesions.

R.— normal.


Normal.


L.— ovary cystic. Jlonolocular cyst size of an orange.


REMARKS.


Reported as sarcoma.


.\t necropsy, tumor found in the uterine vesical and \aginal mucosa.

Demonstrated tirst as carcdnoma.

lfepi>rtcd later as paidlloma.


Carcinoma of the cervix found at the necropsy.


March, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


67


AUTHOR, TITLE AND PLACE OF


BILATERAL OR


CONDITION OF THE


CLOSURE OF OS AUDOMINALE


RECURRENCE OB RECOVERY.


CONCERNING METASTASIS, INVASION OF


CONDITION OF THE


RK.MARKS.


PUBLICATION.


l-NILATERAL.


OPPOSITE TUBE.


AND FORMATION OF A SAC.


DE.\TH SOON AFTER OPERATION.


ABSCESS CAVITIES, ETC.


OVARIES.



H. Kretz : Zur Casu

nilateral.



L,— tube 17 cm.



Small subperito

Unknown.


Reported as


istic der Papillome




long and 6 to 8



neal nodules



papitloinata.


lier Eileiter. Wien.




cm. in diameter.



noted, exter


K i-etz considers


klin. Wfhnsch., 1S94,




R.— tube similar.



nally on both



the case similar


VII, p. .57L'.




Both closed e.vterually.



tubes. Invasion of the l.vraph channels, (histohigic examination).



to that of Eberth and Kaltenbach.


W. Fisehel : Ueber


Bilateral (?)


Condition of left


R.-tuhe formed


Recurrence :


Small nodules on


L'nknown.


Part of the cyst


eiiif'Ti Fall von pri


tube not posi

a sac 8by 4..5cni.


death se\en


external surfai-e



of the right tube


iniirem papilliiri'iii



ti\ely known.



months after


of riKht tube.



possessed a


Krel:)S der Muttur


It was imbedded



the operation.


Abdominal ca\lty



smooth wall


ti-ompeten. Lapa


in adhesions and




contained clear



ccjvered by a


rotomie, Heilung,



not removed.




ascitic fluid.



single layer of


Ztseh. f. Heilk., ksas,








short epithe

XVI, p. H3.








hum.


A. Uosthoin : Pii

Right tube.


At necropsy left


Sac ftu'med by


Recurrence :


Inguinal glands


Cyst of right


Necropsy by


m*ires medullai-es



tube found to


right tube sup

death si.x


removed at a


ovary.


Chiari.


Cat-einoma tiilur.



contain meta

posed to be


months after


second oper



Ztsfh. f. Heilk,, 1S!W,



static iVt tumor


pyosalpin.x.


first operation.


ation. Retro



XVII, p. ITT.



nodules.




Iieritoneal glands found iinaded at the necropsy.




T. ,T. Watkiiis(aii«l E.


nilateral.



Both tubes large


Recurrence :


Ext. end of the


L.— ovary many


Ci)ndition of right


Hi^s' : Exhibitiuii ol




and formed bj'


death seven


right tube con

corpora candi

o\'ar.\' not clear.


unique iiiieroseopie




fourconv(du

months later.


nected to a mass


cantia.



sections of papilloma




tions; both



4x4x5cm. This




and carcinoma of




closed e.\ tern


contains a cen



the tubes, etc. Am.




ally.



tral cavity beset




CJyn. and Obst. J.,






with sc\'eral




liitfT, XI, p. 273, N. Y.






wart\' growths. Metastatic carcinomata on the ovaries and on post, surface of right tube. Collections of luiniir
















cells found in









h'mi»h channels









of wall of left









tube.




E. Falk: Fortschritte


Left tube.


I'nknown.


Left tube closed


Recurrence :



L.— ovary normal.


Tumor found in


u. jfe^enwiirtifi-rr




externally. Sac


death seven




the uterus in


Stand der \ ayinalcn




formed.


months after




mucosa n4-ar


Operations terlinik.





operation.




right ostium


Tlierap. Monatsh.,








and diagnosed


18i»7, XI, p. ai:j, Uerl.








as sarcoma \vas siipp(iscd to be respotisilile for recurrence and death.


K. Eckardt: Eln Fall


Left tube.


Normal. (Doran*.


Sac formed by


Healthy a few


Subperitoneal


Both normal.


Broad ligament


von primiirem Tnb



the left tube


months later.


elevations, size



shortened by


encarcinom. Arcli.




size of child's


Subsequent


of hazel-nut.



invasion of the


t. Cvnak., 1897, LI II,




head.


history un

make external



tumor.


p. 18:1.





known.


surface irregular.




A. H. PiUiet: Epithe

Hi-ht tube.


CrdiUown.


Ca\ity in the


History not


Invasion of the


Condition of left



lioma de la tronipe




right tube oi)po

known.


lymjih channels.


ovary unknown.



uterine. Bull. .Soc.




site o\ary.



(histologic ex

R.— in\aded by



Anat. de Par., 18117,






amination.)


tumor in its



XI, p. 956.







(juter part only.



C. H. Roberts : A Case


lUsjht tube.


•■ The loft tube


Outer end of


Well ten months



Normal.


\'ery brief histo

of Primary Carci


inflamed and


right tutie


later.




logic descriiJtion.


noma of the Falloi>


closed."


closed : sac





ian tube. Tr. Obst.




formed.






Soc. London, 1898,









XL, p 189.









J. Fabricius: lieitriiK-e


Left tube.


At first operation


Supposed to be a


Recurrence 11 \e



Llnknown.


At the first oper

zur Casiiistik der



the right adne.xa


p.vosalpinx until


months later




ation masses removed were


Tubemarrinoiiu'


appeared n<)r

it was cut.


when a large




Wien. kliii.Wiliiisrli.



inal : at second.



mass tilled the




in-onounced


1899. XII, IJ. \-£U.



thickened.



right half of the pelvis.




papilloma. At thi- second (qicration when radical rcini>val was found to be inipossiljle, masses were removed that were pronounced carcinoma.


68


JOHNS HOPKINS HOSPITAL BULLETIN.


[No. 120.


AUTHOR. TITLE AND PLACE OF PUBLICATION.


BILATEB.iL OH UNILATERAL.


CONDITION

OF THE

OPPOSITE TUBE.


CLOSURE OF OS

ABDOMINALE

AND FORM.^TION

OF A SAO.


REOtlRRENOE

OR RECOVERY.

DEATH SOON

AFTER OPERATION.


CONCERNING METASTASIS, INVASION OF ABSCESS CAVITIES, ETC.


CONDITION OF THE OVARIES.


REMARKS.


J. Fabricius: Idem.


Right tube.


L.—adoexa ap

Abdominal open

Recurrence: five


Carcinomatous


Right ovary en

After second




peared normal


ins leads into a


months after


invasion of the


larged but


oi>eratinii a




at the opera

cyst.


first operation


cyst on right


otherwise


lartre cyst de



tion.



left adnexa and uterus were removed.


side. At the second operation it was found that the entire peritoneum was beset with small tumor nodules. The metastatic nodules on the outer surface of the uterus were examined and pronounced adenocarcinoma.


normal.


veloped that reached upward to the na\'el and finally evacuated through the rectum.


Danel : Essai sur les


Left tube.


Appeared healthy


Left tube formed


Recurrence took


Many peritoneal




Tumcurs malif^iios



at operation.


a sac.


place on the


gro^vths on the




primiti\('S (U- la Tronipe rterine,



Not removed.



right side.


uterine end of the tube.




1S9«, i*aris.






Enlarged glands in the adhesions around left tube.

Tumor cells found in the lymph cliannels. (Histologic examination.)




B. Friedenhelm: Beitrag zur Lehre \-om Tubencarcinom. Ueber ein primiires, rein alveoliires Carcinom der Tubenwand. Berl.


Left tube.


Unknown.


No sac formed.


History subse

Left tube and


L.— smooth ex

Tumor said to





quent to oper

tumor adherent


ternally, size of


have had its





ation unknown.


to colon.


a walnut, con

origin in an






Left parametrium inHltrated with tumor masses.


tained small cysts.


accessory tube.


klin. Wchnsch., 1899.









XXXVl, p. 542.









E. Mercclis: Primaiy carcinoma ot the Falloitian tube. N. Y. Med. J., 19UU, LXXII. p. 45.


Right tube.


Left tube re

Right tube 4 cm.


Recurrence on


Outer end of


L.— ovaiT small




moved. Con

in greate.>it


right side 18


right o\ary in

and firm— not




dition not


diameter.


months later.


vaded by tumor.


rt'moved.




described.


Outer end closed.




R., the seat of chronic inter








stitial changes.



REPORT UPON A CASE OF GONORRH(EAL ENDOCARDITIS IN A PATIENT DYING IN THE PUERPERIUM; WITH REFERENCE TO TWO RECENT SUSPECTED CASES.

By Norman MacLeod Harris, M. B., Associate in Bacteriology, Johns Hopkins University.

AND

William M. Dabney, M. D., Late Bcsiihnt Ohstelrician, Johns Hopkins Hospital.


Case 1. — I. T., aged 19, unmarried, was admitted to tlie Obstetrical Department of the Johns Hopkins Hospital on February 13, 1900, complaining of fever and wealvuess which she thought were of puerperal origin.

Family History. — Negative as far as could be ascertained.

Personal History. — There is no history of the ordinary diseases of childhood, nor of any acute infectious disease. She has never had rheumatism, and states that previous to the onset of the present illness she has always been a healthy woman.

Marital and Menstrual History. — Tlie patient is unmarried, and has had no previous children or miscarriages. The menstrual history is normal in all respects.

Present Ulness. — The patient states that she was confined


on January 19, 1900, after a hard but non-instrumental labor at term. (Child living.) During the course of the labor frequent vaginal examinations without aseptic or antiseptic precautions were made by those in attendance, and the third stage of labor was furthermore complicated by a retained placenta, which, after several attempts was removed manually, likewise without precautions. On the fourth day of the puerperium she was seized with a chill, followed by fever, and, later, sweating, and these symptoms have recurred regularly every day since then. Other symptoms have been headache and general pain in the limbs, nausea and vomiting, tlie latter at times marked, and almost complete loss of appetite. For the past few days .'jhe has had, in addition, a rather constant cough, accompanied by some pain in the


March, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


69


side. The patient says she has been confined to bed practically ever since labor, and, though she has felt at times better than at first, she has grown progressively weaker.

Physical Examination. — The patient's mental condition is very dull apparently, answering questions poorly, and only when repeated and asked in a loud voice. Well-formed and well-nourished woman, marked ana?mia present, the lips and mucous membranes being almost bloodless. Temperature on admission 102.4° F., pulse 120.

Thorax. — Well formed. Respirations rather hurried, with an occasional short, sharp cough.

Lungs. — Expans-ion fair, equal on the two sides. Vocal fremitus normal. Percussion note normal throughout. On auscultation at the base of each lung, a few very fine crackles are heard on deep inspiration, and here and there over both lungs an occasional medium moist rale. The breath-sounds are normal.

Heart. — The point of maximum impulse is neither visible nor palpable. No thrill or shock on palpation. Apparently no increase in the area of cardiac dvilness. On auscultation at the apex both sounds are practically obliterated by a to and fro murmur, the systolic being the louder and more intense. Both murmurs are transmitted and well heard in the axilla. Preceding the systolic murmur a rather loud rumble is heard at the apex, which is likewise transmitted to the axilla. Over the body of the heart both murmurs are well heard. Over the base the systolic murmur becomes diminished in intensit}', tlic diastolic more clear-cut and marked. The presystolic rumble is lost. The pulse is markedly collapsing in character, and there is a distinct capillary pulse present.

Abdomen. — Looks normal. No rose-spots are visible. There is no distension and the abdomen is everywhere soft on palpation.

Spleen. — Not palpable.

Liver. — No apparent increase in dulnoss. The edge is just palpable at the costal margin.

On palpation no mass can be felt in tiie pelvis on either side or in either iliac fossa.

Legs. — Q<]dematous and slightly swollen. No swelling or other changes in the joints noted.

Following admission on the morning of February 13th, the patient had several vomiting spells, attended by signs and symptoms of collapse, her skin becoming cold and clammy, and her pulse dropping from 120 to 80-90 to the minute, with an occasional intermission. When first seen in the afternoon, several hours after admission, the patient looked septic, but seemed to be in fair general condition. Temperature at this time was 101.6° F., pulse 113 to the minute, rather weak and of poor volume and tension. When seen again about 7.30 P. M., she was found to be in far better general condition, though markedly drowsy. Her history was taken at this time, and the physical examination made. A provisional diagnosis of ulcerative endocarditis of the aortic valve, secondary to puerperal infection, of probably strep


tococcic origin, was made at this time. During the night the temperature again rose, reaching its maximum, 103° F., about midnight, pulse 120 to the minute and much weaker. The general condition became very much worse, there being marked prostration with drenching sweats as a particularly noticeable feature. About 8.30 A. M., February 13th, the temperature had fallen to 100.8° F., the pulse, 80 to 90 to the minute, and of poor volume and tension. Attacks of vomiting, attended by increasing signs of collapse, continued, and the general condition seemed very much worse than at a corresponding time last night. Material for taking a culture from the uterus was secured about 9 A. M., a fair amount of bloody lochia being obtained.

The perineum was found practically intact. On vaginal examination the uterus was found enlarged, apparently normally involuted, according to the history, and slightly retroposed. The cervix was slightly torn. The adnexa seemed normal.

About an hour and a half later, the condition remaining about the same in the meanwhile, the patient had another very severe attack of vomiting, with great collapse and much sweating, so that, in spite of stimulation and subcutaneous infusion of normal salt solution, the pulse, which had fallen to 60 to the minute and was very weak and intermittent, gradually became weaker and finally ceased at the wrist, the patient djdng shortly thereafter.

Blood. — An examination of a fresh blood specimen was made about 9.30 A. M., February 13th, and found negative for malarial organisms. Apparently a leucocytosis was present.

Urine. — Examination of a specimen obtained during the night showed a distinct whitish flocculent precipitate, a distinct trace of albumin, no sugar, and no diazo-reaction. Microscopically a number of hyaline and some epithelial and pus casts, a number of pus cells and some ejjithelial cells, and a number of micro-organisms, some of which showed motility, were found.

Uterine Culture. — Cover-glass specimens, stained with gentian-violet, showed a few epithelial and some pus-cells, and possibly an occasional coccus or in doubtful pairs, but so few in number that it was impossible to say whether they decolorized by Gram's method or not. Cultures taken on bouillon, agar plates (2 dilutions), and anaerobic glucose agar, all remained sterile.

The history pointing so clearly to puerperal infection, the possibility of the gonorrhceal nature of the trouble was not thought of, and, in consequence, no attempt was made to obtain the gonococcus culturally from the uterus.

Patholociical Report.

Autopsy No. 1487, February 14th, 7.45 P. M., by Dr. W. G. MacCallum.

Anatomical Diagnosis. — Acute vegetative and iilcerative endocarditis, involving aortic, tricuspid and pulmonary artery valves. Acute splenic tumor. Infarction of spleen. Catarrhal cystitis. Puerperal uterus.


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[No. 120.


The l)otly is that of a young, wt'll-nourislied woman, whose hreasts arc in tlie puerperal state.

Upon section, the peritoneal cavity is i'ound to contain very little fluid, and the serous membrane is smooth and glistening.

The pelvic cavity contains a small amount of a brownish, slightly turbid fluid.

The omentum is bound down between the liver and spleen by fresh adhesions over a small area.

The pericardium, upon being opened, contains a small amount of feebly turbid fluid, Init its serous surfaces are smooth and glossy.

The Heart. — Weight 325 grams. The epicardium is smooth. The right auricle is normal. The foramen ovale is open to the extent of 3 mm. The ductus Botalli persists as a cord.

The tricuspid calve is delicate. Upon the posterior leaf, alnitting upon tlio septum ventriculorum, is a large lobulated vegetation which begins at the base of the valve and extends to its edge, hanging into the intervalvular space on the auricular surface of the valve. A granular mass also exists behind the valve, between it and the septum and lying upon the latter. Tlie leaflet lying to the left of this as the heart is opened, shows a few minute pin-point translucent elevations on its auricular surface. The larger lobulated vegetations arc ojjnciue and yellowish and surmounted by soft post-mortem clots.

The pulmonary artery valves- are delicate. At the junction of the right and left leaflets are small translucent vegetations on the ventricular surface.

The left aui-icle is normal.

The mitral valve is normal.

The aortic valves ure most extensively involved, the posterior segment alone being free from vegetations. The loft segment is surmounted on the ventricular side by a large mass of lobulated vegetations which extend down on to the ventricular wall. There is considerable roughening of tlie endocardium of the ventricle below the right segment also. The inner surfaces of these two segments in tlio sinuses of Valsalva are roughened and covered by soft dark-colored ])ost-mortem clots. From the right sinus of Valsalva a probe can be passed through an opening in the septum ventriculorum into the vegetations on the ventricular side in the right ventricle Ijeliind the tricuspid valve. This o])ening has probably been caused by an extension of the iiillammation through the septum.

The heart muscle is rather soft and brown in color.

Measurements: Circumference of tricuspid valve, 12 cm.; right ventricle, 8..5 X i cm.; circumference of mitral valve, 8 cm.; left ventricle, 7.5 X 12 cm.; circumference of aortic valve, 7.5 cm.

The lunys present a moderate degree of (cdema; otlierwisc they appear normal.

Spleen. Weight 300 grams. Measures 18 X 8 X G cm.

Excepting over two areas, one on the anterior surface


where the organ touches the liver, and the other at the posterior edge, the spleen is quite smooth. Corresponding to those areas of roughness the spleen is indurated and elevated. The anterior area is adherent to the liver by fresh adhesions, whilst over the posterior area are found a few fibrous adhesions only.

On section, these elevated firm areas are found to present the features of typical anajmic infarcts and are wedgeshaped. The spleen is soft and light purple in color. The great increase in bulk being in white spleen pulp. The Malpighian bodies are greatly enlarged and jirominent, with irregular margin.s, measuring 3 mm. in diameter. The splenic Jiulp proper is not very greatly increased, but seems very soft and siicculent.

The Liver. — AVeight 1000 grams. Surfaces are quite smooth excepting where tlie organ is adherent to tlie spleen.

Gall-bladder and ducts are normal.

On section, it is soft and flabby and greasy to the touch. The lobules are quite definitely marked out; the centers being translucent, beyond them comes a congested zone, then outside of it is a zone of pallor and yellow opacity.

The Kidneys. — Each w'eighs 175 grams, and in all respects are alike apparently. They are slightly larger than normal, and the capsules strip off readily. The stellate veins are markedly injected, and between them the parenchyma has a grayish look.

On section, the cortex is thickened and measures from 5-8 mm. The striations are fairly well marked. The glomeruli are visible, but there is, however, some opacity and an appearance of being much swollen in the labyrinthine portion. The lines and dots of yellow opaque material are quite noticeable. The pelves contain a thick ycllowisli fluid, but they are not, however, especially injected.

The ureters are apparently normal.

The urinary Madder contains a small quantity of thick, yellowish purifnrm fluid, and the mucosa is in places deeply injected.

The iilcrus is enlarged and soft. The mucosa is somewliat congested, but there is no sign of intlaniuiation (measurements of organ not given).

Fallopian tubes and ovaries are normal.

Ljanphatic glands are nowhere especially enlarged.

The lone-marroir (femur) is somewhat reddened.

Other organs and tissues appear normal.

MlCliOSCOrifAL EXAMIN-ATIOX OF TISSUES.

Heart muscle shows oedema and fragmentation (?).

Ltings also show general a'dema, leucocytosis in blood of all vessels, and some local atelectasis.

Mammary //lands show evidences of lieing in the nornuil state of lactation.

Spleen shows a slate of general enlargement. The ]iortion containing llie infai'dion cmild not be found, li.ning been inadvertently mislaid.

Liver presents evidences of chronic passive congestion with fatty metamorphosis.


March, 1901.]


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I


Kidneys. A laodcrato degi'eu of parenchymatous nephritis is noted, accompanied by a few foci of small roiiud cells, which also occur in the walls of the larger arteries.

Intestines exhibit simply post-mortem degeneration, and evidences of leucoeytosis in their blood-vessels.

Fallopian Tiibes. Mucosa normal; blood-vessels give evidence of a leucoeytosis.

Ulerus. Sections were cut from three sites: —

(a) Cervix (including part of vaginal portion).

(&) Body (], about the middle; 2, at the fundus).

These were stained in haimatoxylin and eosin, methylene blue, by Weigert's and by Gram's methods.

(a) Cervix, on being stained in hematoxylin and eosin, presented the following features: The vaginal portion gave evidence of post-mortem degeneration only; likewise in the lower part of the canal similar changes are found, and dense masses of material staining blue in the haematoxylin can be made out readily in small clefts in the disintegrated tissue, being in all jDrobability bacteria.

The mucosa of the upper portion of the canal shows no evidence of post-mortem change; it appears quite ragged and adhering to it in places are masses of what seem to be broken down red blood-corpuscles.

The submucosa is much richer in small round cells than is normal, and scattered about in moderate numbers are phagocytic cells containing altered blood jjigment. In places where evidences of mucous glands exist, it is found that they are choked with shed epithelium, at times retaining its columnar form and at otliers being changed into granular detritus staining well in eosin and showing much nuclear debris.

Throughout the remainder of the section is noted a more or less well developed degree of ccdema, best marked towards the parts beneath the mucosa. This oedematous fliiid contains large numbers of small round cells, a few plasma cells, and moderate numbers of large mono- and polymorphonuclear cells which frequently are seen loaded with altered blood pigment, few in number and located deeph^ in the lower portion of the section, but higher up much more numerous and approach the mucosa, wJiere they may be found lying in close contact to the deposits of Ijroken down red blood-corpuscles.

The blood-vessels everywhere are greatly dilated and show evidence of marked leucoeytosis, in which the polymorphonuclear cell prevails, but both large and small mononuclear cells are by no means scarce.

The arteries show no signs of either peri- or eudarleritis, but in some instances their walls are thickened, due to hypertrophy of the muscular coat. Amongst the larger arteries can be seen at times small, irregular areas of a hyaline nature which slain Ijrightly with eosin. The vasa vasorum give no evidence of inflammation.

The veins, especially along the course of the smaller ones, show at their peripheries considerable small, round-cell accompaniment.


Stained with methylene blue, the section presents no definite signs of the existence of micro-organisms. Notable, however, is the presence of numerous mast-zellen, more numerous in the deeper portions of the section than in the superficial parts.

Gram's stain, with Bismarck brown as counter-stain, simply brings out the presence of mast-zellen even more sharply than with methylene blue, but presents no signs of bacteria.

Weigert's stain shows no bacteria to be present.

(&) Body of Uterus. — Stained in hsmatoxylin and eosin.

Mucosa much thinner than normal. Xo columnar epithelium found. Xo jjlacental tissue was noted. A few mucous glands could be identified and were found filled with shed columnar epithelium, mucus and some small round cells.

The general condition is similar to that described under cervix section, but, if anything, the small round cell infiltration is more intense, esjiecially between the muscle-bundles.

The arteries show the same hyaline masses and there is no inflammation of the vasa vasorum. Occasionally seen in section from fundus, but more noticeably in the section from the middle portion of uterus, is a great thickening of the adventitious coat of the larger arteries and so dense that in places it resembles old dense hyalinized fibrous tissue. In these arteries the lumina can scarcely be traced and, in fact, a few show no lumina whatever, and their general coiirse is a very tortuous one.

Sections stained in methylene blue. Gram's or Weigert's stains, show no evidence of bacteria, but as before in cervical sections, show jircsence of mast-zellen whose granules at first glance might be mistaken for cocci.

Coverslip preparations were made from

(a) the valvular vegetations,

(b) the pericardial fluid,

(c) the splenic infarct,

(d) the pelvis of left kidney,

(c) the contents of the urinary bladder.

Xegative findings were recorded for (c), (c) and (d). Slips from the vegetations showed the presence of large nmubers of cocci, occurring singly, in pairs, in fours and in clusters; also, in numerous proportion, the various kinds of leucocytes, the polymorphonuclear ty])e greatly preponderating. The cocci for the most part appeared lying free, but not infrequently they occurred within cells. Tyjiical biscuit-shaped organisms were by no means the rule. They readily decolorized by Grani's method of staining.

The preparations from the urinary l)ladder exhibited several varieties of bacilli and cocci, but of the latter none could


be said to resemble the gonoeoccus.


Cidtures. — Unavoidable necessity delayed the use of special media for fifteen hours, but cultures in )ilain agar wei'e made at once from

(a and /;) Aortic ami tricuspid vegetations.

(c) Splenic infarct.

(d) Heart's blood. (c) Left kidney.


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[No. 130.


(f) Urinary bladder.

These cultures were poured into Petri dishes and incubated at 36.5° C. for 48 hours and then examined.

Results on plain agar:

(a) Aortic vegetations yielded the gonococcus, Streptococcus pyogenes, Bacillus coli communis.

The isolation of the gonococcus on the plain agar was due to its having developed ia a small fragment of blood-clot which had been carried over in making the culture. It was positively identified as such by its inability to grow on plain agar or ox-blood serum, but growing luxuriantly upon hydrocele fluid agar, and finally by decolorizing in Gram's stain.

(&) Tricuspid vegetation gave the above organisms with the exception of the gonococcus.

(c) Splenic infarct remained sterile.

(d) Heart's blood gave bacillus.

(e) Kidney was grossly contaminated by bac. subtilis.

(/) Urinary bladder yielded the Streptococcus pyogenes, Bacillus coli communis.

Cultures in hydrocele fluid agar were made from

(a) and (b) Vegetations on aortic and tricuspid valves.

((') Splenic infarct.

These were incubated for 48 hours at 3G.5° C. and then examined.

Three types of colonies were found, resembling those of B. coli communis, Streptococcus pyogenes and gonococcus. Transfers were made at once of the two former organisms to plain agar-slants, and of the latter to hydrocele fluid agar and plain agar-slants. Tj-pical growths of the colon-like bacillus and of the streptococcus were obtained on the plain agar^ and upon the hydrocele fluid agar isolated colonies identical with those of gonococcus grew out. Strange to relate, of flfteen plain agar-slants inoculated as checks from the suspected gonococcus colonies, two showed slight but definite growth of a scarcely perceptible nature, which, upon examination, yielded a diplococcus identical in morpliology and tinctorial reaction with the gonococcus. These two growths were transferred again to plain agar and also to h3'drocele fluid agar with the result that upon the latter medium only did development occur, and further attempts failed to produce growth from tliese liydrocele fluid cultures upon plain agar.

This .eame result Dr. Young states has at rare intervals come under liis notice also in tlie work of the genito-urinary clinic.

That the third typo of organism isolated from these plates was the gonococcus is proven by its failure to grow upon plain agar (excepting tlie two instances noted beforehand) and upon ox-blood scrum and other ordinary media, by its being able to grow upon media containing human blood (as noted on the plain agar plate) or human serum when grown at 37° C, and by its inability to retain the stain when treated by Gram's method.

Case 2.— Medical No. 9374. W. A., a^t. 28.

Was admitted to Ward F on November 25, 1898, beincr


sent in as a supposed case of typhoid fever. Patient complained of pains in the stomach, heart and kidneys.

Family history was of no importance.

Past History. — As a child he had measles and possibly typhoid fever. At 22 years of age he had an indefinite illness which was treated as smallpox, typhoid fever and diphtheria, during the course of which there occurred a swelling below the right ear which, on being opened, discharged pus. There is an indefinite history of malaria following three weeks after the above illness, which was cured by quinine.

Patient never had any urinary disturbances nor pains in lumbar region. He had gonorrhoea three years ago, accompanied by an inguinal bubo which did not suppurate; there were no other sequelae.

The patient denied syphilis; he was a moderate drinker.

Present illness began on September 2Gth. He partially recovered, but soon got worse again. He first noticed a general weakness, and had " dumb chills " for three weeks daily, followed by moderate sweats; there was neither nausea, nor vomiting, nor herpes, nor diarrhcea. He then got steadily worse and was confined to bed for 4-5 weeks. Improvement followed so that he got out of bed and staid in his room one week, then went about the house, but four days later he had a relapse, which, the patient thinks, turned into typhoid fever. This happened about a month ago; since then he was in bed until two weeks ago, when he got up and walked around, but owing to swelling of his legs and consequent stifl'ncss, he returned to bed. In this period he had herpes and night-sweats, although during the last three weeks the latter have been absent; likewise he experienced for the first time palpitation of the heart and shortness of breath, accompanied by a rather bad cough, worse at night. The expectoration is of a whitish color. Paroxysms of coughing at times caused vomiting, chiefly at night and very early in tlie morning.

The anlema of the logs has lasted two weeks and is no worse than when it began upon ilie third day of this relapse.

Bowels are irregular, and there is some increased frequency of micturition, especially at night.

Upon the day of admission (November 25th) he had chilly sensations and his temperature rose to ]01.8°, falling to 97° at 8 A. ir. on tlie 2Gth.

The ifliysical examination showed that patient was ana'uiic, and a pufFy condition of eyelids was noticeable. The pulse was of good volume but irregular in force and rliytlim. with a suggestion of a collapsing quality. Rate 26 to quarter minute. The heart was found to be enlarged, the point of maximum impulse being in the fifth interspace, 8.5 cut. from mid-sternal line. A thrill was felt.

Upon auscultation, at the base of lieart a short systolic murmur was noted, traceable to the anterior axillary line. Over body of heart a faint diastolic murmur was heard, becoming louder upon passing upwards and inwards. A friction rub was heard at the left of sternum in the second and third interspaces, and in the same situation to tlie right of sternum. At the aortic area a systolic murmur was quite


March, 1901.]


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73


readily heard. Over the pulmouic area the heart-sounds had a loud rumbling quality and the second sound was markedly accentuated and reduplicated. The lungs showed the presence of a few moist rales at the bases. The presence of fluid in the abdominal cavity was made out. ffidema was marked in the feet and legs. There was no general glandular enlargement.

Upon the 30th he seemed more comfortable, but the cardiac conditions became more pronounced and the lungs presented evidence of congestion. And upon the morning ol December 1st he was cyanotic and drowsy and had an annoying cough. The heart and lungs presented nothing new. ffidema was most noticeable in the tissues of face. Less urine was voided. At 8 P. M. he said he felt comfortable, but at 9.15 the nurse found him dead.

His blood was examined on day of admission and showed htemoglobiu 18 per cent, leucocytes 8600, red blood-corpuscles 1,768,000. On the 28th of November the leucocytes rose to 14,000, but upon the following day had fallen to 8000, whilst htemoglobin rose to 31 per cent.

Examination of the urine on the day of admission presented the following condition: S. G. 1.013; reaction acid; much albumin present; sugar absent; many epithelial casts, pus-cells and small, round, nucleated cells present; a few red blood-cells noticed. Diazo-reaction absent. Albumin was present until the day of patient's death and was estimated upon several occasions to vary from .8-1.3 per cent.

Abstract from the Pathological Eeport.

Anatomical Diagnosis. — Acute ulcerative endocarditis of pulmonary valve; ascites; hydrothorax and hydropericardium; acute splenic timior; small area of bronchopneumonia; glonierulo-nephritis; simple goiter; Meckel's diverticulum.

Autopsy by Dr. MacCallum, December 3, 1898. No. 1208. There was extensive oedema of the face, upper and lower extremities. The peritoneal cavity contained 600 cc. of slightly turbid lluid. Both pleural cavities contained excess of fluid.

The pericardial cavity contained about 200 cc. of a clear fluid in which floated a few flakes of coagulated lymph. Excepting over the right auricle, the serosa was smooth and glossy, here it was noticeably lustreless.

Heart. — Weight 400 grams. The right auricle and ventricle contain firm post-mortem clot. The tricuspid valves are delicate and competent. The pulmonary valves are the seat of a most extensive ulcerative endocarditis, two of its segments being almost completely destroyed, only tags witli friable vegetations remaining; the third segment is better preserved and carries on its free margin a soft, friable, rather granular mass measuring 1 X 2J cm. x\ortic and mitral valves normal.

Spleen weighs 800 grams and measures 23 X 13 X G cm. The organ is greatly enlarged and is attached by a few fresh slender adhesions to the body wall and stomach. Capsule generally thickened, but to a moderate degree only. Upon section the spleen is quite soft; color is dark purplish-red;


the trabeculae are well marked, and the ilalpighian bodies are readily visible.

The kidneys are both alike. They are enlarged, weighing together 470 grams and measuring 12| X 7 X -i^ cm. They are engorged with blood, oedematous and show all the typical signs of acute parenchymatous nephritis.

Bone-marrow of a femur is dark purple-red in color, soft but not difiiuent.

Tlie thyroid gland shows a moderate degree of goiter.

Lymph-glands generally are enlarged and firm.

The other organs are either normal or have no bearing in their pathological phenomena upon the special phase of disease under discussion.

Microscopic Examination.

Pulmonary Artery Valve. — One of the masses of vegetations examined shows that in its deeper parts it has been quite completely organized, but in its more superficial parts can be observed the presence of a dense mass of hyaline fibrin with a capping of more delicately fibrillated fibrin; more superficially are found small numbers of leucocytes.

The base of the valve is somewhat infiltrated.

Spleen shows great congestion. There is no evident increase in the other tissues. There is no especial accumulation of pigment.

Kidney section presents a few islands of connective tissue of small extent in the cortex. There are accumulations of small round cells about the blood-vessels and adjacent tubules. The tubules are dilated, the epithelium is degenerated and hyaline casts are numerous; many tubules" contain leucocytes which sometimes invade the casts. The glomeruli are enlarged and completely fill the capsular space, and show a marked increase in the cells contained within the capillaries, and in some instances a fibrous thickening of the capillary walls is observable.

Bone marrow presents an increase of lymphoid cells. There is no fatty tissue evident.

Lymph-glands show an increase of polymorphonuclear leucocytes and an increase of the endothelium of the sinuses, with swelling of these cells.

Bacteriological Eeport.

At the time of autopsy cultures were made in plain agar, as it was only upon the following day tliat a suspicion arose of the possibility of gonorrhoeal infection and no hydrocele fluid cultures were made. Tliis latter procedure was, however, resorted to later.

The cultures from the vegetations and other sources proved negative on plain agar, excepting those from the lung and peritoneal cavity, which yielded respectively the Streptococcus pyogenes and the Staph3'lococcus pyogenes albus.

Within 24 hours of the autopsy cultures were made from the vegetations upon the valve in ascitic fluid agar, but upon examination those proved to be unfit for working out on account of contamination.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Xo. 120.


Coverslip preparations were made and examined from the vegetations and from the nrethra. The former exhibited nnmerous diplocoeci sometimes within cells or amongst cell remains, but more often free. Their morphology corresponded closel_y to that of the gonococcus and they decolorized in Gram's solution. The latter preparation presented no definite micrococci.

Case 3.— Medical No. 9645. J. H. (colored), a^t. 22, was admitted to the hospital npon March 9, 1899, complaining of ])aiii and swelling in the right ankle.

Family history was negative.

ra»t Iliglorij. — In childhood he had lia<l uuunps, measles and whooping-cough. He never had had rheumatism, typhoid fever, diphtheria nor scarlet fever. He had pneumonia about four years ago. He has no urinary disturbances, and denies gonorrhcea and syphilis, but admits exposure to both.

He does not use alcohol or tobacco.

Present Illness. — One evening four weeks ago he complained of soreness in the right ankle and next morning noticed the region much swollen. Following this he had for several nights chilly sensations and fever accompanied by herpes labialis, but with no night-sweats. He was treated outside for rhemnatism.

At the present he complains of aching in all bis limbs and especially of pain in the right ankle, which causes him to turn in bed with much difficulty. His ankle joint is swollen.

Phi/sical Examination. — Patient looks ill. There is no cyanosis or herpes. Pressvire over femoral artery gave a decided Corrigan impulse, and upon auscultation it gave a pistol-shot sound.

The heart was found much enlarged, the point of maximum impulse being in the fifth interspace 9 cm. from mid-sternal line. There was no thrill present.

Upon auscultation at apex, a loud systolic murmur, traceable far out into the axilla, was heard; likewise a soft blowing diastolic murmur. These could l)e traced readily upwards and inwards, and could lie heard at the aortic and pulmonic areas and along both sternal borders. The second pulmonic sound was relatively accentuated. Pulse shows a fair volume and tension, collapses; rhythm regular and is 2G to the quarter minute.

Liing showed ]iresence of a few coarse nlles.

Abdomen and organs negative.

No general glandular enlargement.

Genitalia negative.

Legs show no oedema, no nodes, no scars.

]i'ii/hl initlc is a little swollen, sensitive to pressure, shows no efl'usion into joint.

Marcli Ifith, at midnight, vomiting set in ami patient comjilaiiK'd of al)dominal pain. Pulse small, feeble and rapid. At 8 A. ]\r. his temperature, previously nornnil, was found to be ]00.8'\ and the general condition improved considerably over what it had been during the night. But at S.^5 he died suddenly.


Blood E.raiii illation. — Leucocytes 55,000 upon day of admission.

Urine. — S. G. 1.011. H showed a few granular casts, epithelial cells and detritus; otherwise it was negative.

Medical bacteriological report upon ilarch 9th proved that the blood culture made was sterile.

Abstract from Pathological Eeport.

Autopsy by Dr. Flexner, ]\Iarch 11, 1899. No. 1306.

Anatomical Diaynosis. — Acute endocarditis, perforation of aortic and mitral valves; purulent myocarditis; purulent and liEemorrhagic pericarditis; chronic passive congestion of the lungs; acute splenic tumor; anaemic infarction of spleen and kidneys; acute nephritis; cloudy swelling of viscera.

No oedema present.

Area of jJcricardium uncovered by lung tissue measures 10 X 10 cm. Upon opening the pericardial sac there is an accumulation of hauuorrhagic and purulent fluid about the great vessels at the base of the heart in the dependent portions of the sac dorsally. In all about 20 cm. of bloody fluid, containing many floating grayish-white purulent nnisses, can be obtained. The pericardial sac is adherent to the pleural surface of the left lung. The visceral layer of the pericardium is injected ; the surface opaque, and there are yellowish adherent masses of fibrin and pus.

Heart weighs 400 grams.

The right and left auricles contain partially decolorized post-mortem clot. The tricuspid and pulmonary artery valves are apparently normal. The heart-wall is lax and the fibers well separated, and the myocardium of left ventricle shows pronounced fatty changes.

The aortic orifice above the valves measures 6 cm.

The Aortic Valve. — The right and middle segments of the valve appear delicate, and the left segment is neither retracted nor thickened, but has been perforated, apparently from below, in that there is a communication just above the base of the valve occupying the width of the right hemisphere of the segment, and measuring about 3 mm. Through this perforation there projects into the sinus of Valsalva a mingled red and white clot, tlie red poi'tion being soft, the white dense and opafjne. This clot almost fills the sinus and connects with a thruinlius located npon and within the acu'tic segment of the mitral valve. This latter thrombus is situated upon the attached jiortion of the mitral valve, chietly along the upper half. The valve has suffered a perforation at its base, so that the thrombus protrudes into the cavity of the left auricle. The endocardium of the left auricle above the valve bulges into the auricular cavity over an area 4 cm. sq., its elevation being 2-3 mm. There is no perceptible change in the endocardium itself. Upon incision of this diseased area one enters into a cavity in the substance of the heart-wall, which communicates with the thrombus covering the aortic and mitral valves. This valve [cavity?] contains necrotic and hiPmorrhagic material, and at the left edge there is a distinct collection of pus. The cavity meas


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ures 2i cm. in length nnd 1 c-ni. in depth: its walls are infiltrated and firm.

The spleen is enlarged and weiglis -lOO grams. It has no adhesions. Capsule delieate. In the mid-part of the ventrienlar .surface is a pinkish infarction measuring 2 X li "-'ii'- "'• section, the organ show.s great increase ol' sjilenic pulp, consistence is somewhat reduced and the ilal])ighian corpuscles are visible. The infarction, upon cutting into it, is found to extend inwards for 1^ cm. into tlu' splenic tissue; its consistence is firm.

The liver is congested and cloudy.

Ki(Iiicj/s. — The left one Is large. The capsule strips olf easily. There is a single anaemic infarction about i cm. in diameter, and lies quite superficially. Upon section the cortex is swollen and opaque; the glomeruli are visible and pink in color; striw are coarse. Thickness of cortex is 8 mm. Eesistance is lessened and the organ is oedematous and presents small hemorrhages in the pelvic mucosa. The right organ is the same in all respects as the left, except for a larger ana?mic infarction, measuring 10 X 12 mm., and a smaller one about the size of a hemp-seed. There are several punctate luvmorrhages in the kidney substance. Combined weight of kidneys is 400 grams.

The Riglit AnMe-joint. — The periarticular tiss\ies are apparently normal, and the joint contains no excess of fluid. and the synovial membrane is perfectly smooth.

The remaining organs present nothing of significance.

^IlCEOSCOI'ICAL Exam 1 NATION.

Tlii' lirarl-ijiiiscle is edematous.

The e])icardiuni is likewise cedematous and thickened, showing an extensive proliferation of blood-vessels constituting a granulation tissue. Upon the surface of this tissue are some remains of epithelium, and here and there a thin, fibrinous deposit. Another section taken through the area of suppuration contains a fibrinous coagulum with many fragments of nuclei; underlying this is a loose granulation tissue infiltrated with leucocytes.

(No sections were made through either of the affected valves, as the heart was jireserved as a museum specimen.)

Spleen. — The organ is . gorged with blood which spreads apart the splenic elements. One end of the section shows an area of necrosis of splenic tissue sharjjly marked off by a zone of hajmorrhage with a fibrinous network, inside which is a bluish zone of fragmented nuclei of leucocytes.

Kidney. — Cells of tubules are disintegrated and ragged, showing no nuclei. Some tubules are ]>acki'd with such desquamated cells.

The glomeruli show no extensive changes. There is no increase of interstitial tissue anywhere.

There are extensive accumulations of polymorphonuclear leucocytes found chiefly in the interstitial tissue, but often, too, in the tubules. Occasional small masses of plasma and round cells are seen in the medullary portions.

There is congestion of the capillary vessels.


Bacteriological Eepoet.

Kecogniziug the possible gouorrha-al origin of the heart lesion, cultures were made upon what at the time was thought to be human serum, as well as upon plain agar, from the vegetations and infarcted areas of s^jleeu and kidney. All endeavors to isolate the gonocoeeus failed, and this may be ex})lained l)y the later discovery that by inadvertence ox-blood serum had been used instead of human serum. From the agar-plates the following organisms were isolated :

((/) Streptocucciis pyogenes from vegetations on aortic and mitral valves, sinus of Valsalva, lung and renal infarct.

(b) Staphylococcus pyogenes aureus from vegetations on aortic valve, sinus of Valsalva and lung.

(f) Bae. proteus vulgaris from vegetations on mitral valve and sinus of Valsalva.

Cultures from heart's blood, liver, spleen, right ankle-joint and pericardium proved sterile.

Coverslips were from the vegetations on aortic and mitral valves, pericardial fluid, right ankle-joint, infarctions in spleen and kidney. Examination showed that in the vegetations there could be seen large numbers of large diplococci with some single or tetrad forms situated chiefly outside of leucocytes, only scattered polymorphonuclear leucocytes were found containing diplococci or groups of diplococci. The organisms readily decolorized by Gram's method of staining.

The pericardial fluid demonstrated the presence of vast numbers of polymorphonuclear, lesser numbers of large mononuclear and a few small mononuclear leucocytes, amongst which, after very careful searching, could be found a few polymorphonuclear cells containing small groups of diplococci within their protoplasm. These diplococci were larger than ordinary pus cocci, were biscuit-shaped and decolorized by Gram's method. Other coverslip preparations proved negative.

With these statements prescnteil, it is clearly proven that the flrst case is one of undouljted gonorrhceal origin. But it must be conceded that in the two latter cases the lack of clinical evidence of a recent gonorrhoea, and the failure to demonstrate the presence of gonococci in culture rather weakens the assumption of their being gonococcal in nature.

Yet from the demonstration on coverslip preparations from the material of the valvular vegetations of micrococci, coinciding in all respective non-cultural characteristics with those of standard descriptions of the gonocoeeus, and, from the peculiar massive formation of the vegetations themselves, we regard it as reasonable that both cases should, without much doubt, be considered as examples of gonorrhceal endocarditis.

Discussion.

A review of the literature since the publieation of Thayer & Lazear'.s article (.Journal of Experimental Jledioine, .Timnary, 1SS)0) shows the following' cases:

Scars (Medical & Surgical IJeports, Boston City Hosi^ital) reports a case in which, following several attacks of gonor


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[No. 1-20.


rhoea, the last attack five months before, the patient, a man aged 23, began to complain of pain in the back, stomach, and limbs, which gradually became more severe. The temperature was elevated from 99.5° F. to 105° F. Examination disclosed a harsh systolic murmur over the pericardium. As the disease progressed, the spleen became enlarged, and finally the pulse irregular and weak with marked cyanosis present. Death occurred on the seventh day after admission to the hospital. Autopsy showed an ulcerative mitral endocarditis, with rupture of the valve segments, infarcts in the left ventricle, spleen and kidneys, and on bacteriological examination a coccus was found quite generally distributed and unlike (he ordinary pus cocci. No cultures were taken.

Sears also states that of a hundred and sixty-seven cases of gonorrhoeal rheumatism admitted to the Boston City Hospital between the years 1880 and 1897, twenty-five showed cardiac murmurs to which no cause other than gonorrho-a was assignable.

Harhitz (Deutsch. med. Wochenschrift, 1899, XXV, pp. 131-134), in a study of forty-three cases of infectious (i. e. caused by organisms, streptococci, gonococci, etc.) endocarditis, found two in which organisms decolorizing by Gram's method, resembling gonococci in other respects, and not growing on the ordinary media (agar, serum, bouillon, gelatin), were found on the affected valves.

Jaccoiid, in a clinical lecture on gonorrhccal endocarditis (Journal de Medecine Intern., Paris, 1900, IV, pp. 513, etc.), mentions seventeen cases of gonorrhoeal endocarditis, his own and those he has collected for two years, in which the diagnosis was confirmed at autopsy. In four of these gonococci were found on coverslips from the valves, and in the remainder the history pointed clearly to it and autopsj' showed ulcerative endocarditis, though no mention is made of what was found bacteriologically. In one of these oases gonococci were found on the valves, and, moreover, the mjocardium was altered.

Karageos(/aiiz (Eshenedelnik, 1899, No. 46) reports the case of a man, aged 34, who when first seen complained of epididj'mitis and fever. Examination showed elevation of temperature, anaemia, and a marked systolic murmur over the pericardium. The heart was not enlarged. The spleen was enlarged, and, towards the end of the disease, was four fingers' breadth below the costal margin. The temperature was remittent in character, and there were chills and sweats. The patient had had no disease previously, except intermittent fever. Two years before he contracted gonorrhoea which had never been thoroughly cured, and occasionally showed exacerbations. Death occurred after an illness of one month. Autopsy showed friable yellowish vegetations of the aortic valve, with destruction of the valve segments. No bacteriological examination was made.

Berg (Medical Record, April, 1899) reports the case of a man who, after an attack of gonorrhcea, had involvement of the metacarpo-phalangeal joint of the left thumb, accompanied by chills and elevation of temperature. When first admitted the patient gave evidence of an acute infection, with enlargement of the spleen, but without cardiac involvement. During the course of the disease, however, in which the symptoms became progressively worse, chills, vomiting and finally convulsions, supervening. Signs pointing to pyelo-nephritis and finally endocarditis at the mitral valve, set in, and death followed shortly thereafter. During the course of the disease, repeated examinations of the blood for malarial organisms and several Widal reactions all proved negative.

Cultures from the blood were also taken twice during life, in both instances proving negative.

Autopsy showed acute ulcerative endocarditis of two segments of the aortic valve with vegetations, two small vegeta


tions on one of the flaps of the mitral valve, acute pyelonephritis, acute splenic tumor with one small splenic infarct, acute and chronic parenchymatous nejihi'itis.

Microscopically, diplococci, decolorizing by Gram, were found in the vegetations from the aortic valve, and a few decolorizing diplococci in the fiuid from the pelvis of the kidney. No cultures were taken.

The following case is reported by Loeb (Deutschcs Archiv fiir klinische Medicin, 1899, XXV, pp. 411-420). The patient, a man aged forty-one, consulted him for swelling and pain in the right fore-arm. Three weeks before he had had an urethral discharge, but, with the exception of rheumatic pains in the lower extremities, he had otherwise been healthy. During the course of the trouble, which at this time was mild, pleurisy and swelling of the ankle develoiied, and about two weeks later cardiac signs and symptoms, consisting at first of a soft systolic murmur, but shortly afterwards of loud blowing murmurs at all the cardiac orifices, with both systolic and diastolic murmurs in the mitral area. Higher temperature, chills, and enlargement of the spleen followed and were followed in turn by signs of hypostatic pneumonia and adherent pericardium. Death occurred shortly thereafter. At autopsy the layers of the pericardium were found bound together by friable adhesions. The left heart was somewhat dilated but not hypertrophied. Hard calcareous vegetations, attached to the posterior and right anterior segments of the aortic valve, and projecting into the ventricle, were found. The segments themselves were found thickened and perforated. The remaining valves were unaffected.

The lungs were oedematous but showed no infarcts.

The spleen was enlarged and showed an infarct abdut the size of a hazelnut.

The kidneys showed change, and there was a small red infarct in the right.

The bladder was negative.

From the vegetations on the affected valve large numbers of diplococci, morphologically similar to gonococci, and decolorizing by Gram's method, were found. Bacteriological examination of the affected synovial sacs and joints and the sidenic infarct were negative. No cultures were taken.

A most interesting case is reported by Bjelogolowij (Bolnitche Gazette, Bolkina, January, 1899, No. 4). The patient, a man aged 32, without history of inflammatory rheumatism or other disease except syphilis, was admitted complaining of palpitation and weakness of the heart and swelling of the right testicle, following gonorrhcea of one and one-half months' duration. According to the history the cardiac trouble had come on about two weeks before, and the epididymitis, which it proved to be, was of only a few days' standing.

On physical examination cardiac dulness was found somewhat increased, and at the apex two well-marked murmurs were heard, both being well transmitted. The pulse was collapsing in quality.

Course.- — At first the course of the disease was mild, but after several days chills, fevers, sweats, with weakness, vomiting, diarrhoea, pericardial pain and enlargement of the spleen came on, ending finally in the patient's death in collapse.

Autopsy. Anatomical Diagnosis. — Verrucose endocarditis of the tricuspid valve; ulcerative endocarditis of the aortic valve; catarrhal iineumonia; chronic hyperj^lasia of the spleen; ha?morrhagic infarcts of the spleen; cyanotic induration of the liver; hfemorrhagic infarction of the kidneys; catarrhal colitis; catarrhal enteritis.

Heart. — The pericardium contained several tablespoonfuls of a serous, transparent, yellow fluid. Fibrinous blood-clots were present and a little fluid blood. The walls were pale, of a graj'-red color and looked normal. On the xipper surface of


MAKCir, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


77


the tricuspid valve there were several soft, vi'art-like excrescences, of a reddish color, and about the size of a g:rain of corn.

The two posterior cusjjs of tlie aortic valve were fused, disfigured and tliickened with yellowish excrescences, which were covered on the surface with a friable and readily removable mass. The sinuses of Valsalva were dilated. The right cusp had a perforation the size of a goose-quill, filled with a bloody, fibrinous clot.

The mitral valve was normal.

Lungs. — Fibrinous pleurisy was present. Lungs otherwise negative save for a broncho-pneumonia at base.

Spleen. — Double its nornuil size, dark-colored, dense, trabeculse well marked, and presenting on the lower aspect at the edges a hajinorrhagic infarct the size of a hazelnut.

Liver. — Normal, yellowish-red color, fidl-blooded.

Kidneys. — Large, cai)sules strip with difficulty; the cortical layer of each kidney thickened and contains a discolored hcemoi-rhagic infarct the size of a pea. The tissue is darker than normal and there is pus present in the pelvis of each kidney.

The mucosa of the bladder, beyond being pale, seemed normal.

The stomach and intestines were normal save for a catarrhal colitis.

The knee and ankle joints .showed no change.

Phimosis was present. From the fossa navicularis a small drop of pus was expressed.

The testicles were without apparent change.

During life examinalion of the blood was made in the following waj's with these results:

1. Slide of blood, stained with methylene-bhu' and ensin, showed apparently diplocoeci, but this is doubtful.

2. A small drop of blood from the finger planted on gelatin and peptone-agar gave no growth.

3. One cc. of blood was obtained, under aseptic precautions, from the vein at the elbow, and three plates, consisting of two-thirds glycerin-agar and one-third hydrocele fluid, were successively inoculated.

After forty-eight hours over twenty whitish, punctate colonies developed on the three plates. In some -of these a darker center was noticed.


Microscopically, diplocoeci, resembling gonococci and decolorizing by Gram, were found.

Transplantation on gelatiii-agar and on bouillon gave negative results.

Transplantation on an h3drocele-agar slant gave a slowly developing, beautiful growth, resembling that of the gonococcus in all respects, and proving the presence of gonococci in pure culture in the blood.

After death bacteriological examination gave the following results:

1. About twenty-four hours after death culture from the heart's blood made on hydrocele-agar gave negative result.

2. Tubes of agar, bouillon, gelatin .■inil hydrocele-peptonglycerine-agar were inoculated with material obtained from the vegetations of the aortic valve; all with negative result.

3. Microscopical examination of the material from the vegetations of the aortic valve showed, however, diplocoeci completely identical with those found during life in the blood. These occurred both intracellular and extracellular, and decolorized by Gram.

4. No organisms were found microscopically on section of the splenic infarct.

Note Since the foregoing article has gone to press, a fourth case has

come under our notice in the Pathological Laboratory.

Autopsy No. 10:^0 There was a clear clinical history of an acute

gonorrha'al urethritis, for which the patient had come to the dispensary for treatment. At the end o£ a week he disapiieared, but returned in three months complaining of having had rheumatism of the joints, and pains in the chest and feeling generally unwell. He was at once admitted to the hospital under Dr. Osier's care, where his heart was found to be seriously involved. He died that night.

The autopsy showed an acute ulcerative endocarditis of the aortic valve, similar in character to that mentioned in Cases II and III. In coverslip preparations made from the vegetations micrococci were found having all the characteristics, morpho'logically and tinctorially, of Neisser's gonocoecus. Owing to an unavoidable lapse of time and to over-much handling of the heart, cultures proved an absolute failure on account of resulting contamination.

N. MacL. H. W. M. D.


AN EXPERIMENTAL STUDY CONCERNING THE RELATION WHICH THE PROSTATE GLAND BEARS TO THE FECUNDATIVE POWER OF THE SPERMATIC FLUID.

By George Walker, M. D., Instructor in Suryery, Johns EopUns University.


In order to eliicidttte more clearly the connection which the prostate gland holds to fertilization, I have instituted a series of experiments in which the gland in white rats was excised in part and in whole, and its effects on fecundity noted.

Steinach, in a series of investigations made to determine the function of the seminal vesicles, found that by an excision of them the breeding property was reduced about onehalf. When both pro.state and vesicles were removed, it was brought down to nil. lie did not excise the prostate gland alone, nnd could tluTfl'ore adduce no proof as to the part it played.


Eats were selected on account of the ease with which the gland could be removed, and also from the minimum amount of danger of injuring the seminal ducts; the two being in rodents quite distinct, and not connected. The gland consists of four, or sometimes six, distinct lobes; the two anterior ones are very much larger than the others; are pear-shaped, and stand well up and away from the urethra, being held by a fascia connected with the bladder. They communicate with the urethra by several small ducts whicli ein])ty into Iho roof of the Uunen just in front of the vesicle neck. The posterior lobes are somewhat triangular in shape, are more closely connected with the urethra, and


78


JOHNS HOPKINS HOSPITAL BULLP]TIN.


[No. UO.


are very mncli smaller and flatter, forming alimit onc-fonrlh of the whole gland. They extend slightly around the ejaeulal(ii-y ducts, and well up on the side of the ui-clhra. The two lateral lobes are only occasionally })resent, and seem to be developed from the posterior ones. A second glandular substance is connected with the inner side of the seminal vesicles, and presents the same macroscopic aj)pearance as does the prostate; Init on microscopic section it is shown to be a strui-ture similar to that of the vesicles.

The excision of the glands was done thus: The animals were etherized, the aljdominal wall was carefully sliaved and cleansed, and an incision made in the median line. This brought the anterior lobes into view, and by gently pulling the bladder forward and upward, they could very plainly be seen. They were very carefully separated from the liladder and from each other; a ligature was thrown around each, near the urethra, and both lobes excised; the posterior ones were exposed by pulling the bladder and seminal vesicles over the pid)es; they were then very carefully separated from the surrounding structures and teased by a pair of small forceps from their connection with the urethra. This occasioned only slight bleeding, which soon ceased without a ligature. The abdomen was closed by interru])ted silk sutures, the skin in the same manner, and the wound dressed with cotton and collodion. The animals usually made a rapid recovery, and appeared very lively on the following day.

The rats selected for ojteration were full grown, well de\eliiped, and in good physical condition. In several series the two anterior lobes were excised, and the effect on procreation noii'd. In the other series, all of the gland was removed, and the result also recorded.

The first series consisted of seven pairs; these were mated, and the number in the litter carefully noted. The two anterior lobes were then removed, and after sufficient recovery they were again mated.

Pair No. 1. Mated July 10th. Five w-eeks later the female gave birth to eight young; anterior lobes excised, and after recovery again mated Angust 23d; September 15th, a litter of eight was found.

Pair No. 2. Previously mated, and gave birth to ten young; two anterior lobes removed, and second mating August 24th. After two months, negative result.

Pair No. 3. Previously mated; five young. Anterior lobes excised and paired August loth. Six weeks afterwards, four young.

Pair No. 4.. Previously mated; eight young; removal of anterior lobes, and mated August 18th; after seven weeks, two young.

Pair No. 5. Previously mated; seven young. Anterior lobes excised, and second mating August 21st; after seven weeks, eight young.

Pair No. 6. Previously mated; eight young; anterior lobes excised, and mated second time August 23d; negative result.

Pair No. 7. Previous mating resulted in eight young;


removal of anterior lobes; second mating yVugust 30tli; negative result.

From ihc above it is seen that in two })airs the breeding was normal; in two others the nundicr was reduced to two in one case, and to four in the other, while in the remaining three the result was entirely negative.

A second series of fifteen pairs was taken; no jirevious mating, however, being done, as it had been ascertained by watching several other series that rats are fertile in nearly every instance. As in the preceding series, only the anterior lobes were removed ; after complete recovery they were paired with the females.

Pair No. 1. Positive result after five weeks; eight young.

Pair No. 2. Positive result after six weeks; seven young.

Pair No. 3. Positive result after six weeks; eight young.

Pair No. 4. I'ositive result after five weeks; five young.

Pair No. 5. Positive result after eight weeks; ten young.

Pair No. G. Positive result after nine weeks; eight young.

Pair No. 7. Positive result after four weeks; six young.

Pair No. S. Positive result after six weeks; seven young.

Pair No. !). Positive result after five weeks;' five young.

Pair No. 10. Negative result after three months and twenty-five days.

Pair No. 11. Negative result after three monllis and twenty-five days.

Pair No. 12. Negative result after three nuuiths and twenty-five days.

Pair No. 13. Negative result after three months and twenty-five days.

Pair No. 14. Negative result after three months and twenty-five days.

Pair No. 15. Negative result after three months and twenty-five days.

Afterwards tin" males were killed, and the seat of excision examined. In three of the fertile ones it could be seen that a small amount of the anterior lobes had been left, while in the others it had all apparently been taken away. In the ones which had proved unfertile, there was no part of the anterior portion present. In quite a number of them, and most notably marked in the ones which had proved fertile, the posterior lobe had increased in size. In the negative ones no such increase in size was apparent.

A third series of animals was selected and mated before operation. The ones which bred were chosen for the excision of the gland. At the first oper&tion only the anterior lobes were removed; they were again mated, and the fertile ones selected and subjected to a second operation in which all of the gland was taken away. The result is as follows:

Pair No. 1. Mated before operation; bred five. March 1st, removal of anterior lobes. Second mating March 5th. April 10th, bred three. April 12th, removal of the remaining gland; again mated; negative resiilt.

Pair No. 2. Previous to operation bred eight; removal anterior lobes March 1st; mated March 4th; negative result. Second opcralinn, entire removal April loili; negative result.


March, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


79


Pair No. 3. Before operation bred four. First operation February ISth; mated March 3d. April 3d, bred seven. Second operation April 2-lth; entire removal. Mated April 26th; negative result.

Pair No. 4. Before operation bred seven; operation, removal anterior lobes March 1st; mated March 3d; April 22d, bred four. Complete removal April 2-4th; mated April' 2Gth. After six weeks, positive result; bred six.

Pair No. 5. Before operation bred six; removal anterior lobes March 1st; mated March 3d; April 15, bred six. Second operation May 7th; complete removal; negative result.

In the above series, four out of the five were fertile after the first operation; number two being negative after the first and after the second. In two the number was normal, but in the remaining two pairs, the number was decreased in one case from five to three, and in the other from seven to four. In one pair, however, number three, it was increased from four to seven. After the second operation, four out of the five were sterile, only one bred.

The autopsies showed in the four barren ones that the gland had been entirely removed, whereas in the fertile ones, about three-fourths of the posterior lobes had not been excised.

In order to determine whether the seminal ducts had been injured during operation, and thus had prevented the outflow of the seminal fluid, a careful examination of both orifices and canals was made; they were found in each instance to be patent; moreover, on gently squeezing the seminal vesicles the secretion freely oozed through the orifices, and on stripping the vasa deferentia, the secretion freely exuded from the openings. The fluids thus obtained were examined microscojjically and found to contain spermatozoa.

A fourth series of eleven pairs was selected, and the entire gland removed at one sitting. These, after recovery, were mated, with the result below recorded. It should be noted that the females had been kept for a long time separate, so that it was made sure that no fertilization was present.

After sufficient length of time proved nega Negative. Negative. Negative. Negative. Negative. Negative. Negative.

After six weeks, positive result; three young. After seven weeks, two young. After five weeks, five young. It will thus be seen that in the eleven cases, eight were entirely negative, and in the remaining three, there was not a full litter in any instance; five being the nearest approach to it; in the other two the litter being two and three respectively.

The autopsies of Nos. 1, 2, 3, 4, 5 and G, showed a com


Pair No.


1.


Pair No.


2.


Pair No.


3.


Pair No.


4.


Pair No.


5.


Pair No.


6.


Pair No.


7.


Pair No.


8.


Pair No.


S).


Pair No.


10.


Pair No.


11.


plete removal of the gland; No. 7 presented a small piece of the lateral lobe; No. 8 showed only a slight trace of the left lobe; No. 9 showed fully three-fourths of the posterior lobes present, and a moderately sized stump of the anterior ones; in No. 10 there was found a large lateral lobe which had not been excised. In No. 11, although a positive result was obtained, there was apparently no gland left, either posterior or anterior. This last case was the only example in the whole series in which the male had proved fertile with no portion of the gland remaining.

The examinations proved that in most of the negative pairs there had been a complete removal of the gland; in two eases, however, some of it was present, while in the fertile ones, two presented large remnants of the gland which had failed to be excised; in one instance, all had apparently been removed. A similar examination as to the patency of the seminal ducts was made, and in only one instance was an occlusion found, and in that it was in only one duct. The others were perfectly open, and emitted their secretion.

The sexual desire and capacity of the rats were carefully noted both in those in which a partial excision, and in those in which a complete excision had been done. The examination was made by carefully watching them for some time each day after they were mated, subsequent to the operation. In every instance, the males were as sexually active after the operation as before; and in no instance was the capacity diminished.

The animals in which a complete removal of the prostate gland had been done were kept from four to seven months after the operation in order to ascertain whether any effect had been produced on the testes by the removal of the gland. At the end of this time the animals were killed with chloroform, and the organs carefully removed and examined. In every instance they were of normal size, of natural consistency, and in no way did they differ from the usual type. They were preserved in Zenker's fluid, and the subsequent microscopic sections did not reveal any changes.

In order to determine whether any effect was produced in the development of the testes by a very early removal of the prostate gland, I selected a certain number of young and healthy males, just at the age when the gland was beginning to develop; another series of about the same age being kept as controls. The prostate glands in the first number were entirely excised; the animals were kept for nearly six months, by which time they were thoroughly grown. They were then killed, and the testes upon examination were found to have developed normally; and they presented the same apjiearance and feel as were present in the other series of rats which were kept as controls. These were also examined microscojiically, and no difference was found in them. The seat of the ojieration was examined; in one there had been a partial development of the gland; in the others no trace of it was discernible.

SUJIMART.

First series of seven pairs; anterior lobes excised; two bred normally, two had small litters, two were negative.


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JOHNS HOPKINS HOSPITxlL BULLETIN.


[No. 120.


Series No. 2. Fifteen jjairs; anterior lobes removed; nine bred normally, five proved negative, one escaped.

Series No. 3. Five pairs; after first operation, removal of anterior lobes; four out of five bred normally; one was negative. After a second operation wliere complete removal was done, one bred normally, four were negative.

Series No. 4. Eleven pairs; complete removal of the gland at one sitting; eignt were negative, three had small litters; none positive.

Series No. 5. Prostate gland removed in early life, did not have any effect on the subsequent development of the testes.

Conclusions.

From the above experiments, the following conclusions can safely be drawn:


First. That a removal of the anterior lobes of the prostate gland in rats has no effect on breeding; but in a certain number it diminishes the fecundating power; and in a few it is destroyed entirely.

Second. Complete excision has a very marked effect on fecundity, reducing it to almost nil when the gland is en•tirely removed.

Third. Partial or complete removal of the prostate has no effect upon the sexual desire and capacity.

Fourth. Complete removal of the gland in the adult animal has no effect on the liistological structure of the testicles. Complete removal of the prostate in the young animal has no effect upon the subsequent development of the testes.


SUMMARIES OK TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.


Charles Russell Baedeen, M. D. Casto-Vertebral Variation in Man. — Anatomischer Anzeiger, November 7, 1000.

Simon Flexner, M. D. Nature and Distribution of the New Tissue in Cirrhosis of the Tjiver (Preliminary Cnntmunication). — Proceedings of Ihe Pallwlogical Sorieiij of Philudelphia, November, 1900.

William Osler, M. D. An Address on John Locke as a Physician. — Lancet, London, October 20, 1900.


Howard A. Kelly, M. D. A Eapid and Simple Operation for Gail-Stones Found by Exploring the Abdomen in the Course of a Lower Abdominal Operation. — Ulediral Neil's, December 22, 1900.

Henry J. Berkley, M. D. Clinical Cases. VIL The Pathology of Chronic Alcoholism. — The Ainericaii Journal of Insaniiij, January, 1901


FURTHER OBSERVATIONS ON EPINEPHRIN.

By John J. Abel, M. D.,

Professor of Phaniiaruloij!/. Johns Ilophins Unirersifi/.


Shortly after tlie publication of my last paper on e[)inephrin,' I began to try simpler methods for the isolation of this substance, methods which sliould avoid the process dl benzoating and the subsequent liydrolysis in the autoclave. Although the highly active bisulphate that was secured by these simpler methods was considerably contaminated with cholin and witli compounds of the xanthin series, these attempts nevertheless taught me that the autoclave product as formerly described differs in several important particulars from that obtained without benzoating or subsequent hydrolysis. The latter product, which I might term unaltered or native epinephrin, is not precipitated by ammonia and fails to give many of the alkaloidal reactions which are characteristic of the autoclave product.

At first glance it might appear tliat the epinephrin hitherto described by me was a mixture of two different substances, one of which is precipitable by ammonia: the other, a jijiysin


' Zeitschr. f. pbysiol. CUcm., B:l. xxviii, 3. ."IS.


logically active, pyrocatechin-like substance, not possessing this projierty: and this is in fact the view taken by v. Fiirth " in a ]iaper in whicli he comments on my results. This author, using a modification of the earlier methods of Holm' and Krukciilierg ' ju'ecipitates opiiu'iibrin with ammonia and a lead or zinc solution, suspends t.he resulting ju'ccipitate in methyl alcohol and decomposes it with concentrated sulphuric acid.

In fliis way he obtains a methyl-alcohol solution of a sulphate which has not been subjected to hydrolysis, and since it differs in several important particulars from epinephrin as described by me, he concludes (hat we are dealing with two different substances. He considers the term epinephrin to be applicable to a substance that is physiologically inactive, precipitable by ammonia, devoid of chromogenic properties, incapable of reducing silver nitrate or of forming a compound


'Zeitsclir. f. ph}-siol. Cbem., Bd. xxix, s. 10.5. 3 Journ. f. pract. Chemie, Bd. c (18C7), s. 1.50.

Vircliow's Arcliiv, Bd. ci (18S.5), s. 543.


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with ferric chloride, while he applies the name suprarenin to the well known chromogen or physiologically active substance which in its native condition is non-precipitable by ammonia, reduces silver nitrate, yields an iron compound of specific qualities, fails to give a series of alkaloidal reactions characteristic of hydrolyzed epinephrin, and on fusion with potassium hydrate yields no odor of indol or skatol. Such, in brief, according to v. Fiirth, are the main characteristics of what he calls two different substances.

I propose in this paper to take up the main points presented by V. Fiirth and I hope to show that differences of method are alone responsible for the variations he has noted. What V. Fiirth calls suprarenin is native or unaltered epinephrin.

I. Precipitation by Ammonia.

Epinephrin obtained by hydrolyzing its benzoyl compound is precipitable from an aqueous solution by ammonia in the form of yelluwish-white flocks which rapidly darken on exposure to the air and which are physiologically inactive. And here it may be remarked that complete precipitation of a salt of epinephrin is attended with some difficulty. The fractional method must be used in order to avoid an excess of ammonia, and toward the end of the operation, when only a little of the chromogenic substance remains, it is necessary to concentrate the solution with the help of the vacuum desiccator before the final precipitation is made. The various precipitates may be washed with ice-water, although it must be borne in mind that prolonged washing will dissolve almost all of the fiocculent precipitate with the exception of a small amount of a dark insoluble residue which has become oxidized by long exposure to the air. When the fractional precipitation has been properly conducted the final filtrate from a solution of epinephrin bisulphate, for example, will contain nothing but ammonium sulphate, while on the various filters will be found all of the chromogenic substance.

Now, epinephrin, the chromogenic substance of the suprarenal gland, whether isolated by v. Fiirth's or any other method that does not involve hydrolytic treatment, becomes immediately precipitable by ammonia as soon as such hydrolytic treatment is applied. Proof for this statement is found in the following facts:

1. The iron compound of " suprarenin " was prepared according to V. Fiirth's method, which I consider a distinct contribution to our knowledge of the subject. His directions were followed with the exception that the compound was redissolved and reprecipitated out of acidulated methyl alcohol in order to remove as far as possible impurities that might be present. I then made benzoyl and acetyl epinephrin from this iron compound, and on saponifying these derivatives in the autoclave, I found that the resulting solutions yielded fiocculent, inactive epinephrin on the addition of ammonia; in other words, they behaved exactly like compounds of the same name formerly described by me.

2. By cautiously adding ammonia to the methyl alcohol solution from which v. Fiirth prepares his iron compoimd. I removed all excess of sulphuric acid and then drove off the


methyl alcohol in the water bath. The residue was now taken up in water, filtered and heated in the autoclave for two hours in the presence of a little sulphuric acid and under a pressure of four atmospheres. The solution, which at first gave no precipitate with ammonia, now yielded an abundant fiocculent preci^^itate on the addition of this reagent. Furthermore, I dissolved the iron compound in methyl alcohol containing a little acetic acid and removed the iron by repeated treatment with hydrogen sulphide. After evaporation of the methyl alcohol the residue was taken up in water, a little dilute sulphuric acid was added and this solution was hydrolyzed as before. Here again, the same result was obtained. The solution, which before treatment in the autoclave gave no precipitate with ammonia, now yielded epinephrin in abundance.

3. It might be asserted that the above facts are capable of another interpretation, that the substance which on hydrolysis yields this fiocculent precipitate is not the chromogenic substance of the siiprarenal capsule but an entirely different body which on precipitation drags down the chromogenic substance with it; that it is in fact merely present in v. Fiirth's iron compound as an impurity. But my experiments with the active bisulphate of epinephrin, which can be converted quantitatively into this fiocculent substance (barring small losses by conversion through oxidation into an insoluble form), fully prove that a separation of this body into a chromogenic and a non-ehromogenic substance is impossible. It is itself, as stated in my earlier papers, an inactive modification of the active substance of the suprarenal gland. A further proof of this assertion is seen in the following: A chemist in the employ of one of our manufacturing firms has recently sent me about 1-10 of a gram of a micro-crystalline compound derived from the suprarenal gland that possessed a high degree of physiological activity and gave all the specific reactions of the native non-hydrolyzed form of the active principle. The method of its manufacture has not been made public and I have not as yet determined whether the compound represents the free base itself or some crystalline derivative.

This compound, which dissolves only sparingly in cold water, also fails to give a precipitate with ammonia unless subjected to treatment in the autoclave, behaving, therefore, like all specimens of the chromogen thus far isolated.

In short, it is an inherent property of the active principle of the suprarenal gland, prepared by whatever method, to fall out in the form of a fiocculent, physiologically inactive precipitate on the addition of ammonia after previous treatment in the autoclave.

It is not surprising that v. Fiirth should have failed to note this property of epinephrin inasmuch as he did not test any of my compounds as made by saponification of the benj zoyl derivative, in respect to their preeipitability by ammonia, ' but applied this test only to solutions obtained by decom; posing his ammoniaeal lead on ammoniacal zinc precipitates. j The substance obtained by him from these solutions on the addition of annnonia is not epinephrin; it is either some de


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generate product of it or an entirely different substance. His observation that tiie active principle in its native state is not precipitable by ammonia is, however, entirely correct.

II. On the Ihon Compound of Epinephrin.

Now that it has been shown that some of the properties of epinephrin, as heretofore described, are not inherent in the native substance but are developed by chemical manipulation, it is of -interest to inquire into the behavior of its two chief modifications toward iron salts.

As before stated, v. Fiirth has shown that a solution of the active I'rinciple in methyl alcohol yields a highly active precipitate on the addition of ferric chloride and ammonia, aud that the addition of ferric chloride to a dilute aqueous solution containing a little acid gives a bright green color, while if the solution is alkaline, a carmine red color is the result.

Up to this time no analyses of this iron compound or of its derivatives have been given, nor are we informed whether its iron content varies on re-solution and re-precipitation, nor how far variability in this respect is affected by dilferent modes of manipulation.

This author also appears to believe that the salts of epinephrin described in my previous papers are incapable of yielding an iron compoimd except as the chromogen is present as an impurity. But the experiments presently to be described show that epinephrin bisvilphate is quantitatively convertible into an iron compound indistinguishable in appearance and chemical reactions from that described by v. Fiirth, although differing in two respects from his compound: first, in that it can be precipitated directly from an acidulated aqueous solution of epinephrin, and second, that it is physiologically inactive. These differences, however, like others already alluded to, are due solely to differences in previous manipulation; in short, the conditions here are the same as in the ease of the precipitation by ammonia, for if the methyl-alcohol solution from which v. Fiirth derives his iron compound be taken and the methyl alcohol expelled, the residue dissolved in water, acidulated with a little dilute sulphuric acid and treated in the autoclave as already described, a transformation into what I have hitherto called epinephrin will be formd to have occurred.

After removal from the autoclave the solution still possesses a high degree of physiological activity, but the addition of ferric chloride and ammonia now yields a precipitate, the iron compound of epinephrin, which is physiologically inactive. Here, too, the hydrolytic action of the autoclave is responsible for an inactive form of the iron compound, capable of precipitation out of acidulated aqueous solutions of the active principle.

conversion of epinephrin bisulph.\te into an iron compound.

The following experiment was made with 1.197 grams of pure epinephrin bisulphate, another portion of which had served as the source of the phenylcarbamic di-ester of epi


nephrin described by me in an earlier paper." The salt was dissolved in very dilute sulphuric acid, and ammonia was cautiously added until about two-thirds of the epineplirin was precipitated in two fractions in the form of yellowish-white flocks. These were repeatedly wa.shed with ice water and the washings were added to the original filtrates. The flocculent precipitates were now separately dissolved in very dilute sulphuric acid and converted into an iron compound by the addition of ferric chloride and the siibsequent addition of ammonia to very near the neutral point.

These jirecipitates were repeatedly washed by sedimentation in tall cylinders until the ammonium sulphate was entirely removed.

The compound was then redissolved in dilute sulphuric acid, reprecipitated with ammonia and washed as before, collected on a filter and dried over sulphuric acid.

The filtrates from the precipitations by ammonia together with the washings were also converted into the iron compound, which, after being washed in a tall cylinder by sedimentation, was redissolved in very dilute sulpluiric acid, reprecipitated by ammonia and washed till all traces of sulphuric acid had disappeared.

In this connection it may be remarked tliat the washing of the iron compound as above described until it is free from ammonium sulphate aud sulphuric acid is accomplished with difficulty. Large quantities of water are required and the amoimt of the iron compound which remains in solution in the supernatant fluids depends of course upon the reaction of these fluids. This reaction, I may remark, is difficult to maintain at the same level in the several cases. Usually the wash fluids were colorless, but even then the addition of ammonia caused a farther precipitation of the iron compound. It is to be noted, also, that the iron content of the compound here considered varies with the conditions of its precipitation. Thus, if the iron content of a given fraction is 8.50,'^, that precipitated from its washings may be as high as 12.62;^, or even higher, and this same variability is met with if the portion on the filter is redissolved and reprecipitated. Whether this variability also attaches to the physiologically active iron compound obtained by the use of methyl alcohol has not yet been determined.

Briefly stated, the results of the above experiments are as follows: 1.197 grams of epinephrin bisulphate made from the benzoyl compound were treated with ammonia until the larger portion of the epinephrin was precipitated; this was washed with cold water and the washings added to the original filtrates. Both the flocculent free epinephrin and that which still remained as a bisulphate in the filtrates were converted into an iron compound. According to v. Fiirth. only the filtrate and the washings from the free epinephrin could yield an iron compound. Yet after all the manipulations above described the following fractions of this iron compound were obtained:


s Amer. Joiiru. of Plijsiol., vol. iii, 1S<)9-1!I00, No. 8, p. XVII.


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From epincphriii, Precipitate I.

0.1412 gram.


Fiom epinephriii, Precipitate II.

0.3845 g-ram.


From the filtrates from Precipitates I and 11.

0.3438 gram.


From the wasliings of those precipitates further amduiits of the iron compoimd were obtained and in relatively the same proportion in each case. These additional fractions, together with what was recovered from filter papers, cylinders and funnels, bronght the total amonnt of the iron componnd obtained up to 0.9212 gram. A small quantity, amounting to perliaps 0.02 gram was further precipitated from the washings of the last fraction and was not taken into consideration.

The object of the above experiment was to learn whether this compound can be as easily made from floceulent, inactive epinephrin as from its filtrates, but the fact which incidentally appeared, that notwithstanding the inauy manipulations involved, so large an amount as 0.9242 gram of an iron compound was obtained from the above-mentioned quantity of bisulphate, fairly warrants the statement that epinephrin bisulpliate is quantitatively convertible into an iron compound.

In tlie case of the iron compound from epinephrin. Precipitate IT, and from the filtrates from epinephrin. Precipitates I and II, like conditions of precipitation were maintained both in respect to the amounts of the reagents employed and the reaction of the wash fluids, with the result that the iron content of the two fractions was nearly the same. This is shown in the following table:


Iron compound

from ciiinephrin,

Precipitate U.

0.110.5 gm. burned on an ashless tilter left 0.014 gm. Fe.^Oj = 8.87 per cent Fe.

0.174 gm. burned in a curi'ent of oxygen, left 0.031 gm. Fe„Os = 8.44 Fe.


Iron compound from filtrates

Irom ciiinephrin.

Precipitates 1 and II.

0.09(1.5 gm. b\irned on an ashless filter left 0.0133 gm. Fe^O, = 8.8.5 per cent Fe.

0.1473 gm. burned in a current of oxygen, leftO.OlSO gm. Fe.fl3= 8.06 per cent Fe.


The carbon and hydrogen content of the two fractions was also in fairly close agreement, but the analyses are reserved for consideration in a later paper in which I hope to give a fuller comparison of this compound and that made by v. Fiirth in the manner already described. A single analysis of a specimen of tlie latter compound was made and it was found to contain 12.8 per cent of iron.

This higher iron content unaccompanied by other data affords no basis of comparison between the two substances; for, as we have seen, a fraction of my iron comjtound which contains 8.5 per cent of iron may by chemical manipulation have its iron content raised to over 12 per cent.

In conclusion, then, it may be stated that an active salt of epinephrin made by saponification from its benzoyl compound is convcrtiljle into an iron compound, both in metliyl alcohol and in aqueous solution.

When made from an aqueous solution this iron compound is physiologically inactive, also less soluble in dilute acetic acid than v. Fiirth's compound, but in respect to its chemical reactions it is indistiuguishable from his coinjiound.

By benzoating the iron compound of v. Fiirlli, trial cxjieri


ments have shown me, that the entire series of derivatives formerly described by me may be obtained. From it I have also made the acetyl compound and by decomposing it in the autoclave I have obtained an active bisulphate indistinguishable in appearance and reactions from that formerly described by me.

Our compounds also agree in yielding, on the addition of moderately strong alkali, the volatile base of a coniinepiperidine-like odor so often noted in my previous papers.

III. Other Effects of Treatment in the Autoclave.

V. Fiirth has also stated that the active ])rinciple of the gland as contained in the fluids prepared from his lead or zinc precipitates, yields no precipitates on the addition of certain alkaloidal reagents, as picric, phosphotungstic or tannic acid, iodine in potassium iodide or concentrated solution of zinc chloride.

It is, however, easy to prove that here, too, as in the instances relating to precipitability with ammonia and with ferric chloride, we are dealing with characteristics which only require appropriate treatment for their development. If the iron compound prepared according to the directions of v. Fiirth is converted into the acetyl derivative and this is saponified in ihe autoclave, a solution is obtained from which the epinephrin bisulphate formerly described by me can be prepared without difficulty. Aqueous solutions of this salt readily give precipitates with the above-named alkaloidal reagents, while solutions which are derived 'from the material from which v. Fiirth's iron compound is prepared, that is to say, from material which has not been exposed to hydrolysis, fail to give jjrecipitates with these reagents.

A further instance of this behavior is ftirnished by the compound already alluded to as having been sent to me by the chemist of one of our manufacturing firms. Before treatment in the autoclave with dilute sulphuric acid this substance also yields no precipitate with such alkaloidal reagents as picric acid, phosphotungstic acid, iodine chloride or iodine in potassium chloride, but after such treatment a prompt precipitation occurs on the addition of these reagents.

IV. Skatol: a Decomposition Product of Epinephrin.

I have stated in previous papers that on fusing the chromogen of the gland with powdered potassium hydrate and then diluting with water the penetrating odor of skatol arises from the solution. "When this solution of the fusion products was shaken with ether and the ether allowed to evaporate, little globules remained, having an intensely fsecal odor and giving the characteristic reactions of skatol with sufllcicnt definiteness to warrant the belief 'that this substance is a decomposition product of the active principle under the conditions specified.

V. Fiirth has failed to substantiate my statements in this particular, but the tests which I have made with the acetyl compound prepared directly from his own iron compound, as also with a specimen of epinephrin bisulphate prepared


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[No. 120.


from this acetyl derivative have still further convinced me that my statements were correct. In order to get olfactory evidence of the presence of skatol, it is only necessary to smelt about 0.1 gram of either of these compounds in a cautious manner with an appropriate amount of powdered potassium hydrate, the two reagents being spread out on the bottom of an Erlenmeyer flask, then to dilute with water, shake with ether, and evaporate the ether out of a Urechsul wash bottle with the help of a suction pump. The water contained in the ether is left behind as ice and the low temperature produced is an eifectual bar to the complete escape of the skatol. On opening the wash bottle after the removal of the ether one obtains sufficient proof that skatol is present from its characteristic odor.

V. Analytical Considerations.

It would now be in order to give analytical data to illustrate the changes that occur in the autoclave and to show what relation obtains in respect to elementary composition between the autoclave product and its less manipulated, physiologically more active counterparts. But an accident that haj)])encd to me in my laboratory in the early days of December and which for nearly three months kept me from my laboratory has made more than an introductory discussion of this point impossible.

It would appear that the simplest method of arri\ing at a conclusion in regard to the extent of the analytical differences existing between epinephrin as made by the autoclave method and that made by avoiding this treatment, would be to analyze the acetyl derivative when made from v. Fiirtlfs iron compound. The direct conversion of this iron compound into its acetyl derivative contends with the difficulty of purifying and washing the former substance in consequence of its amorphous character, and is also open to the suspicion that secondary changes, such as oxidation, may occur in the process of acetylizing. I have nevertheless converted^ this iron compound into its acetyl derivative, without first removing the iron. Preliminary analyses have shown that its nitrogen content varies from 4.18 to 4.88 per cent. My empirical formula, for triacetyl epinephrin as made by the autoclave method, calls for 3.31 per cent N. In the above instances the nitrogen content was determined by the method of Kjeldahl, and the observed deviation from the theoretical requirements are too large to bring the acetyl compound now under consideration into a simple relation with that formerly described by me.

It may be remarked in passing that the observed results vary still more widely from those found by v. Furth, who gives 5.71 per cent as the average nitrogen content of his acetyl compound, while the theoretical requirement is either


5.81 or 5.86 per cent, according as the one or the other of his assumptions that the active principle is tetrahydrodioxypyridin or dihydrodioxypyridin is made the basis for the empirical formula.

At tlic present moment it is impossible to express, in analytical terms, the differences that exist between the epinephrin of my former papers and the somewhat less altered, native principle. Their cpialitative differences and resemblances have been pointed out in this paper. AVhile it is perhaps unwise to anticipate the results of future researches, I would suggest that one or more of the following chemical changes may possibly account for the differences that have been noted: 1. The saponification of the benzoyl derivative may not be a complete one; one benzoyl group may have been retained, in which case my epinephrin would represent the monobenzoyl derivative of the native principle. 3. Inasmuch as treatment in the autoclave of every form of the active principle, no matter how prepared, leads to the appearance of new properties, it is in order to ask whether the entrance of one or more molecules of water into the compound, or the loss of an atom of nitrogen in the form of ammonia or a combination of these two alterations, will not be foinid to lie at the bottom of the whole difficulty. In case one or both of these changes take place, they would of course also occur in the case assumed under 1. 3. It is also possil)le that the autoclave is responsililc for a doubling of the original molecule after previous elimination of water and also of nitrogen in the form of ammonia or of a simple anime.

These and other points will constitute the subject matter of a future communication. The methods that have hitherto been employed by me have served their purpose in giving us unstable but characteristic derivatives of the native principle. These have retained a high degree of physiological activity and give all the known reactions of the native product, but they show, in addition to these, certain new reactions, such as precipitability by ammonia and by alkaloidal reagents.

In conclusion I would state that the autoclave is also responsible for a decrease in the physiological activity of the compound. This is shown by the data recently obtained by Prof. Reid Hunt" with a specimen of unaltered epinephrin bisul])hate, which was prepared from v. FiirtlTs lead precipitate, by removal of the lead and su1)sc(pient fractional precipitation. Other methods of isolation in which also the use of the autoclave plays no part are now in progress in my laboratory, and detailed statements as to the composition and physiological activity of the resulting products will follow later.


6 Amer. Jour, of Physiol., vol. v, No. 2, p. VII.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

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JOHNS HOPKINS HOSPITAL BULLETIN.


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THE JOHNS HOPKINS MEDICAL SCHOOL.

FACULTY.


Daniel C. Gilmax, LL.D., President.

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ADMISSION TO ADVANCED STANDING.

Applicants for admission to advanced standing must furnish evidence (1) that the foregoing terms of admission as regards preliminary training have been fulfilled, (2) that courses equivalent in kind and amount to those given here, preceding that year of the course for admission to which application is made, have been satisfactorily completed, and (3) must pass examinations at the beginning of the session in October in all the subjects that have been already pursued by the class to which admission is sought. Certificates of standing elsewhere cannot be accepted in place of these examinations.

SPECIAL COURSES FOR GRADUATES IN MEDICINE.

since the opening of the Johns Hopkins Hospital in 1889, courses of instruction have been offered to graduates in medicine. The attendance upon these courses has steadily Increased with each succeeding year and indicates gratifying appreciation of the special advantages here afforded. M'lth the completed organization of the Medical School, it was found necessary to give the courses intended especially for physicians at a later period of the academic year than that hitherto selected. It Is. however, believed that the period now chosen for this purpose Is more convenient for the majority of those desiring to take the courses than the former one. The special courses of Instruction for graduates In medicine are now given annually during the months of May and June. During April there is a preliminary course in Normal Histology. These courses are Iu I'athology, Bacteriology, ciiuical Microscopy. General iledicine. Surgery. Gynecology, Deriiiatologj', Diseases of Cluldren, Diseases of the Nervous System, Genito-Urinary Diseases, Laryngology and Rhlnology, and Ophthalmology and Otology. The instruction is intendid to meet the requirements of practitioners of medicine, and Is almost wholly of a practical character. It includes laboratory courses, demonstrations, bedside teaching, and clinical instruction in the wards, dispensary, amphitheatre, and operating-rooms of the Hospital. These courses are open to those who have taken a medical degree and who give evidence satisfactory to the several instructors that they are prepared to profit by the opportunities hero offered. The nuiiibcr of students who can be accommodated in some of the practical courses is necessarily limited. For these the places are assigned according to the date of application.

During October a select number of physicians will be admitted to a special class for the study of the Important tropical diseases met with la this region.

The Annual Announcement and Catalogue will be sent upon application. Inquiries should be addressed to the

REGISTRAR OF THE JOHNS HOPKINS MEDICAL SCHOOL, BALTIMORE.


86


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[No. 130.


PUBLICATIONS OF THE JOHNS HOPKINS HOSPITAL.


THE JOHNS HOPKINS HOSPITAL REPORTS.

Volume I. 423 pages, 99 plates.


Volume II. 570 pages, with 28 plates and figures.


Volume III. 766 pages, with 69 plates and figures.


Volume IV. 504 pages, 33 charts and illustrations.

Report on Typhoid Fever.

By William Osler, SI. D.. with additional papers by W. S. TnAYEB, M. D., and J. Hewetsox, M. D.

Report In Neurology,

Dementia Paralytica In the Negro Kace: Studies In the Histology of the Liver; The Intrinsic Palmonary Nerves In Mammalia; The Intrinsic Nerve Supply of the Cardiac Ventricles in Certain Vertebrates; The Intrinsic Nerves of the Submaxillary Gland of M}is musciihis ; The Intrinsic Nerves of the Thyroid Gland of the Dog; The Nerve Elements of the Pituitary Gland. By Henry J. Berklev, 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. Halsted, M. D.

Report In Gynecologry,

Hydrosalpinx, with a report of twenty-seven cases; Post-Operative Septic Peritonitis; Tuberculosis of the Endometrium. By T. S. Cdllen, M. B.

Report in Pathologry.

Declduoma Malignum. By J. Whitridge Wiluaus, M. D.


Volume V. 480 pages, with 33 charts and illustrations.

CONTENTS: The Malarial Fevers of Baltimore. By W. S. Thater, M. D., and J. Hewet so.s, M. D. A Study of some Fatal Cases of Malaria. By Lewellys F. Barker, M. B.

Studies in Typlioid Fever.

By William Osler, M. D., with additional papers by G. Bldmer. M. D., Simon Flexxer, M. D., Walter Keed, M. D., and H. C. Parsons, M. D.


Volume VI. 414 pages, with 79 plates and figures.

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 III.— Rlcin Poisoning.— Experimental Lesions induced by Acute Hlcln Poisoning. 2. Experimental Lesions Induced by Chronic Rlcin 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 Rlcin Intoxication; Nerve Fibre Terminal Apparatus; Asthenic 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. Cullen, M. B. Pregnancy In a Rudimentary Uterine Horn. Rupture, Death, Probable

Migration of Ovum and Spermatozoa. By Thomas S. Collen., M. B., and

G. L. WiLKiNS, M. D. Adeno-Myoma Uteri Diffusum Benignum. By Thomas S. CmxEH, M. B.


A Bacteriological and Anatomical Study of the Summer Diarrhoeas of

Infants. By William D. Booker. M. D. The Pathology of Toxalbumln Intoxications. By Simon Flexner, M. D.


Volume VII. 537 pages with illustrations.

I. A Critical Review of Seventeen Hundred Cases of Abdominal Section from the standpoint of Intraperitoneal Drainage. By J. G. Clark, M. D. n. The Etiology and Structure of true Vaginal Cysts. By James Ernest Stokes. M. D.

III. A Review of the Pathology of Superficial Burns, with a Contribution to our Knowledge of the Pathological Changes in the Organs in cases of rapidly fatal burns. Bv Charles Russell Bardeen. M. D.

IV. The Origin, Growth and Fate of the Corpus Luteum. By J. G. Clark, M. D.

V. The Results of Operations for the Cure of Inguinal Hernia. By Joseph C. Bloodgood, M. D.

Volume VIII. 552 pages with illustrations.

On the role of Insects, Arachnids, and Myriapods as carriers in the spread of Bacterial and Parasitic Diseases of Man and Animals. By George H. F. NuTTALL, M. D., Ph. D.

Studies in Typlioid Fever.

By William Osler. M. D., with additional papers bv J. M. T. Finney. M. D., S. Flexner. M. D., I. P. Lyon, M. D., L. P. Hamburger, M. D., H. W. Cdshing. M. D.. J. F. Mitchell, M. D., c. N. B. Camac M. I)-. X. n. Gwtn M. i)., Charles P. Emerson, M,D., H. H. Young, M. D.. and W. S. Tuatkr.HI.D


Volume IX. 1060 pages, 66 plates and 210 other Illustrations.

Contributions to the Seienee of Medicine.

Dedicated by his Pupils to William Henry Welch, on the twenty-fifth anniversarv of his Doctorate. This volume contains 3S separate papers.


The set of nine volumes -will be sold for fifty dollars, net. Volunie-s 1 and II ■ivill not be sold separately. Volumes III, IV, V. VI. VII and VIII will be sold for five dollars, net, each. Volume IX ^vill be sold for ten dollars, net.


SEPAR.\TE MONOGRAPHS REPRINTED FROM THE JOHNS HOPKINS HOSPIT.\L, REPORTS.

Studies in Dermatology, By T. C. Gilchrist, M. D., and Emmet Kixford,

M. D. 1 volume of 164 pages and 41 full-page plates. Price, in paper. $3.00. The Malarial Fevers of Baltimore. By W. S. Thayer, M. D., and J.

Hewetson, M. D. .\iifl A Study "of some'Fntal Cases of Malaria.

By Lewellys F. Barker, M. B. 1 vohime of 2S0 pages. Price, in paper, $2.75.

Pathology of Toxalbumin Intoxications. By Simon Flexner, M. D.

1 volume of 150 pages with 4 full-page lithograplis. Price, in paper, $2.00.

Studies in Typlioid Fever. I, II. By William Osler, M. D., and others,

E-xtracted from \'ols. IV and V of The .Johns Hopkins Hospital Kepurts. 1

volume of 481 pages. Price, in paper, $3.00. Studies in Typhoid Fever. III. By William Osler, M. D., and others.

Extracted from Volume \'III of The Johns Hopkins Hospital Reports. One

volume of 400 pages. Price, in paper, $3.00.


THE JOHNS HOPKINS HOSPITAL BULLETIN.

The Hnspital liullrtin contains details of hospital and dispensary practice; abstracts of papers read and other proceedings of the Itedical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work of the Hospital. It is issued monthl3\ Volume XII is now in progress. The subscription price ig $1.00 per year. The set of twelve volumes will be sold for 523.C0.

Orders should be addressed to

The Johns Hopkins Press, Baltimore, Md.


STUDIES IN TYPHOID FEVER

SERIES I-II-III.

The papers on Tj-phoid Fever, edited by Professor William Osier, M. D., and printed in Yolunies IV, V and YlIT of The Johns Hopkins Hospital Eeports have been brought together, and bound in cloth.

The volume includes thirty-five papers by Doctors Osier, Thayer, Hewetson, Blumer, Flexner, Read, Parsons, Finney, Gushing, Lyon, ]\Iitchell, Hamburger, Dobbin, Camac, Gwyn, Emerson and Young. It contains 776 pages, large octavo, with illustrations. It gives an analysis and study of the cases of Typhoid Fever in The Johns Hopkins Hospital for the past ten years.

The price is $5.00 per copy. Only a few copies of the volume are on sale. Those wishing to purchase should address their orders to the Johns Hopkins Press, Baltimore, M.\rtland.


The Johns HnpMns Hngyntnl BuUetiiw arc Ufucd mmithlv- They arc priiiffd liy THE FRIEDENWALD CO.. BaltiniMc. SiJigJe cctpiat may he procvred from Messrs. CVSUI^'0 <t CO. and the BALTIMORE NEWS CO.. Baltimnre. Subscriptions, $1,00 a year, may be addressed to the publishers. THE JCHNS BUPKIKS PRESS, BALTIMORE ; tingle copies uill be senl by mail f(»- fifteen cents each.


BULLETH^^^^^^


OF




THE JOHNS HOPKINS



HAL


Vol. Xll.-Nos. 121-122-123.


BALTIMORE, APRIL-MAY-JUNE, 1901.


Contents - April-May-June

  • On the Study of Anutomy. By Lewellts F. Bakker, M. B., . .
  • On tlic Occurrence of Tails in Man, with a Description of the Case Reported bv Dr. Watson. By Ross Gr.\nvii.i.e Harhlson, Ph.D., M. D., . '. "
  • Dcvelopinent of the Fist's Intestine. By Jons BurcE MacCallum, M. D.,
  • Bilateral Relations of the Cerebral Cortex. By K. Limion Mellus, M. D.,
  • A New Carbon-Dioxide Freezing- Microtome. By Cuari,e.s Russell Bardeen, M. D.,
  • Notes on Cervical Ribs. By Clinton E. Brush, Jr.,
  • On the Preservation of Anatomical Material in America by Means of Cold Storage. By Abkam T. Kerr, B. S., M. D.,
  • On the Development of the Nuclei Pontis during the Second and Third Months of Embryonic Life. By Margaret Long,
  • The Architecture of the Gall Bladder. Bv Mervin T. Si'dler, PlI. D., M. D., ."
  • Remarkable Cases of Hereditary Anchyloses, or Absence of Various Phalangeal Joints with Defects of the Little and Ring Fingers. By George Walker, M. D.,
  • Note on the Basement Membranes of the Tubules of the Kidney. By Franklin P. Mall,

Template:Ref-Mall1901 Mall FP. Note on the basement membranes of the tubules of the kidney. (1901) Johns Hopkins Hospital Bulletin 12:

  • A Comparative Study of the Development of the Generative Tract in Termites. By H. McE. Knoweh, Ph.D
  • A Composite Study of the Axillary Artery in Man. By J. M. IIitzuot,
  • On the Origin of the Lymphatics in the Liver. Bv Franklin P. Mall, = 140
  • Bern's Method of Reconstruction by Means of Wax Plates as Used in the Anatomical Laboratory of the Johns Hopkins University. By Charles Russell Bardeen, M. D., 148
  • Model of the Nucleus Dentatus of the Cerebellum and its Accessory Nuclei. By Harry A. Fowler, ISl
  • Use of the Material of the Dissecting Room for Scientific Purposes. By Charles Russell Bardeen, M. I)., 1.55
  • On the Development of the Human Diaphragm. By Franklin P. Mall, 158
  • Observations on the Pectoralis Major Muscle in Man. By Wauren Harmon Lewis, M D., 173
  • On the Blood-Vessels of the Human Lymphatic Gland. By W. J. Calvert, M. D., U. S. A., . . .'. . . , .177
  • Normal Menstruation and Some of the Factors Modifying It. By Clelia Duel MosHER, A. M., M. D., 178
  • Kctrojcction of Bile into the Pancreas, a Cause of Acute Hemorrhagic Pancreatitis. By W. S. Halsted, M. D., 170
  • The Etiology of Acute Hemorrhagic Pancreatitis. By Eugene L. Opie, m". D., 182
  • The John W. Garrett International Fellowship, 188

Notes on New Books, ISO

Books Received, 101


ON THE STUDY OF ANATOMY.'


By Lewellts F. Barker, M. B., Tor. Professor of Anatomy, University of Chicago.


With tlio advent of October, with its cool and bracing days and restful nights, there is regularly a quickening of activities in academic circles. The occupant of a [irofcssional chair, reinvigorated by temporary sojourn in forest or field, at the seaside or in the hills, resumes his teaching with renewed enthusiasm, and engages again in that original investigation which represents the most absorbing interest of his life. The


' An address delivered before the Faculty and students of Hush Medical College, October .5, 1000.


student, too, perhaps, as yet less conscious of the actual need of an occasional remittance from his labors, has nevertheless liad his holiday, and returns to the college of his clioice ready for another season of diligent application and eager to begin once more the arduous tasks which the pursuit of knowledge entails.

It has long been customary in colleges in which medicine is taught to call a meeting of tlie faculty and students at the beginning of the autumn session. Such a meeting permits of the reunion of former teachers and students and the intro


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[Nos. 121-122-133.


diiction and welcoming of new teachers and new students. It gives, further, opportunity for the making of certain special remarks; and I have noticed that there is almost universally a tendency on the part of the faculty to grant the privilege of remark-making to some memher of it who has lately been added to the staff. Being myself one of the most recent additions to an already large staff-family, the privilege has this year been gracefully allotted to me. However great a sacrifice on the part of my colleagues this may represent, I can assure you that the new-comer on this occasion, like the distinguished memher of the faculty who last year addressed you, considers it a great favor to have the opportunity of expressing the pleasure he has in coming among you and being counted one of you, and to meet with an occasion on which he can more or less generally indicate the aims and scope of the science which he represents, and so publicly justify the position which he holds. Fortunately. in this latter respect the task is an easy one, for anatomy has in medicine long ago won its place as a science essential as a basis for all the subsequent medical studies, and moreover, my predecessors in office have been men of such sterling merit, power and inspiration, that the subject is here appreciated and reverenced. Especially true is this of him who has immediately preceded me as the occupant of the chair, and who has left it in order to accept a chair in surgery; while we commiserate anatomy on losing so able a representative, we must congratulate surgery on the enlistment in its service of so well trained and enthusiastic an anatomist. He has at this college developed, among other things, a course in surgical anatomy — easily one of the best given in America — and this part of the anatomical work, I am glad to assure you, he has promised, for the present at least, to retain. You join with me I know in wishing my colleague, Professor Bcvan, a continuation of that success which he has already attained in the field of his ultimate choice.

The year in which we live marks an important epoch in the history of the college. Of a whole series of advances, I wish to call attention especially to one. Beginning with this autumn quarter, a closer relationship than has ever before existed between Rush Medical College and the University of Chicago has been established. Not entirely satisfied — for what true lover long is? — with that "sisterly" relationship which the term " affiliation " represents, the college has this year appointed to two of its fundamental chairs — physiology and anatomy — men who are already the occupants of chairs in the same sciences at the university. That such closer bond of union cannot fail to be of the greatest value, both for Rush Medical College and for the University of Chicago. I confidently believe. That it is only the forerunner of a still deeper intimacy, many, I am sure, both in the university and the college, fondly hope.

On thinking over anatomical subjects in the search for material for this address, the ideas which came to me grouped themselves in the main under two headings: (1) Wiat does the science of anatomy include? and (2) How can the study of anatomy best be prosecuted? Each of these headings cor


responds to matter enough for a single occasion; I have, therefore, decided to spend the time at my disposal this evening in a consideration of the former of the two questions, and to reserve for another time and place what I have gathered in answer to the latter.

Of the whole group of the natural sciences, there is perhaps no other member, the jirovince of which is less well understood by the general public than is the science of anatomy. As ordinarily thought of by the layman, it is a science the study of which necessarily precedes the practical work of medicine and surgery; a science which is largely, if not wholly, descriptive, and one which to be mastered requires prolonged oeciipation, scalpel in hand and pipe in mouth, with dead and partially decomposed human beings. Such a view of the science, though perhaps not surprising when we recall the methods by which anatomy — so-called — has frequently in this and other countries been prosecuted, could, I do not need to tell you, be scarcely more widely removed from the truth. Anatomy is not simply a descriptive science; the study of it as a preparation for practical medicine and surgery represents only one side of its interest and usefulness; the scalpel is now perhaps the coarsest instrument it employs; its work is by no means confined to the human body alone, much less to the dead human body, and when it does deal with the latter, the material can be so well preserved that even the fragrant Havana is said to be more offensive to some sensitive souls than are the odors from the well kept preparation room.

Even medical men differ markedly in their conception of what anatomy includes, their ideas being based largely upon the kind of anatomy they theniselves were taught, and upon the anatomical needs of the particular branch of medicine which, after graduation, they have cultivated.

Nor is there uniformity of opinion among the pure anatomists themselves, as can be readily seen by a perusal of the various addresses made by scientific anatomists in different parts of the world during the last twenty years. A free expression of opinion upon the subject has, however, gone far .to make the aims and scope of the science clearer, until at present its principal representatives are more nearly in accord with regard to them than ever before.

In what this accordance consists, I can, I believe, make clearest to you by glancing briefly at the various steps through which the science has passed from the period when the earliest anatomical observations were recorded to the present day.*


- In the preparation of tliis address I have made free use of a large number of addresses made on similar occasions by other anatomists. I have had no hesitation in borrowing liberally as will be immediately apparent to those who are familiar with the bibliography. Especially useful to me have been the addresses and papers of His, Hertwig, von Kolliker, Macalister, Mall and Waldeyer. The following are some of the sources consulted :

Baker, F.: The rational method of teaching anatomy. Med. Rec, N. T., 1884, sxv, 431-43.5.

Bevan, A. D.: What ground should be covered in the anatomical course in American medical colleges ? And what part of this ground


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89


There can be no doubt that from the earliest times, curiosity concerning and interest in the make-up of the human body has existed. The references to man's body and its organization frequently to be met with in the pages of the old Hindu Vedas and of the earliest writings of all the Oriental nations make this evident. Nevertheless, the awe in which men stood before the human cadaver, together with the penalties threatened by religious leaders for its molestation appear to have effectually prevented any systematic examinations and the little knowledge possessed by the ancients, aside from the conclusions drawn from animals killed for food or for sacrifice, seems to have been drawn from the instances in which, through the violence of war, the chase, or of the natural elements, the human body became dismembered or eviscerated.

The earliest dissections of the human body of which no doubt exists are those which were undertaken at the Alexandrian School (B. C.) by Herophilus and Erasistratus, supported and protected by the intelligent Ptolemaic rulers. The name of Herophilus is still familiar to every beginner of anatomical studies in tlie* term Torcular Herophili. The statement is made, though I hope it is not true, that these daring anatomists went so far, with Ptolemy's sanction, as


should be covered in the first year? What in the second year? Proc. Ass. Am. Anat., Wash,, l.S'.)4, vi, 47-40.

Brown, .1. J[.: Tlie science of human anatomy ; its history and development. Edinb. M. J., 1SS4-5, x.xx, 58.5-596.

lirownina;, W. W.: Remarks on the teachins;; of practical anatomy. Brooklyn M. ,]., 1894, viii, 329-341.

Budge, J.: Die Auftrabeu der anatoraischen Wisseuschaft. Deutsche Rev., 1882.

Cleland, J.: Lecture on anatomy as a science and in relation to mctlical study. Lancet, Lond., 1892, ii, 93S, 982.

Cooke, T.: The teaching of anatomy ; its aims and methods. Lancet, Lond., 1893, ii, 1153, 13.^)0.

Cuuniugham, D. J.: Bologna; the part which it has played in the history of anatomy; its octo-centenary celebration. Dublin. J. M. Sc, 1888, 3 s., .x.x.xvi, 4li5-484.

Debierre, C: L'Anatomic, son passc, son importance et son role dans les sciences biologiques. Rev. Sclent., Par., 1883, 3 s., xv, 68-74.

Duval, M.: L'Auatomie guucrale et son histoire. Rev. Sclent., Par., 1886, xxxvii, 65-107.

Dwight, T. : The scope and the teaching of human anatomy. Boston M. and 8. J., 1890, cxxiii, 337-340; also, methods of teaching anatomy at the Harvard .Medical School : especially corrosion preparations. Boston M. and S. J., 1891, cxxiv, 47.5-477.

Flower, W. U.: An address delivered at the opening of the section of anatomy. Tr. Interuat. M. Congr., Loud., 1881, i, 133-144.

Gegenbaur, C: Ontogenie und Anatomie iu ihrcn Wechselhezi'lchungen betraehtet. Morphol. Jahrb., Leipz., 1899, xv, 1-9.

Ilertwig, O.: Der auatomische Unterricht, Jena, 1881.

llartwell, E. M.: The study of human anatomy, historically and legally considered. Johns Hopkins Univ. Stud. biol. lab., Balto., 1881-2, ii, 65, lie,.'

His, W.: Ueber die Aufgabcn und Zielpunkte der wissenscliaftlichcn Anatomie. 'Leipzig, 1873.

His, W.: L^eber die Bedeutung der Entwickelungsgeschichtc fiir die Aufl'assung der organisehen Natur. Leipzig, 1870.

Humphry, G. M.: An address on the study of human anatomy. Brit. M. J., Lond., 188T, i, 1030.


to dissect living criminals, from which Tertullian designated Herophilus as laiiius (Fleischer).

This opportunity for the anatomical investigation of the human body appears to have been unique, and it continued only for a short time. Even Galen's studies, the results of which were held for the following ten centuries at least to be infallible, were limited to the bodies of animals; he recommended, it may be remembered, the study of the bodies of apes and swine — the animals which in his opinion were nearest to human beings. After Galen, the natural horror which the examination of the dead body excites, together with the edicts of the church against dissection, prevented any further progress of descriptive human anatomy for a very long period. The church declared that Galen had been infallible, and that therefore no further anatomical studies were necessary. Fortunately for science, which knows but little infallibility, certain of its votaries in liigh favor at Eome gained permission, in the fourteenth century, to make dissections of human bodies, and to use them for demonstration before students. Mondini in Bologna again opened the path for scientific anatomical inquiry and started in Italy a movement which placed that country, as far as medicine is concerned, in the lead. Students from distant lands were at


Kollikcr, von A.: Die .Vufgiihen der anatomischen Institute, Wiirzburg, 1884.

Krause, W.: Die Methode in der Anatomie. Internal. Monatschr. f. Anat. u. Histol., Berl., 1884, i.

Keiller, W.: The teaching of anatomy. N. York M. J., 1894, ix, 289, 513, .545.

Keen, W. W.: A sketch of the early history of practical anatomy. Philadelphia, 1870.

Macalister, A.: Introducing lecture on the province of anatomy. Brit. M. J., Lond., 1S83, ii, 808-811.

Mall, F. P.: The anatomical course and laboratory in the Johns Hopkins Medical School. Johns Hopkins Hospital Bulletin, 1896.

Meyer, von H.: Stellungund Aufgabeder Anatomie in der Gcgenwart. Biol. Centralbl., 1883.

Marks, G. IT.: The study of anatomy; its position in medical education in England and in America. Boston M. and S. J., 1885, cxiii, 104107.

Morris, 11.: An address on the study of anatomy. Brit. M. J., Lond., 1895, ii, 1337.

Pepper, W.: Introductory remarks at the ojiening of the Wistar Institute of anatomy and biology. Univ. iM. Mag., Phfla., 1893-4, vi, 569-572.

Robinson, B.: A plea lor the more thorough study of visceral anatomy. (Jalllard's M. J., N. Y., 1894, ix, 289-296.

Schiell'erdecker, P.: Der auatomische Unterricht. Deutsche Med. Wehnschr., Berl., 1882, viii, 46.5-467.

Shiels, G. F-: A plea for the proper teaching of anatomy. J. .Am. Med. Assoc, Chicago, 1894, xxiiii, 110-112.

Testut : Qu'est-ce que I'homme pour un anatomiste ? Rev. Scicnt., Par., 1887, 3 s., xiii, 6.5-77.

Turner, W.: Address at the opening of the anatomical department in the new buildings of the University of Edinburgh. Lancet, London, 1880, ii, 724, 759.

Virchow, R.: Morgagni und der auatomische Gedanke. Bcrl. Kl. Wehnschr., 1894, xx.xi, 34.5-350.

Walton, G. L.: The study of anatomy in the Leipzig University. Boston M. and S. J., 1883, cvi, 389.

Waldeyer, W.: Wiesoll man Anatomie lehren und lerneu. Berlin, 1884.


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[Nos. 121-122-123.


tracted, as tliey always have been and always will be, to tlie point where progress was making the greatest headway.

The great Vesalivas, often known as the father of anatomy, was among these wandering scientists. Born in Belgium and edneated in France, he prosecuted his anatomical studies in Italy, especially when professor at Padua, to such a degree that he merits a place among the world's greatest reformers. This energetic, truth-seeking, idol-breaking, authority-denying man, dared to look at things as he saw them rather than as Galen had said that they should be, and thus made discoveries of the first importance in anatomy; by his artistio powers he rendered many of tliem imperishable; best of all, lie broke forever the tyranny of tradition in anatomical knowledge, and threw wide open the gate by which men must always enter in the pursuit of anatomical truth. Vesalius was a contemporary of Liither; the year of his death is that of the birth of Galileo and of Shakespeare.

It was the spirit which animated Vesalius which later led William Harvey, the founder of physiology, to the discovery of the circulation of the blood, and Giovanni Battista Morgagni, the founder of pathology, to that mode of conception which Virchow has designated " the anatomical idea in medicine." It is the spirit which is embodied in every scientific worker of to-day who accepts the records of past investigation only as a guide — a guide which must be fallible since it is human — and which, therefore, must be repeatedly controlled; a guide which needs constant revision on account of the ever-increasing extension of the domain of sense, and ime, which, if not added to significantly by the scientist in his lifetime, will stand as an everlasting witness to his inefficiency, a perpetual testimony to his lack of consequence.

Like all the natural sciences, anatomy in its earlier stages consists, of necessity, in the amassing in an empirical way of a store of naked facts. In other words, the subject is purely descriptive until a suflBcient number of facts have been collected to make their arrangement and classification a task worth while. Adequate descriptions are based upon intelligent ohscrvatioti, which in turn is dependent upon the skillful use of the organs of sense, including the means which modern technique is ever inventing to extend them. The body is e.xamined externally and internally in its various parts; it is looked at; it is felt. The size, shape, color, weight, consistence and reciprocal relations of the parts are noted; the results are recorded, the attempt being made to establish thd material content of the science with all possible certainty, sharpness and clearness. The parts have first to be distinguished and named; then accurately described, their physical characters being established in language. The description of a natural object that shall call up in the mind of the reader a precise image of the object and that shall serve as a reliable guide to a succeeding observer, does not fall within the province of every man's capacity; happy indeed is the anatomist who possesses the power, for as has more than once been pointed out, an exact and clear description of the known is often of as great value as the so-called " discovery " in the region of the unknown.


The satisfactory naming of the various parts alone is a task of far greater difficulty than at first appears. An object must be studied for a long time, in many coimtries, and by men who know the relations of anatomy to every subject with which that science is allied, before a name for a part which shall be in accord with all the requirements can be decided upon. Almost every part has at various times received a series of names; periodical revisions of nomenclature by representative committees are accordingly desirable in order to arrive at uniformity among anatomists and to relieve the science of an immense niimber of names, since at best it must be grievously burdened.

Ever since the time of Vesalius there has been an unbroken series of anatomical observers who have devoted their powei's to the attaining of skill in dissection and anatomical description. With energy and endurance and often at great personal sacrifice, this band of anatomists has developed this side of our science until it has reached the degree of precision which characterizes it to-day; a state indeed which many believe to be practically complete and incapable of further progress. Of the difficulties overcome by Americans in helping with this work since Mr. Giles Firman made the " first anatomy of the country," a good idea can be gained from the admirable historical review which we owe to E. M. Hartwell. While it is obvious that there must be a temporal limit to the discoveriea which the naked eye is to make in anatomical fields, one has nevertheless only to refer to the current journals to see that the limit has not yet been reached. But the limits of progress in anatomical description will by no means be synchronous with those of macroscopic discovery of the objects themselves, indeed, considering the complexity of man's architecture and the different and ever-varying view-points whence descriptions are being written, it is scarcely conceivable that man will ever attain to descriptions which will be satisfactorily final. To the surgeon, to the artist, to the physiologist, to the scientific anatomist, the details of parts are of utterly different significance; the varying scale of anatomical values requires in each case a special description; an objective characterization of all details, merely as such, would make anatomical descriptions so ponderous and chaotic as to render them totally useless to any one. Nor can anatomical illustrations, in colors and otherwise, which are perhaps even more valuable than anatomical descriptions, ever be completely objective. The exact plates of anatomical objects which approach of late years ever nearer to that degree of accuracy which will permit of the taking from them of mathematical measurements, never attain actually to perfection; there must always be an element of subjectivity in them which may be inconsonant with the needs of some other observer at some other time.

Again, the greater or less degree of variability to which all parts of the animal body are subject, makes it difficult for anatomists to agree as to what shall be called normal, and thus the same object has frequently to be described in several different ways and multiply and exactly represented in pictures. There thus remains and ever will remain a task for


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the anatomist in the domain of anatomical description and of anatomical illnstration.

If it be true that in the fields just referred to there is still much work to be done, the statement is all the more justified with regard to the taking of measurements and weights of the body and its jjarts. The shape of the natural objects is nearly always such that the localization of fixed points whence measurements can be taken is rendered very difficult — so difficult that frequently the comparison of the measurements of one observer of an object with those of another observer of the same are useless. Again, owing to. the variability of the bodily dimensions in the two sexes, in different races, at the various ages of life, according to individuality or under different physiological conditions, nnless a whole series of data accompany a given measiu'ement, the result may be of no value to a succeeding observer. In modern anthropology, however, definite criteria are always attended to and tlie measuring metliod is proving to be of the highest service in the elucidation of the questions that science has to solve.

The difficulties of anatomical measurement in large part obtain also when the weighing of anatomical objects is imdertaken. Notable results have already been obtained, however, not the least of those in connection with the central nervous system being gained through the comparatively recent work of my colleague. Dr. Donaldson, in the university. The application of the method to the determination of the normal by Thoma may also be referred to as the beginning of a long series of investigations which, in the end can scarcely fail to be of the greatest importance. As liis, who has discussed this and the foregoing subjects in an admirable manner, points out, it is difficult to imagine how the study of variations in constitution is to be approached unless this and similar methods are employed. As he says, it must be of decisive influence for the physiological capability of an individual, whether in his organization the musculature predominates over his nervous system, his epithelial tissues or his glandular organs, whether his heart is relatively large or small, whether accordingly it can increase the average blood pressure in the arteries to a great or to a slight degree, whether the man has a large or a small liver or whether ho has a long or short alimentary canal. The study of anatomy with the unaided sense-organs is, as we have seen, one of no small magnitude, and one not yet completed. What then is to be said of that descriptive anatomy which invades the territory in whicli the eye only with the aid of the microscope can penetrate? The field of the microscopic anatomist is at least a thousand times wider than that of the macroscopic worker, and in that field, what has been said above concerning description, pictorial representation and anatomical measurement, equally holds good. It will yet be long ore the collection of microscopic data will have been completed. New methods open up new problems, and at present progress, descriptive and microscopic anatomy may probably occupy workers for centuries to come. Even with the methods and microscopes now at our disposal, we have entered a museum. the largest part of whicli has yet to be accurately catalogued,


and who can say what new doors the methods and the microscopes of the century just before us are about to open vip? The science of histography is almost as undeveloped as was geography before the voyage of Columbus. Between the histographic world of to-day and the arcbitectural world of stereochemistry who will dare to prophesy what rich territories may exist?

The mere observation and registration of naked facts does not, however, satisfy for long the cravings of the investigating human intelligence. Indeed, there is something of a blunting character about the process if long continued without the synchronous operation of other faculties of the intellect. Man is a classifying and generalizing animal; there lies deep in his nature a desire to arrange the facts he observes in an orderly manner, with the object of understanding them. It is in the attempt to satisfy this human tendency that anatomy, instead of remaining a purely descriptive science, becomes elevated to a plane on a level with the other inductive sciences.

Evidences of attempts at anatomical classification are found among the earliest anatomists. The close resemblance of certain parts of one another soon gave rise to the idea of organic systems; such as the muscular system and the nervous system. The keen observations of Aristotle on the paries similares and the partes dissimilares may be recalled, as well as those of Fallopius outlined in his Tradatus quinque de partibus similaribus. It was left to the organizing brain oi the yoimg Frenchman, F. Xavier Bichat, to get a grasp for the first time of the relations of elementary tissjies to tho general architecture of the body. Although, through overwork and impecuniositj', his penetrating eyes were forever closed at the early age of about 30 years, Bichat left behind him three treatises — his " Traite des Membranes," liis " Eecherches physiologiques sur la vie et la mort," and his " Anatomic generale " — a legacy so immense that we cannot help lamenting with wondering regret the too early arrest of his labors. He recognized the fact that whereas in chemistry the more complex bodies are composed of simple elements, so in the architecture of man's body, simple tissues are variously combined to form the complex mixture of tissues which are ordinarily known as organs. He distinguished some 21 systems or tissues — the cellular, the osseous, the fibrous, the cartilaginous, the nervous, the muscular, the medullary, etc., basing his classification on the manner in which each tissue behaves in the presence of various reagents, the physical and vital properties of each and, finally, the character of each when met with under diseased conditions. In other words, Bichat was the founder of the modern science of histology, or, as it is sometimes designated, " General Anatomy." '

Before following the progress of anatomy further along this line, a word must be said concerning what must be regarded perhaps as the first direction taken by the investigat


'Cf. Duval, M.: L'Aiiatomie generale et son liisloiro. Rev. Scient. Paris, 1886, xxxvii, 05, 107.


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ing mind toward the understanding of organic forms — namely, the pli3'siological (in its first stages, the purely teleological). As has long since been pointed out, the language of anatomy is sufficient evidence of the long existence of the teleological conception in this science. For thousands of years the individual parts of the body have been known as " organs," and the processes going on in them as " functions." Just as function was unthinkable without a corresponding organ, so an organ without function was inconceivable, and thus wherever, in the series of well-understood parts of the body, one remains over whose purposeful participation in the processes of life is not understood, towards this is directed over and over again the mental acumen of the investigator to assign to the reluctant organ a definite significance.* It is not my purpose here to enter into a discussion of teleology. The world has been widely enough explored to utterly dispose of that gross anthropomorphic form of teleology which pointed to a humanly scheming architect of the universe, and whether or not we accept some more correct form of teleology is, at present, matter for individual opinion. This much is certain, that while no teleological view of nature actually explains the organization of a human body, the teleological conception has been particularly heuristic in its effects in the investigation of the relation between the physical processes in, and the physical characters of, the various parts of the body. Ever since Galen, though animated by a false teleology, wrote his De usu partium, in which the size, position, number, consistence and structure of the various parts are treated as facts which can be understood only through the investigation of the purposes which they subserve, this mode of consideration has been among the most influential. Even to-day a large part of the profitable research undertaken by anatomists, physiologists and pathologists, has for its aim tho elucidation of the relation of structure to function, especially in microscopic domains. The work done in Ludwig's laboratory was largely of this nature, and as recently as 1883, H. v. Meyer" has asserted that the only possible way of understanding the organs is to proceed to the study of them froii) the physiological view-point. But if this were true, then all scientific anatomy would be physiology, a statement which narrow-minded physiologists might applaud, but whirli broader men know to be untrue. Physiology is one of tho daughters of anatomy, and is not likely so soon to forget the fifth commandment. Johannes Miiller was the last great scientist who covered both fields of anatomy and physiology; since his time investigators have cultivated one of (lie two at the expense of the other, a division of labor which we must recognize on the whole as beneficial, though that it is accompanied by certain drawbacks must also be confessed. Especially difficult is it to sharply separate the study of strueturo from that of function in the science of cytology, founded by Schleiden and Schwann, pupils of Johannes Miiller in the


Cf. His, W.: Ueber die Bedeutuna; tier Entwickehingseeschiclite fiir die Auffassiing dcr Organiscbe. Natiir. Leipzig, 1870.

>■ V. Meyer, IT.: Stellnno' und Aiifgabe der Anatomie iu der Gegenwart. Biol. Ceutralbl., 188.3, No. 12.


fourth decade of this century. The development of the celldoctrine, modified as it was somewhat later by the introduction of the protoplasm-theory by Max Scliultze, marks a most important epoch in the history of both anatomy and physiology. Its value for the more practical side of medicine is sufficiently in evidence when one of its direct outgrowths, the cellular pathology of Eudolph Virchow, is recalled. The appalling elaboration of technical methods during the last few years has led to the accumulation of cytographic data which remove all the comfort we once had in looking upon the cells as elementary structures. Though cytophysiology is as yet far behind cytography in its state of development, there no longer remains any doubt that in approaching the cell we stand before an organism of enormous complexity of constitution, endowed with functional activities which must for long remain to us unfatliomable. Any one who has worked much with protoplasm and nucleus, with archiplasm and centrosome, with cell-fibrils and cell-granules under various physiological conditions, cannot fail to appreciate the fact that here only the threshold of inquiry has been crossed — the exploration of the real nature of the cell only just begun. Indeed the evidence is fast accumulating in favor of the opinion that many of these morphonuclcar cell constituents represent precipitates due to the action of reagents, and the laws governing their regular appearance under definite conditions are being investigated. It is exactly in these studies that structural and functional investigation still do well to go hand in hand, a fact which a survey of the cytoliigical handbooks, now becoming so nunioroiis, will show, is meeting with general recognition. I believe it was Du Bois Reymoud who ventured the statement that " an ocean steamer with all its machinery and intricacies of construction is far less complicated in its composition than a cell." Would that the cell were no more complicated than the ocean steamer in construction! — the modern investigator would then soon be ready witli the solution of its problems. Alas! the difficulties are not confined to the study of these organisms as individuals; already we have entered upon the investigation of their social relations, and cell-altruism and cell-egoism, cellstates and revolutionary cells are discussed as actively among cytologists as are the similar social questions concerning organic individuals of another order by the people at large. Further, in cytophysics and cytochemistry, research is at present most active — these subjects representing one of the most interesting subdivisions of recent physiology. Should the gulf between the present microscopic picture of the cell and its chemical structure ever be bridged, stereochemistry would enter into the domain of anatomy. So much in general, with regard to the physiological view-point in anatomy. Closely allied to the foregoing, and in reality an offshoot from it, is the mode of consideration of the surgical and topographical anatomist. In this branch, the- individual regions and cavities of the body are dealt with Avitb regard to the reciprocal position of the various organs and systems. Surgical anatomy studies these relations only in so far as they are of importance in operative procedures; topographical an


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atomy, a wider subject, studies tlie relations mentioned and independently of their significance to the surgeon. The various regions of the body are studied sometimes in layers, sometimes with regard to serial clues to a particular structure. Sections of frozen cadavers have here proved to be of great value for the study of relations and for helping the student to make mental reconstructions of the parts analyzed by dissection. Surgical and topographical anatomy are thus seen to be subjects of very high practical importance — the former especially for the surgeon, the latter also for the worker in internal medicine. It is this kind of anatomy Which has been brought to so high a state of cultivation in Great Britain, and especially in London, where most of the anatomy has been taught by men in surgical practice. Valuable as such instruction is for furgery and medicine, it should not be forgotten that it is applied anatomy rather than anatomy proper, and no less a scientist than Macalister has deplored the lack of advances in anatomy in England, attributing it largely to the one-sided mode of instruction in vogue, and to the examinations, to the passing of which the teaching is in large part directed. Surely certain morphological considerations are as important for the student of anatom.y as the learning by heart of the various relations of an artery, especially if the student is not to become a surgeon; it would be melancholy indeed if there were not at least some members of the anatomical classes who regard the study of the architecture of the brain and spinal cord as interesting and as important as that of the perineum.

But anatomy as a science would never have attained to the dignified position it now holds had the minds engaged with it remained satisfied, after observing and registering its material content, with attempting the explanation of the human body from the physiological view-point or by exliausting the possibilities of its relation to the surgeon's knife.

As in the other natural sciences, the causality-need of the intelligence has forced the anatomist to undertake the investigation of the origin of the organic forms which he studies, and of the relations of these forms to other similar and dissimilar organic forms accessible to examination. In other words, the comparative and the genetic methods of study have been resorted to. Comparative anatomy and embryology together constitute morphology, at least in the senso in which the term is ordinarily used, and in morphology we recognize the part of anatomy which makes it truly worthy of being designated a science.

In the application of the comparative method, not only are the different parts of the human body compared with one another — the arms with the legs, the brain with the spinal cord, the skull with the vertebral column, the various segments and segmental partitions with one another — but man, recognized as a member of a long series of animals, is compared with each of them in turn, and they with one another, with the object of establishing groups of type forms and of learning the plan of architecture, not only of the single creature, but also of the whole series. At first, anatomists studied the forma which to them seemed to resemble man most closely, but the


gradual transition from one form to another was so striking that animal after animal was studied until finally the whole world of organisms has been submitted to the examination of the comparative investigator. Oken and Goethe, Cuvier, Meckel, Geofl'roy, St. Hilaire, Lamarck, Wallace, Darwin, Haeckel, Huxley, Gegenbaur and Leidy are names which have become very familiar to us in this field. The world of living creatures is a unitary system, of which man is an inseparable portion. First, when the whole system has been worked through do the form and significance of many of man's parts become intelligible. The animal series can be thought of as a tree with the simplest forms at the root, the trunk branching at its origin, each branch in turn subdividing into limbs and twigs until the highest degree of differentiation is reached. It is this recognition of the lawful relation of organisms to one another which the study of comparative anatomy has afforded us. Such a recognition, now general, was little less than startling to those who first arrived at it. That it pointed to some more general law was obvious. As Goethe himself, no mean participator in comparative studies, beautifully expressed it:

" Alle Gestalten sind ahnlich und Keine gleicbet der anderm, Und so deutet das chor auf ein gelieimes Gesetz."

Has this secret law been discovered? Many believe so and look upon Darwin's doctrine of descent as a generalization worthy, on account of its scientific value, of being placed side by side with Newton's theory of gravitation. Whether the evolutionary doctrine be unequivocally accepted or not, certain it is that the relationship of forms which comparative anatomy reveals, finds in this genealogical conception of Darwin a more satisfactory explanation than any other hitherto offered.

Closely allied to the phylogenetie mode of consideration is that \\hich we designate as the embryological ontogenetic or developmental. In the human species, as in every other, the life of the individual member is of short duration; each human organism has a beginning, a period of growth and development, followed, even in the life of maximum length. in the course -of a few decades, by decline and death. Generation follows generation as wave follows wave on the surface of a ruffied sea. In the transference of life from one generation to another the material substratum sinks to a minimal amount — the new human being begins as a fertilized egg-cell 1-120 of an inch in diameter, weighing only a minute fraction of a gramme. From this simplest of beginnings it gradually passes through a long series of developmental stages, the character of these stages varying somewhat under environmental influences, each .stage being the nnecessary consequent of a preceding stage, and at the same time the necessary antecedent of the stage which follows it until finally the organism attains to the fullness of differentiation of which, under the circumstances of its environment, it is capable.

In this long series of developmental stages which every mammal passes through, the earliest are very, very simple and correspond in form closely with the lower forms in the animal kingdom. But as cell-division in the embryo proceeds, the


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shaping of tlie organism becomes more complex, resembling higher and higher forms of animal life, nntil finally that of mammals is assumed. Even at this period the nnskilled observer might easily be confused if he were required at a glance to distinguish a human embryo from those of several other mammals at a similar period of development. Ultimately, the differential characters of the species become clearly marked, and even the tyro can easily recognize them Tiio more skilled the observer, however, the earlier in the development will the species-criteria be decisive.

Comparative embryology becomes all the more astonishing a study when we realize that the embryological history of every higher animal is, for a long period at least, almost identical with that of a whole series of allied forms. No wonder, then, this state of things being acknowledged, that the embryologists, like the comparative anatomists, have pictured the genetic relations of the different animal forms also as a tree, a tree which on close examination is found to accord very closely with the tree of relationship constructed by the comparative anatomists.

Comparative anatomy and embryology are, therefore, closely interwoven subjects, and each may, in a way, be looked upon as a control for the other, though each has its special problems, and each sets about the solution of these in a manner peculiar to itself. Take, for example, the attempts at an explanation of the series of forms through which the individual passes in its development. Many comparative anatomists, accepting Darwin's doctrine of the origin of species through a struggle for existence among generations influenced by heredity and variation, would explain the development of tlie individual member of a species as a temporarily compressed recapitulation of the developmental course of the species as a whole. While this doctrine that " ontogeny repeats phylogeny" has been maintained by eminent scientists there are others who are unwilling to accept what cannot bo proved; and some of the embryologists especially feel it their province to attempt to explain from embryological studies alone, and without reference to phylogenetic history, the origin of the various form-stages through which the individual passes. Already great strides have been made in the direction mentioned, especially through the investigation of the laws of growth; and the field of developmental mechanics, though so lately entered upon, has proven to be one of the most fruitful of those thus far tilled. One of the foremost investigators along these lines goes so far as to assert that the growth of every organic germ must, as a process strictly regulated according to time and space, possess a mathematical expression in which the velocity of growth of each point is determined in its dependence on the time and the position. Whether such formulaa will ever be set up and the kingdom of organic forms thus subordinated to the domination of simple numbers, seems doubtful, but in any case the conception is an interesting one. We need not, however, look into the nebulous distance for the advantages to accrue from developmental study. Fear at hand are thousands of facts of the greatest importance for anatomy as a whole and for


the practical branches of medicine and suvgei'y to be gained only through this method of study. Scarcely a part of the body but what is now better understood than was otherwise possible. I need only mention the remarkably complicated morphology of the brain and the sense organs, the distribution of the intestines, the grouping of the various voluntary muscles, the puzzling course followed by certain of the nerves and of the reproductive organs in the two sexes, to call to mind some of the features which embryology has gone far to illuminate.

I dare not pass by unnoticed here two phases of investigation which naturally follow upon the others, but which have only very recently begun to be extensively cultivated, viz.: those of histogenesis and of comparative histology. Histogenesis stands in the same relation to comparative histology as does embryology to comparative anatomy. Indeed, it is simply jDUshing the microscope into embryology and comparative anatomy, and is, in a way, comparable to the advance from gross descriptive anatomy to microscopic anatomy. By histogenesis we mean the study of the development of the individual tissues, including that of the individual cells (cytogenesis). By comparative histology and cytology we refer to the comparative microscopic study of the various tissues and cells through a series of animals. The light throuTi upon many of the unsolved problems of structure by these methods is unexpectedly brilliant, and the future has much to hope from it; MacCallum, too, has shown how important these methods can be in helping to explain certain pathological phenomena met with in heart-muscle, and there can be little doubt that we are on the brink of the discovery of a series of relations between histogenetic ccmditions and j)athological processes.

Lastly, as a crowning piece to the whole system of anatomical study, experimental morphology must be recognized. As but a child among the kindred sciences, it is of robust constitution, being the offspring of vigorous parents, and, in this country especially, in an environment most suitable for its healthy growth. The anatomist is no longer confined to the study of adult forms, or of forms in their natural mode of development; he can now, to a certain extent, artificially control form-production by resorting to the experimental method. The experiments which have been made upon heteromorphism, upon the artificial production of malformations, and upon the grafting of embryos, are full of interest, so much so as to disturb the equanimity of the soberest of scientists. During the last year or two we have been — I was going to say — shocked by the bringing of the proof by my colleague. Professor Loeb, that the eggs of several forms not naturally parthenogenetic can be fertilized — or at any rate, brought to development in the absence of spermatozoa, solely through the action of (?) physico-chemical influences. With miracles such as these already performed, we can but stand in awe of the work of the future.

Most sketchily and imperfectly 1 have tried to give yon an idea of what the study of anatomy includes, viz.: descriptive or systematic anatomy (gross and microscopic), physiological


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anatomy, surgical and topographical anatomy, histology or general anatomy, ineUiding histography and cytology, comparative anatomy, embryology, comparative histology and embryology, histogenesis and lastly experimental morphology. Assuredly the subject is wide. It is, I am sorry to say, too wide to be mastered in all its details even when a whole lifetime is devoted exclusively to it. The scientific anatomi;;!, after familiarizing himself with the main facts and principles of its various subdivisions, does best, in agreement with the great law of division of labor, to direct his efforts towards the acquisition and promulgation of knowledge in some one portion of it.

And now for a word of welcome to the class just entering upon the study of medicine. You have taken, gentlemen, the first direct step which is to lead you into one of the noblest professions in the world — into a profession in which your lives are to be consecrated to the service of suffering men and women. You have to learn the laws which govern hcallli and those which underlie disease. Yon, like your predecessors, will find that a large proportion of your time and .energy in life will be directed toward the prevention" of the occurrence of disease, rather than to the cure of it, for medical men have the proud distinction of being perhaps tlie only workmen " who make it their first duty to stop the sources of supply from which they derive their income." Hard work during the next four years will be required of every one oT you; indeed, your time will be so occupied and your mental powers so strenuously engaged that you will have but little opportunity for recreation or for the amenities of life. But while this is the most difB.cult period of your career as far as intellectual work is concerned, do not, I beg of you, forget altogether the man in the making of the physician or surgeon. However much your instructors may stimulate you, however much work they may ask you to do, you will be wise if you retain some period of the day, be it only half an hour or even less, when you can withdraw from men and medicine and in some quiet nook indulge a wholesome longing for good general literature. Keep your old friends by you — your Plato and Marcus Aurelius, your Emerson, Carlyle, your Dante, Shakespeare and Milton, your Goethe, Shelley and Keats. If your osteological studies prove refractory you may find the stoicism of Epictetus a remedy for your disturbed spirit; after the depressive influences of pathological anatomy the lyric of Goethe, the raptures of Shelley, or an essay of Stevenson may prove to be uplifting; to combat the intoxicating fumes of the chemical laboratory try the antidotal effects of Burton, of Sterne or of Eabelais. The time so spent will not only be revivifying for the moment, but will be of the greatest value to you in your professional life after graduation. Skill is more and more reverenced, but skill without culture has lost half its power. And culture, like reputation, has not only to be gained but to be kept, nor is it gained or kept without cfTort, without constant vigilance.


Permit me to hope that you have laid broad foundations in the sciences which arc fundamental for medicine; viz.: physics, chemistry and biology. Without thorough training in these it is impossible to keep abreast of the rapidly swelling tide of discovery in modern medicine. If, further, you are familiar with the French and German languages you will find it possible to become conversant with important new facts and discoveries months and sometimes years before they enter into the English text-books. Of the distinctly medical sciences, anatomy, physiology and physiological chemistry, together with pathology, form the framework upon which all the rest of the medical sciences are built. Failure to make this framework solid renders the superstructure inevitably unsafe. Do not forget that the medicine of to-day differs from that of the years close behind us chiefly in the substitution of "handcraft" for much of the former "redecraft." In these days, too, as it has well been put: The eye cannot say unto the head, I have no need of thee." Instead of accepting the statements of others about things as of yore the medical student is nowadays being made to do things. Instead of memorizing text-books, quiz compends and lecture notes, he is more and more required to study the natural objects, to observe accurately, to record concisely and adequately, to experiment intelligently. While good lectures, good recitations and good text-books still have their place, the student is wisely encouraged to interrogate Nature for himself and to believe in the replies he obtains from her rather than to put implicit confidence in the descriptions of others.

The new methods of medical education arc costly; they demand large laboratories, expensive equipment and scientifically trained instructors. They cannot be satisfactorily introduced into schools where the sole income is derived from the fees of students; large endowments are absolutely essential for the proper carrying out of the plan.

Finally, gentlemen, let me give expression to the hope that among this class now entering, besides the large number who will go on into beneficent and successful practice, there may be some who, willing to scorn delights, to live laborious days, will set before them the high hope of making actual additions to knowledge. It is not fair that we should accept the gifts of our forerunners without making the effort ourselves to enrich the general stock of knowledge. The paths of investigation are not smooth; the way of research is difficult. But the goal is strife-worthy, and the rewards are sufficient.

In closing then let me quote those stirring words of the sage of Chelsea, which I excerpt from his Sartor Eesartus.

"Produce! Produce! Were it but the pitifulest infinitesimal fraction of a Product, produce it in God's name! 'Tis the utmost thou hast in thee: out with it then. Up, up! Whatsoever thy hand findeth to do, do it with thy whole might. Work while it is called To-day, fur the night comctli, wherein no man can work! "


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ON THE OCCURRENCE OF TAILS IN MAN, WITH A DESCRIPTION OF THE CASE REPORTED

BY DR. WATSON.

By Eoss Granville Harrison, Ph. D., M. D., Associate Professor of Anatomy, Johns IIopMns University.


Some years ago Bartels' gave an excellent resume of onr knowledge and beliefs concerning the occurrence of caudal appendages in man, showing that references to this peculiarity are to be found as far back as the writings of Pliny and Pausanias. Appended to Bartels' paper is a map, which shows the various lands supposed at one time or other to have been the haunts of human races with tails. These regions include not only widely distant portions of South America, Asia and Africa.- but also the greater part of western Europe. While numy of the statements cited by Bartels are to be classed as legendary, it is of interest to note how persistent and wide in range the belief in the existence of such races has been. The most remarkable stories have been told and have found credence; in these the significance of the caudal appendages has been variously interpreted. On the one hand, a tail has been considered a distinction of the highest degree, even a mark of divine descent, as in the case of the Kanas of Poorbunder; ' on the other hand, it has usually been looked upon as a curse or a stigma of degradation.'

While cai-eful investigation of the many travellers' stories has invariably given negative results regarding the existence of tailed races, so many individual instances of homo caiulatus have been observed, that the popular belief in them has been kept alive without difficulty. With the growing interest shown by anatomists and anthropologists in the subject, the number of cases which have been reported has become considerable, and the fact that the human embryo at a certain period of development is provided with a tail-like appendage has lent color to the discussion of the question. Bartels in 1884 referred to one hundred and sixteen persons who had recorded observations upon tailed men. Of these, over sixty cases had been more or less completely described. In 1892 Schaeffer collected additional cases, adding in all twenty-five. Pyat


' M. Bartels: Die geschwUuzteu Mensclien. Arcliiv f. Aiitliropol., B<1. XV, 1884.

5 These were the rulers of the Jaitwa or Camari, one of the Rajpoot tribes. "They trace their descent from the monkey-god Ilauuman, and confirm it by alleging the elongation of the spine of their princes, who bear the epithet 'Pooncheria, or the long-tailed Ranas of Saurashtra.' " — James Tod: Annals and Antiquities of 'Rajasfhau, or the Central and Western R.ajpoot States of India, vol. i, Loudon 1839.

3 Bartels cites an instance of this in the stories regarding a certain community of tailed men in Turkestan. These were held in the utmost contempt by the other people, and were therefore condemned to constant inbreeding. They were referred to as "Kuju rukly Tatar," which in German is rendered " Stiitkendes ZIhgeziefer mil Schwanzen." The tail was supposed to be a special curse in that it hindered the possessor from sitting properly on his horse.

^Oskar SchaefTer: Beitrag ?.ur Aetiologie der Schwauzbildungen beim Menscheu. Archiv f. Anthropol., Bd. xx, 1833.


nitski ' has also given an elaborate account of the subject, and still more recently Kohlbrugge," in connection with an admirable description of a very interesting case, has made valuable comparisons with previous work. From the United States five cases have, to my knowledge, been reported.'

Undoubtedly we have in these so-called tails a most heterogeneous collection of anomalies. Anything appended to the sacral or coccygeal region is described as a tail. Many do actually bear certain resemblances to the tails of lower animals, and have in fact been compared with a great variety of these. On the other hand, some are vesicular or of irregular shape and accompany the condition of spina bifida, while others are to be classed as teratomata or other tumors. A further very significant fact is that a large proportion of the eases have been complicated by the coexistence of ectopia viscerum, hypospadia, atresia ani, or deformities of the limbs, all of which are known to result from amniotic adhesions. This circumstance has led Schaeffer to the conclusion that human caudal appendages are always due to this cause.'

There are, however, a great many cases in which the anatomical relations of the tail are such as to indicate that it owes its existence to the persistence of at least part of the vestigeal tail found in the human embryo. In some of these it seems that the coccyx extends down into the tail, though there is no good evidence that there is ever an increase over the normal number of coccygeal vertebrae in these instances. Under this latter head would come the majority of the adherent (angewachsene) tails described by Bartels,' and also some


5 1, S. Pyatnitski : On the Question of the Formation of a Tail in Man, and of Human T.ails in General, according to Data from Literature and Personal Researches. Dissertation. St. Petersburg, 1893 (Russian).

« J. H. F. Kolilhrugge: Schwanzbildung und Steissdriise des Menschen nnd das Gesetz der Riichscklagsvererburg. Natuurkundig Tijdschrift voor Nederlandsch-Indic, Deel Ivii, 1S9S.

'Dickinson: A Child with a Tail. Brooklyn Medical .lournal, vol. viii, 1894.

Halsted Myers: j\ Caudal Appendage. Proceedings of the New Tork Pathological Society, (1893) 1894.

Julian Berry: Baby with a Tail. Memphis Medical Journal, vol. xiv, 1894.

A. Ecker: Der Steisshaarwirbel (vertex coccygeus), die Steissbeiuglatze (glabella coceygea) und das Steissbeingriibchen (foveolacoccygea), wahrscbeiuliche Ueberbleibsel embryonaler Formen, in der Steissbeingegend beira ungeboreuen, neugeborenen und erwachsonen Menschen. Archiv f. Anthropol., Bd. xii, 1880. Ecker describes a case reported to him in a letter from Dr. Neumayer, of Cincinnati.

Miller: Medical and Surgical Reporter, 1881. (Not accessible.)

8 Archiv f. Anthropol. Bd. xx, p. 319.

' M. Bartels: Ueber Menschenschwanze. Archiv f. .Anthropol., Bd. xiii, 1881. In this paper Bartels classifies persistent tails, dividing them into two main types, adherent and freely suspended (/roV) ; of the latter


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cases in which the tail projects free from the trunk as, for instance, cases described by Brann,'° Ornstein," and by Dickinson. The majority of the embryonic tails contain, liowever, no prolongation of the vertebral column but are classed as what Virchow"' calls soft tails (weirhe Schivdnze).

Description of Case.

Abont a year ago Dr. Watson exhibited before the Johns Hopkins Hospital Medical Society a baby with a tail, which is an example of the last-named class." The tail was removed later, and through the kindness of Dr. Watson, who gave me the specimen as well as his notes of the case, I am enabled to make a fairly complete report on it, including a description of its histological structure.

The child, which was (lie tliird in the family, was a healthy, well-developed male. In its family history there is nothing which throws any light upon the case. Aside from the tail the baby presented only one other slight deformity, and that was in the four outer toes of the right foot. These toes were shorter than the normal ones of the left foot, their tips were turned up and the nails were small and thick. Tlie phalanges of these toes were short and there were but two in each toe. The great toe of this foot was normally developed.

The tail appendage was attached in the mid-line about one centimeter below the tip of the coccyx. Examination of the saero-coccygeal region showed a well marked foveola coccygca (Eeker) (Figs. 1 and 3), but owing to the extreme fineness of the hairs of this region, which to the unaided eye were quite invisible, it was impossible to distinguish any particular coccygeal bald spot or glabella coccygea (Ecker). Beginning a little to the right and below the foveola is a sharply defined groove, which runs obliquely downward and to the left between the buttocks and passes to the left of the root of the tail.

The appendage itself was of firm consistency, thougli containing no bone. It was covered with normal skin, containing fine hairs, and was apparently well vascularized. Three distinct portions or segments could l)o made out. The basal piece was short and on the dorsal side scarcely marked off from the next following, except when the tail was in a state of contraction (Fig. 2). On the ventral side a transverse furrow separated it from the next portion. The middle segment had a length of 2-5 mm., was curved a little to the right and tapered somewhat towards its distal end, where the much more slender end-segment was attached. These two portions were separated by a constriction more marked on the left side.


a number of subdivisions are made, between wliiob, bovvever, tbc distinction does not seem to me to be sharp.

•0 M. Braun; Ueber rudimentiire Scbwauzbildung bei eiuem erwacbsenen .\Iunschen. Arcliiv. f. Autbropol., Bd. xiii, 1881.

"Ornstein: Scliwauzbildnng beim Menschen. Archiv f. Antlimpol., Bd. xiii, 1881.

'2 R. Virchow : Sebwaiizbilduni^ beim Meusclion. Deutsche uied. Wociienschr., 10. Jahrg., 1884.

'3 W. T. Watson: Exhibition of a Three-nxintlis' Infant with a Caudal Appendage. Proc. J. H. II. Med. Soc. Johns Ilopl^ins Hospital Bulletin, vol. xi, 1900.


The terminal segment curved to the right and ventrally and ended in a rounded blunt extremity. On the whole, the tail gave an impression not unlike that of a pig's tail, a similarity which has been noted' in a number of cases previously reported.

The hairs upon the tail, which were considerable in number, were plainly visible to the unaided eye. They pointed towards the tip, as could readily be confirmed by examination of longitudinal sections (Fig. 4). The convergence of the hairs towards the tip of the tail corresponds with the arrangement of the hairs in the coccygeal whorl {vertex coccygeus of Ecker), found in normal, i. e. tailless individuals, and supposed to be a vestige of the embryonic tail.

Two weeks after the birtli of the child the tail was 4.4 cm. long; at the age of two months it had gi'own to 5 cm.; and at six months, when it was removed, it had attained the length of 7.0 cm., showing altogether a fairly rapid rate of growth.

The most remarkable characteristic of the tail was its movability. When at rest it would lie extended in the midline (Fig. 1), or bent over to one side upon the buttocks. The mother of the child said that she had seen the tail bent through an angle of 180°, its tip pointing towards the head. It must, however, have been brought into this position passively, for, as will be seen later, there was nothing in the arrangement of its muscles which could account for this. When the child was irritated, and cried or coughed, the tail would contract markedly. Between the basal and middle segments but little movement was ]50ssible; the contraction of the muscles merely brought out the constriction between tlie two portions more plainly. Between the middle and distal segments the movement was considerable. The latter could be drawn in sharply, telescoping the middle segment, and at the same time flexion to the left side took place. During this action the middle segment became much shorter and thicker.

When the child was about six months old the tail was removed by Dr. Watson.'* The amputated appendage was put immediately into Zenker's fluid to harden. After it had been washed and kept in strong alcohol for some time it measured 5.3 cm. in length. It was then cut into four pieces with a sharp razor, and the pieces were imbedded in celloidin. Cross sections were cut at three different levels, near the base, proximal to the second joint, and near to the tip, as is indicated in Fig. 4. After a few transverse sections were cut off, the pieces were stuck together and reirabedded in celloidin for the purpose of cutting longitudinal sections of the whole.

From the study of sections it is seen that the skin covering the whole of the tail except a limited area on the ventral sur


" It seemed advisable to remove the tail, not only in order to accede to tbc wishes of the child's parents, who regarded its presence with chagrin, but also on more practical grounds. It loolied as if the tail might become the seat of a troublesome iutertrigo. Besides, its rate of growth was considerable, and it did not seem unlikely that the appendage might have later attained undue proportions, causing, as has been reported in several instances, considerable inconvenience in sitting. (See Lissner: Virchow's Archiv, Bd. 99, 188.5.


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[Nos. 121-122-123.


face is of normal stnicture. The layers of the epidermis are easily distinguishable. The thickness of the skin varies somewhat. Near the base of the tail on the ventral side it is found to be quite 2 mm. thick, while on the dorsal surface of tiie same jjortion it is scarcely 1.5 mm. Further out, i. c. at the middle cut (Fig. 4, a), there is the same difference in thickness between skin of the ventral and dorsal surface (Fig. 5), although the skin is here not quite so thick as at the base. Near the tip the thickness throughout the whole circumference is nearly 1.5 mm. The greater thickness of the skin on the ventral side at the base is due principally to the epidermis, the eoriuni being more nearly uniform throughout. In the thickened area the epidermal ridges extend down deep into the cutis, and the papillse are very long and slender. The various integumentary organs, sweat glands, sebaceous glands and hairs, are numerous and of normal build. In longitudinal sections (Fig. 4) it may be very plainly seen that the hair follicles are obliquely inserted, the hair pointing towards the tip of the appendage. This is without exception the case in the proximal two-thirds of the tail, although the regular arrangement is somewhat disturbed at the crease where the distal and middle segments join, especially on the left side. The corium contains a very abundant supply of elastic fibres which may be readily demonstrated in sections stained by Weigert's method.

Beneath the skin the main bulk of the tail is made up of areolar tissue containing much fat. Blood-vessels, nerves, and striated muscle fibres are imbedded in this mass. There is no trace of anything like the medullary cord or of notoehordal tissue, as Gerlach found in the tail of a fcetus of four months.

The voluntary muscle consists of a few bixndles of fibres which take origin from the subcutaneous areolar tissue near the proximal end of the middle segment. They lie on the left side not far from the mid-line (Figs. 4 and 5), and run distally in parallel bundles diverging somewhat towards their insertion in the skin just beyond the joint between the middle and distal segments. The majority of the fibres are attached on the left side; a few, however, pass to the skin of the right side; and others are attached to the dorsal surface, and perhaps a few ventrally. The action of the muscle is thus clearly explained by its anatomical relations. There are no muscle fibres running between the trimk and the tail.

On the right side near the middle of the tail there are a few muscle fibres (Fig. 5, M'), but these are isolated in small bundles or as single fibres by a dense stroma of connective tissue. Moreover, nearly all of these fibres are in a state of degeneration. The fibrils are less distinct than usual, and the nuclei may be found scattered throughout the substance of the fibres. The muscle is, in fact, in an advanced stage of simple atrophy.

No one of the blood-vessels stands out preeminently in size. The largest artery is on the left side, held in place by strong connective-tissue bundles. This may be seen in sections through the middle (Fig. 5, A), as well as through the base of the tail. There are several smaller vessels in the


vicinity. Two .'=niall arteries are seen in the riglit dorsal quadrant near the centre and one just beneath the curium, to the left of the mid-line. The veins are small and inconspicuous. There is nothing to be seen of a tuft-like branching of the vessels as Virchow " describes in one of his cases, nor is there anything resembling erectile tissue.'" There is, however, an abimdant supply of blood-vessels in the corium.

A number of small nerve trunks (Fig. 5, N) run longitudinally in the areolar tissue of the appendage. The majority of these accompany blood-vessels.

Similar Cases. — While it is not practicable to enumerate here all of the similar cases which have hitherto been reported, there axe some which for one reason or other are of especial interest. The tail of a Moi," ten years of age, which had attained the length of over twenty-five centimeters, is interesting on account of its size. Many of the cases have been described very briefly and only as regards external appearance. There are, however, a number of cases which have cither been dissected or examined microscopically. These include Grove's case described by Virchow," and cases reported by Meyers,'" Vinogradow,"" Eodenacker "' and Scheboldayeff," all of which agree with the present case in general structure but differ from it in the absence of muscle. In two other cases, however, described by Pyatnitzki "" and Gerlach,* respectively, striated muscle fibres were found, and it is to be assumed that such tissue was present in Neumayer's ease, for the tail in this instance could be excited to reflex contraction by stimulation of the sacral region. The complicated arrangement of the muscles found in some instances is associated with the occurrence of bone, as in the case described by Hennig and Eauber,"" and especially in Kohlbrugge's case.'" The tail described by Gerlach in a foetus of 4.6 cm. also contained a continuation of the notochord, which has as yet never been seen in older subjects.

The Tail in the Human Embryo.

The caudal region in human and other mammalian embryos has already been described by Ecker, His, Keibel, Fol, Braun and others. These accounts, while agreeing in the main, bring out considerable difl'erences of opinion as to details. For this reason I give here a further description of the tail


'5 Virchow' s Archiv, Bd. 7il, 1880.

"Bai'tels; Archiv f. Antliropol., Bd. xv, p. 116.

1' Candiil Appeudage in Man. (From tlie French of I^ticnne Rabaud, iu " La Naturaliste.") Scientittc American, vol. 50, 18S9.

18 Virchow's Archiv, Bd. 79, 1880.

'9 Proc. N. T. Pathol. Soc, 1893.

•" K. N. Vinogradow : On Human Tails. Vrach, vol. sv, 1894 (Russian).

■-' G. Rodenacker: Ueber den Saugethierschwanz mit besonderer Beriicksichtigung der caudaleu Anhiinge des Menschen. Inaug.-Diss., Freiburg i. Br,, 1898.

22 W. Scheboldayeff : Tailed Men. Zemsk. Vracb, vol. vi, 1893 (Russian).

■"luang.-Diss., St. Petersburg, 1893.

S L. Gerlach : Ein Fall von Schwanzbildung bei einem menscMicheu Embryo., Morphol. Jahrb., Bd, vi, 1880.

■5 C. Hennig and A. Rauber: Ein neuer Fall von geschwiinztem Menschen. Virchow's Archiv, Bd. 105, 188G.

■■« Natuurkund. Tijdschr. v. Ned. Indiii, Deel. Ivii, 1898.


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region in several human embryos. This I nm enabled to do tlirough the kindness of Dr. Mall, who placed at my disposal his fine collection of human embryos. Two specimens, fourteen and sixteen millimeters long respectively, were found to be especially adapted for this purpose, for it is at this stage that the tail reaches the highest point in its development. The study of these was greatly facilitated on account of their excellent state of preservation, and by the fact that they were cut into perfect series of sagittal sections.

Embryo m. Greatest Length IJi mm. : N eck-Breech 12 mm. — The tail of this embryo is marked oft' vcntrally by a fold of epithelium which extends eranially from the anus, forming a shallow pit or crease between the anal prominence and the tail. This fold extends to the level of the cranial end of the tliirty-third vertebra (Fig. 6), so that from this point on, i. c. distal to the third coccygeal vertebra, the caudal end of the embryo projects free from the trunk.

The vertebral column extends throughout but half the length of the tail, in which, therefore, a vertoliral and nonvertebral portion may be distinguished.

The terminal portion of the tail or caudal filament is bent dorsally and inclined to the left side, and becoming rapidly thinner distally, ends in a slight knob-like enlargement, which is scarcely shown in the figure. The most conspicuous structure in the caudal filament is the medullary cord, which runs to the tip and there ends in a vesicular enlargement. Tlie notochord and the terminal branches of the aorta and inferior vena cava also extend out into it though not so far as the medullary cord. The filament is supported by a diffuse mesenchymatous network, more concentrated in the ventral side just beneath the integument, which is perhaps an indication of the remains of the post-anal gut found in younger embryos.

Counting from the atlas down, it is clear that there are in all thirty-six vertebrae present, of which the distal seven belong to the coccygeal or caudal region. In the trunk, down tlirough the sacral region, the vertebral bodies are composed of embryonic cartilage, which does not stain intensely. The intervertebral discs, owing to the greater concentration of the cells composing them, stand oiit in sections as deeply staining bands. Between the vertebral bodies and the discs there is a zone of cells, which stains more intensely than the cartilage and less so than the discs. In the well advanced vertebrffi of the lumbar region the intermediate zone is thin and clearly forms a part of the perichondrium of the vertebral cartilages. Beginning with the first coccygeal vertebra this intermediate or periehondrial layer forms a thick pad, especially on the distal surface of the disc. The vertebral body is licre proportionately thin, showing itself merely as a lighter streak between the more deeply staining perichondrium of each end. In fact the bodies of the distal coccygeal vertebra; can hardly be spoken of as cartilaginous. In thickness (craniocaudal) the vertebral bodies diminish steadily throughout the sacral and coccygeal regions, but there is very little diminution in the dorsoventraLdiameter xmtil the thirty-fourth vertebra is reached. The last three diminish rapidly towards the


tip. In the last two the discs are fully as thick as the vertebral bodies themselves. The distal surface of the vertebra is capped by a well marked disc. There is on each side of the intervertebral discs in the coccygeal region a small mass of deeply staining tissue, which projects ventrally and laterally. They are visible only in sections which pass to the side of the mid-line. They represent undoubtedly rudimentary hypapophyses or hajmal arches found in the caudal vertcbrse of lower forms.

The spinal ganglia, not counting the ganglion of the bypoglossus, are thirty-three in number. In connection with the ' last a distinct ventral ramus arises and passes ventrally to the side of the vertebrre, bending distally; ventral to the vertebra; it joins a trunk from the next higher nerve. Its mode of ending is uncertain.

The number of muscle plates could not be made out clearly.

In the interval between the thirty-first and thirty-second vertebrffi the medullary cord (med.) becomes siaddenly attenuated into a filum terminale. There are apparently few or no neuroblasts beyond this point; the walls of the tube are made up of columnar epithelial cells. In the distal portion of the vertebral region and at the base of the caudal filament the cord takes a somewhat sinuous course. The central canal extends to the tip of the tail, where it ends in the slight enlargment mentioned above, the terminal ventricle.

The notochord {cli.) forms the axis of the vertebral bodies and discs, and in the proximal portion of the coccygeal region, as in the trunk, is almost straight. In the region of the last two or three vertebra' it is more tortuous. It leaves the vertebral column near the dorsal surface of the last vertebral body and passes thence dorsally to the ventral side of the medullary cord, accompanying this nearly to the tip. In contrast to the vertebral portion, the terminal portion is scarcely differentiated and not well defined in the surrounding mesenchyme.

The continuation of the aorta {ao.), i. e. the a. sacralis media, at first ventral to the vcrtebraj, passes out into the caudal filament as an a. caudalis. From this are given off the segmental arteries, one for each vci-tebra down to and including the last or thirty-sixth. (The last two are not shown in the figure.) These pass up on each side of the vertebral bodies, but it is doubtful if the more distal ones arc as yet fully open. In the same way the vena cava continues into the tail, as the v. sacralis media and the v. caudalis, which lies ventral and to the right of the artery. At their termination in the caudal filament the artery and the vein meet. The vein is of largo calibre to the region of tlie thirty-second vertelira; here it narrows down very suddenly. There are numerous small blood-vessels throughout the mesenchyme of the tail.

Embryo JfS. Greatest Length 16 mm.; Neck-Breecli Jjength IJi mm. — The relations of the tail to the trunk are about the same as in the younger embryo first described, ?'. e. it is free from tlie thirty-third vertebra on.

The vertebral portion of the tail is longer, but the caudal


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[Nos. 131-122-123.


filament is shorter and more shrunken. It bends sharply on itself to the dorsal side, almost through an angle of 180°.

Thirty-seven vertebrae are present, with possible indications of a thirty-eighth; eight of these belong beyond doubt to the coccygeal region. The thirty-foTirth and thirty-fifth are partly fused in the middle. The hypapophyses of each are distinct.

The spinal ganglia number thirty-two. The relations of the notochord, medullary cord and blood-vessels are the same as in the embryo first described. There is a slight irregularity in the notochord in the form of a process wdiich extends ventrally into the substance of the thirty-sixth vertebra.

General Consideeations.

Ecker" and His were the first to give detailed descriptions of the caudal region of the human embryo. Their conclusions regarding its definition and ultimate development may be taken as the starting point in the discussion of the subject. The agi-eemeut reached by Ecker and His may be rendered in part as follows:'" (1) The term "tail" may be applied only to that portion of the embryo which projects free beyond the cloaca. (2) The tail consists of a portion containing vertebrae and a portion without vertebra3 (caudal tUament). The latter contains only notochord and medullary cord. (3) Only the non-vertebral portion atrophies. The vertebral portion remains for some time as the coccygeal prominence (Sleisshbchcr), which, however, gradually disappears in consequence of the increase in the curvature of the sacrum and coccyx, and of the progressive development of the pelvic girdle and its musculature.

Two matters which have a bearing upon the morphological significance of the ])crsisting caudal appendages in man are brought up in the above for consideration. The one concerns the structure of the tail in the human embryo in comparison with the tail in lower forms; the other is the nature and amount of regressive change which takes place in the human tail during development.

Regarding the first, Keibel " discovered an additional fact (if importance in the presence of a post-anal gut in the human embryo. Braun's" observations on' the caudal filament of mammalian and bird embryos are of importance in showing that the caudal filament is of general occurrence and not a ]ieculiarity of the human tail. Again, the occurrence of spinal nerves and ganglia in a number of the coccygeal seg


■- A. Ecker: Archiv f. Aiitbroiiol., Bil. xii, ISSO.

A. Ecker: Besitzt der menscliliche Emliiyo eiuen Scbwanz? Archiv f. Anat. n. Physiol, auat. Abtheil., ISSO.

ss W. His: Anatomie mensclilicher Embryoneii, I, Leipzig, 1880.

W. His: Ueber den Schwanztheil des menscblieben Embryo. Archiv f. Anat. u. Physiol, anat. AbtheiL, 1880.

-9 A. Ecker: Replik und compromissitzc nebst Scblusserkarung von W. His. Archiv f. Anat. u. Physiol, anat. AbtheiL, ISSO.

' Fr. Kevbel : Ueber den Scbwanz des menschliclien Embryo. Archiv f. Anat. u. Physiol, anat. AbthieL, 1891.

31 M. Braun: Eutwicklungsvorgantre am Schwanzende bci eiuigen Siiugethiereu mit Beriicksicbtigung der Verhiiltuisse beim Menschen. Archiv f. Anat. u. Phys. anat. AbtheiL, 1883.


ments, as shown by Fol," Phisalix '^ and Keibel, the continuation of the aorta and vena cava into the caudal filament, together with the presence of segmental arteries and the hypapophyses or rudimentary hjemal arches in all of the coccygeal segments as described in the present paper, show that the caudal region of the human embryo resembles that of other mammalian embryos in all respects except in size and in the number of its segments.

Concerning the regressive development of the tail considerable difference of opinion has been expressed. Rosenberg, who holds that, strictly speaking, the caudal rudiment in man is not the homologue of the tail of other animals, but is the result of a precocious growth of the medullary cord," considers that the appendage disappears in consequence of the increase in volume of that end of the embryonic body and not through absorption. His,'" in supporting Rosenberg, makes the statement that no reduction in the number of segments takes place during the development of the human embryo, but that the regressive changes are confined to the caudal filament; this view is confirmed in the agreement with Ecker. On the other hand, Fol and Phisalix find thirty-eight segments in embryos of 8-10 mm., with indications that several of these disappear through fusion in the course of development. Allowing for the- possibility that these observers have counted in an occipital segment, there would be in embryos of this size at least thirty-seven trunk segments, which would correspond to thirty-six vertebra3. Keibel finds in an embryo of 8 mm. thirty-five trunk segments, together with a mass of unsegmentcd mesoderm, equaling two segments in length. Reckoning this as two instead of one segment, as Keibel does, we have again thirty-seven segment.^, corresponding to thirty-six vertebrae.

The following is an attempt to tabulate the number of segments found in embryos varying in length from 7.5 to 21.5 mm. With the exception of the last column the data are as recorded by the observers themselves. In the last column the number of vertebrse is given which would correspond to the total number of segments after certain changes have been made, such as deduction of occipital segments or addition of unsegmented mesoderm, which seemed justified by the descriptions of the authors.


3- H. Fol: Sur la queue dc rciubryon humain. Comptes Reudus, T. 100, Paris, 188.5.

33 C. Phisalix: Etude d'uu embryon humain de ID milliniotres. Archives de Zool. Exp. et Gen. II"" S., T. vi, ISSS.

■» E. Rosenberg: Ueber die Eutwickeluug der Wirbelsaule und das centrale carpi des Menschen. Morphol. Jahrb., Bd. i, 187G. "... dass die Gestaltung des hinteren Lcibesendes ebeutalls von dem MeduUarohr derart beeinflusst wird, dass letzteres, indem es in seinem Liingenwachsthnm dem der anderen, un der Zusammensetzuug des hinteren Lcibesendes Theilhabenden Bestandtheile vorauseilt, an demselben eiuen Vorspruug erzengt. ..." p. 138.

35 " Es werdeu demnach beim menscblieben Embryo keine iiberzahligen zur Riickbildung bestimmten Segmeute augelegt." Auatomie menschlicher Embryonen, i, p. 93.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XVII.



Fi(i. 1. — I'liotnf;raiiU sliDWiiii;' tail ill exteiuleil cuiuliticiii.


Fiu. 2. — Pliutuyrapli sliowini;' tail in state of ccjiitractioii.



Fig. ;!. — PiKitof^iapli sliowinu; tlie ventral surface of tail.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XVIII.



--M


Fin. 4. — Frontal sections of tail, showing the arranifcnient of the muscle tibres (.V). a. Place from whicli the cross-section represented in Fii;. .5 was taken. x 3.



W/i/i\tl


Fig. .5, — Cross-section through the middle of the tail (Fig. 4, a). M, iinisclc; J/', degenerating muscle ; .1, artery; jV, nerve; i is jilaced on the left and It on the right of the apiicndage. x SI.



Hari-ison del.


Fig. (i. — Caudal region of embryo of 14 nun. (No. 144 of Dr. Mall's collection), combined from several sagittal sections. An.^ auus; .lo., caudal aorta (.1. sncn/?«s Bi«?ia) ; ^'oi. ,/r7., caudal lilament; CA., notochord; ilcd., medullary cord ; S. iii/., ximix iiroi/eiiilulis : I'. :i:i, third coccygeal vertebra; ;i(i, seventh coccygeal vertebra; V. c. i'., caudal portion of fena ctnut ivffflor ( P. ann-aUs mcfjia}. x 1)1.


April-May-June, 1901.


JOHNS HOPKINS HOSPITAL BULLETIN.


101


Observer.


Longtli

of embryo

in mm.


Seg-meuts in mesoderm.


Spinal gjinglia.


Correspoudinj?

numlier of

Vertebnu. Aertel)nr after

allowing for

corrections.


His 7..5

Keibel S.O*

Fol S.0-9.0

Phisalix 10.0

Keibel 11.5*

Fol 13.0

Harrison . . . 14.0

Harrison ... 16

His 16.0

Rosenberg. . 16.5

Fol 19.0

Rosenberg . . 19.6

His 21.5


S.'i 35 _L uiiseEmeiited

meaoderni.

38 —

38 SG

35 _|_ uueeKnienteil 34 meHcideriii.


33

33


34

36

35 36 36 37 34 33 34 35 34


34

36+

36

36

36+

36

36

37

34

33

34

35

34


Neck-breech measurement. t Counting the terminal mesoderm as criui\'aleiit to two segments.

From this it may be seen that the number of vertebrae or their equivalent is fairly if not quite constant in embryos between eight and sixteen millimeters in length. We have, then, seven vertebrae in the embryonic tail at its highest period of development. The stages studied by His and by Eosenberg were either too young or too far advanced to show the maximum number of vertebrae. That the reduction takes place by fusion, as is maintained by Fol, is confirmed by the study of the embryos described above. In the older embryo (16 mm.), in which an exceptionally large number of segments was present, partial fusion between several of the adjacent vertebrse had taken place. In still older embryos, as seen in the table, the number of segments is inconstant; most probably this is due to the varying extent to which fusion has taken place, though it is possible that it may be due in part to a difference in the original number. As Steinbach ■" shows, the usual number of segments is thirty-four, i. e. five coccygeal, although the number may be less or, in I'are instances, even increased by one.

The spinal ganglia of the caudal region, as Keibel has shown, also suffer reduction. There are never quite so many ganglia developed as vertebrse, and the last ones are always more or less rudimentary; but there are always more formed than persist in the adult. For instance, in an embryo of 10 mm. Phisalix described thirty-six ganglia; in an embryo of 11.5 mm. Keibel found thirty-four; in the embryo of 14 mm. described above there were thirty-three, and in the embryo of 16 mm. thirty-two, while in the adult there are but thirtyone. The segmental arteries of the distal caudal segments also become obliterated as development proceeds.

We conclude, then, with Keibel that, while as far as outward form is concerned the embryonic tail disappears largely as a result of the growth of the extremities and the gluteal region, a certain amount of regressive change takes place in the caudal appendage itself. This is manifest not only in the


3« E. Steinbach : Die zabl der CiUidalwirbel beim Mensolieu. mss., Berlin, 1S89.


luaut;


absorption of the caudal filament, as supposed by Ecker and His, but also in the reduction of all essential structures of the vertebral portion of the tail, i. e. the vertebrae, muscle segments, spinal ganglia and blood-vessels. It is interesting to note that in this tendency to reduction the resemblance between human and other mammalian tails also holds. The caudal filament, as Braun has shown, is present in other embryos and atrophies as development proceeds. The tendency to fusion of the distal vertebra? has been observed in the embryos of various long-tailed animals. And in shorttailed varieties, as Bonnet has shown, this tendency is merely accentuated."

The view that a great many of the anomalous caudal appendages found in man are, as stated in the beginning, due to the persistence of the embryonic tail, is warranted by the facts gathered both from the study of the former as well as of the latter. Many of the differences in form are explained by the hypothesis of Bartels that tlie embryonic tail may be arrested in any stage of its development. The soft or boneless tails are clearly not due to the multiplication of vertebra; or even to the persistence of all which are developed in the emluyn, but, as His ™ first suggested, are to be regarded as persisting caudal filaments. The usual position of these appendages as well as their structure support this conclusion. The fact that they are not always attached exactly over the tip of the coccyx cannot be regarded as conflicting with this view, for, as has long been recognized, the curvature in the vertebral column, especially m the sacral and coccygeal regions, changes markedly during" development, and the caudal filament not being firmly united to the tip of the coccyx might easily be shifted slightly in relation to the latter.

In the action of amniotic adhesions Schaeffer^" has suggested a cause which may undoubtedly bring about the persistence of the caudal filament, for it is a fact that in many, perhaps in a majority of the cases there are other evidences of such adhesions having been present, and, as Schaeffer points out, the caudal region, like other projecting portions of the embryo, is especially liable to stick to the amnion. The adhesions are to be regarded, however, merely ns a factor which may induce the persistence of an otherwise transitory structure and it does not follow that such persistence is always the result of adhesions. On the contrary, we find in certain animals that the caudal filament normally persists. According to Braun, this is probably the origin of the tail-stump, composed of areolar tissue, found in Inuus pithecus, and similar apendages are also found sometimes in the Ciiimpansee, as Eosenberg has described.


" R. Bonnet: Uio Rtiunnudscliw;in/.ii;en Hunde ini llinblich aiif die Vererbung erworbener EiKeuseliatteii. Zeigler's Beitriine z. path. .\nat. u. alli;. Pathol., Bd. iv, 18S9.

■'" Anatomie meuschlicher Embryonen, i, p. 95.

™ Archlv f. Anthroiiol., Bd. xx, 1S93, p. 319.


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[Nos. 121-133-133.


DEVELOPMENT OF THE PIG'S INTESTINE

By John Beuce MacCallum, M. T>., Assistant in Anatomy, Johns Hopkins University.


By the work of Henke' and of AVeinberg' it was first shown that the various parts of the human intestine hold a definite relative position in the body. But it was not until 1897, when the researches of Mall' were published, that this subject was put on a satisfactory basis. Professor Mall described in detail the development of the human intestine, the protrusion of loops into the cosloni of the umbilical cord and their return to the general body-cavity. He traced the various loops through different stages in their development and showed that in the human adult these loops are massed together into definite groups, which maintain a constant position in the abdominal cavity.

Merkel,' in his handbook, has considered all the literature on the subject and has given a description of his own work, the results of which are in accord with those of Mall.

Dexter " has lately described the development of the intestine of the cat. He finds no definite arrangement of the intestinal loops to be present in this animal.

The following notes were made in the study of a considerable number of pig's embryos:

Methods and Material.

In this study there was used a series of pig's embryos varying in length from IS mm. to 13 cm. An attempt was made to obtain embryos with each stage, showing only the least possible advance on the one preceding it. In some stages several embryos from the same uterus were examined in order to determine the constancy of the loops of intestine in individuals of the same age. Types chosen from the various large groups of lower animals were also studied.

The only method used was one of direct dissection. The embryos were hardened in formalin or alcohol, which rendered the intestines firm and not easily displaced. The abdominal cavity was opened and the liver carefully lifted away and dissected out under water. The Wolfiian body and kidney were similarly removed. The umbilical cord was then laid open to expose that part of the coelom which it contained. In this way the intestines could be well isolated without disturbing them in the least. Starting, then, with the stomach the various loops were followed and modeled with copper wire. Tliis could be bent so as to accurately represent the direction of each loop, and the general position of the loops of wire could be constantly compared with that of the intestinal loops, so that very little error could arise. On reaching the anus


'Henke; Arch. f. Anat. uud Pliys. Anat. Abtb., IS'.M, S."89. 5 Weinberg; Internat. Monatsch. f. Anat. und Pliys., xiii Bd., 1896. 2 Mall, F. P. ; Arch. f. Anat. und Entwickeluug. Anat. Abth. Supplementbaud, S. 403, 1807; and Anatom. Anz. Bd. 10, S. 4!)3, 1899. ■•Merkel; Handbuch der Topographischen Anatomic, ii Bd., 1899. 5 Dexter, F. ; Arch. f. Anat, und Phys., Anat. Abth., 1899.


the whole intestine was gone over again starting with the rectum and ending in the stomach. In this way any error could be well controlled. The whole model was then compared again with the emljryo to see that the surface coils corresponded. To aid in drawing and studying these models the various groups of coils were painted in different colors. The same method was employed in the study of the lower animals. In the simpler types, however, the wire models were unnecessary. In the earliest embryos also the arrangement could be made out perfectly well without modeling.

Description of Dissections.

Until the embryonic pig has reached a length of about 10 mm. there is in every case some part of the intestine in the umbilical cord. The portion nearest the stomach develops entirely outside the cord; while what corresponds with the lower end of the ileum, together with the coecum and a short stretch of the large intestine, remain in the cord until the stage mentioned above. The part in the neighborhood of the coecum is the last to leave the cord. All the loops which develop within the cord belong to the part of the intestine corresponding in position with the lower end of the ileum. This develops more slowly than the intra-abdominal portion of the gut.

In the following descriptions the terms " right " and " left " refer to the pig's body and not to the figures tlicmselves. "Anterior" and "posterior" refer to the head and tail ends respectively; while the terms "dorsal" and "ventral" are used in their ordinary sense. The figures are all drawn from the right side of the embryo's body unless otherwise indicated.

Figure 1 represents an early stage in the development of the pig's embryo, in which tlie intestine consists of a single loop extending out into the umbilical cord. The embryo itself is 13 mm. long and the loop in the cord is slightly less than 3 mm. in length. This loop is somewhat curved with the concave surface towards the head. As represented in Fig. 1 the intestine is sharply bent on itself in the cord, and on its return to the main body-cavity it turns at an acute angle to form the rectum. I can discover no trace of a ccecum at this stage other tlian a slight enlargement of the tube just after it bends in the cord. The arm of the loop which extends from the stomach into the cord is destined to give rise to the small intestine; while the arm returning from the cord to tlie rectum is, roughly speaking, the forerunner of the large intestine. Several embryos of this size were examined, and the condition described above found to be constant.

In Fig. 2 there is shown the dissection of a pig's embryo, 18 mm. in length. The loop of intestine extending into the cord is much like that represented in Fig. 1. A distinct coecum, however, can be made out in the rectal arm of the


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loop, a short distance from where the intestine bends on itself. This coecum is a short blind sac having an appearance very much like that shown in the iigurc. It will be noticed tliat a considerable part of the body-cavity is, in this stage, in tlie umbilical cord. Fully luilf the length of tlie intestine is contained in this extra-abdominal cielom. Just inside the main body-cavity a loop is beginning to 1)e formed in the small intestine. Its bends are marked 1, 'i and .'5. From the stomach it extends dorsally and to the right. Turning sharply it runs ventrally and to the left, and lieforo entering the cord it ))roceeds again posteriorly. On cumparing Figs. 1 and 2, there is seen a greater change in this part of the intestine near the stomach than in the part contained in the cord. The large intestine beginning at tliu cnn-um turns and passes into the rectum as before. Several enibryos of this size showed an identical structure.

Fig. 3 represents a pig 21 mm. long. The portion of the intestine in the cord is still unchanged, while that in the body-cavity jirojier .shows a further development of the same loops seen in Fig. 2. In comparing the numbers on the two figures there is no ditficulty in recognizing the corresponding parts. The ca?eum holds the same relative position as in Fig. 2. After entering the cord at the loo]) 3 in Fig. 3 the intestine l)ends in a curve with the concave side towards the head. It then turns abruptly backward and to the left, and returns to the main body-cavity by almost the same path. This is represented i)lainly in Fig 3, and it will lie noticed in the succeeding stages that this particular arrangement of the intestine as it turns is quite characteristic.

Fig. 4 shows a somewhat more advanced stage in the develojnnent. It is drawn from the dissection of a pig 23 mm. long. The general position of the intestine is very similar to that just described. The loops, however, have increased in number; and instead of one entire loop, as represented in Fig. 3, there are three, indicated by the letters a. h and c in Fig. 4, B. In Fig. 3 the stomach narrows into the small intestine, which bends rather aliruptly, and forms one complete loop overlying the large intestine. In Fig. 4 the same thing occurs, but following this tirst loop are two others. As shown in the figures there is a tendency for the loops to grow around the large intestine from the right side. The large intestine is on the left side of the small intestine and somewhat anterior. The part of the small intestine contained in the cord is less changed, and its growth is apparently somewhat slower. There is, however, to be seen the beginning of a new coil marked x in Fig. 4, B. This is an incompletelyformed loop and shows well the way in which the loops develop. It is simply a bending, as though the intestine had grown too long for the space it was obliged to occupy. Before reaching the ccecum the small intestine turns on itself in the characteristic way described in Fig. 3. The large intestine is unchanged.

In Fig. 5 the same loops are seen in the first part of the small intestine, and those marked a, b and c correspond fairly wtII. In the cord, however, there are here too loops instead of the one shown in Fig. 4. These occur in the small


intestine ojipositc the ccecum and have relatively the same position as the bending of the tube marked .v in Fig. 4. They are lettered .v and // in Fig. -5. The remainder of the intestine is the same as in Fig. 4. The length of this pig was 25 mm.

Fig. (i represents the intestine of a pig of approximately the same length a? that shown in Fig. 5. The small intestine in the main body-cavity, however, is slightly more advanced in develo])ment. The various loops can be readily recognized and niiuli more easily so on the wii'c model than on the drawing. A very slight change in the general position of a loop causes a most decided dilference in a flat drawing. The main difference, for example, between Figs. .5 and t), is the dislocation of the loop z towards the stomach. By comjjaring the lettering in the two figures this can be easily understood. The part of the intestine in the cord is practically the same in the two figures.

Thus far the large intestine is a simple lube bending shar])ly near the stomach to form the rectum. 11 will be noticed that the small intestine has grown much more rapidly than the large iiitestiiu'; and also that the part of the small intestine neai' the stomach has increased in length uu:ire rajv idly than the part in the cord. Several jiigs, the same size as these last two described, were examined, ami their intestines fomid to be similar in every way. Endiryos tiiken from the same uterus did not seem to resemble one another in this respect more closely than pigs of the same length from different uteri.

Fig. 7 represents a dissection of a pig's embryo 28 mm. in length, and Fig. 8 is a drawing of the wire model made from this intestine. The stomach, it will be seen, occupies the same position and narrows into the small intestine in the same way as before The small intestine here forms a distinct mass of loops in the nuiin body-cavity, and then extends out into the cord in a manner identical with that shown in earlier endiryos. The loops form a cone-shaped mass with the base of the cone towards the stomach and its apex in the umbilical cord. This is due to the more rapid growth of that part of the small intestine near the stomach. This arrangement will be noticed in all the older embryos as well until after all the coils have returned to the main body-cavity. It is a little unsatisfactory to attempt to follow the individual coils of the intestine, and to trace them from one endjryo to another after their arrangement has reached a complexity as great as that shown in Fig. 8 and the figures following. But if the two models represented in Figs 6 and 8 be compared, there will be seen a certain correspondence which can hardly be overlooked. The identity of the two loops in the cord marked .r and // is recognized at first glance. In this part of the intestine there seems to have been very little if any change. The coils near the stomach, however, are distiiutly more complicated in Fig. 8 than in Fig. 6. The slight bend in Fig. 6 marked e is accentuated into the loop marked r in Fig. 8. The letters a and z mark corresponding parts in the two figures; and the loop b can be readily derived in Fig. 8 from the b in Fig. 6. Following this, however, there are in Fig. 8 three distinct loops, c, d and


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[Nos. 121-132-133.


f, without counting x and y; wliile in Fig. 6 there is only one without considering x and y. At d in Fig. 6 there is the beginning of a new loop, as yet only a slight bending in the tube, and c corresponds with one of the three loops spoken of in Fig. 8. There is then in Fig. 6 only one entirely new loop not indicated in Fig. 6.

The copcum maintains the same position in Fig. 8 as in Fig. 6. The bend in the large intestine, however, where it passes into the rectum, shows quite a distinct alteration. It no longer forms a simi^le acute angle with the rectum, but is bent in two directions as shown in Fig. 8. This is the beginning of the formation of a very distinct group of convolutions which is perfectly constant and will be descrilu'd below.

The general tendency in the formation of new loops in the small intestine is for the tube to become slightly bent on itself and to grow around an axis which is represented by the large intestine. The characteristic shape of the loops is shown iu Fig. 8, d and /. The loops do not meet above (on the surface towards the head of the embryo); for the large intestine is situated between the bends of the loops. in such a way that it could be lifted away from the small intestine by drawing it towards tlie head, but not by drawing it towards the tail of the embryo. The arrangement becomes less regular the nearer it is to the stomach, for the gi-owth in this rc'gion is more rapid and the pressure exerted on the coils greater than in other jiarts.

Fig. 9 represents tlie dissection and Fig. 10 the model of the intestines of a pig 30 mm. long. The general position of the various parts is much like that in Fig. 8. By following the letters on Figs. S and 10 the corresponding loops can be made out. There are yet no groups of coils to be distinguished. Tlie small intestine can be roughly compared with a hollow^ cone whose axis is represented by tlie large intestine. The loops ;r and ?/ have become more fully developed and grow around the large intestine in the characteristic fashion. The loops in the figures arc lettered only on the right side, since they arc in a certain sense duplicated on the left side of the large intestine. A loop, however, is a fold which begins and ends somewhere in the same neighborhood; and it might be possible to take the median line as the starting point, and make loops on either side; but it is much simpler to treat as complete loops only those folds which start on one side and return to that side.

The large intestine in Fig. 10 holds a straight course from the ccecuin until it reaches the stomach. It then makes a complete Ijeiid on itself and enters the rectum as shown in Fig. 10, g.

Fig. 11 is the dissection of a pig 32 mm. long, and Fig. 12 is a drawing of the model made from its intestinal canal. A certain general resemblance in outline is seen between Figs. 10 and 12. The intestine is a cone-shaped mass in each with the apex extending a short distance into the cord and the large intestine forming an axis for the cone. The arrangement of the small intestine in relation to the large intestine is the same as that spoken of before. The loops


are bent around the axis of the large intestine, especially near the apex of the cone, i. e. near the cord. At the stomach end the gut has become so twisted that the individual loops cannot be traced with any satisfaction. Certain landmarks, however, can be recognized. For example, the loops .r, y, f and d correspond fairly well in the two stages, and it is not difficult to conceive of the transformation of the loop c in Fig. 10 to the same loop in Fig. 12. This transformation takes place by a flattening of the loop which will be spoken of later. It gives rise to a figure which is often seen in the intestines of pig's embryos.

Although the loops can no longer be individually followed with ease, there begins at this stage to arise a grouping of the coils. In Fig. 12 four fairly distinct groups can be made out. Starting with the stomach end the intestine forms a mass of loops which are situated mainly on the left side of the body. In no place does a whole coil of this grouji reach the surface of the intestinal cone on the right side. Thi.s will be called group A. After bending in five or six loops, as represented in the more liglitly shaded part of Fig. 13 near the stomach, the gut reaches the right side and forms a group of more or less flattened coils, which form all the surface coils of the right side up to nearly the beginning of the cord. This group is shaded darkly in Fig. 12 and ends after the loop marked d. It includes the coil c described above and will be designated group C. The intestine leaves this region at the termination of loop d, and forms three complete loops of the type described in earlier embryos. These are unshaded in Fig. 13 and include /, x and //. They form the group />. These coils are associated more closely than the rest of the intestine with the cadoni of the c(n'd. At the end of this group the small intestine takes a straight path for a short distance and turns on itself in the way seen in all the embryos so far pictured, and enters the large intestine at the cn?cuiii. The large intestine is straight as before until it reaches the region whei'e it turns to form the rectum. Here it is thrown into irregular twists, as shown in Fig. 13, E. The convolutimis formed in this region will be spoken of as the rectal group or group E, and will be followed through the various embryos. At this stage it is directly anterior (towards the head) and lies partly between the groups A and C.

Fig. 13 represents the model of the intestine of an embryo 40 mm. in length. The general outline of the mass of coils is, as before, cone-shaped. This is accentuated by the increasing complexity of the rectal group, and by the rapidity of growth of the first ])art of the small intestine. The same groups described above can be recognized at this stage. The group .1 has increased consideral)ly in length in Fig. 13 and can be divided into two groups which are marked .1 and B in Fig. 13, 11. These become more distinct in later stages. From B the gut passes over to the right side of the body and forms the group C which is situated entirely on the right side, and makes up* most of the surface coils there. This is shaded in Fig. 13, I. On approaching the cord there are found the three complete loops described in Fig. 12, as making up group D. These are almost identical iu the two stages, auu


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extend into the ccrloniie cavity of tlie cord, which has become gradually more shallow. TIic rectal group is more complex than in the preceding stages and forms a conspicuous mass of coils whose calibre is noticealily smaller than in the rest of the intestine. Its position also has altered. Instead of lying between groups .1 and (', it is to tlie right of C, having rotated on an axis corresponding ap]u-oximately with that of the cord. Figs. 14 and 15 represent the dissection and model resjiectively of the intestine nf an endiryo 4.S nun. in length. At this stage all the coils are within the main liody-eavity. The


large intestine begins on the right side of group D, a short distance from its a])ex. The coecum corresponds fairly well in position with that in Fig. 13. On leaving the eoecum, liowever, the large intestine passes obliquely down on the right surface of group C, and is coiled to form the rectal group, posterior to groups .1 and B. Fig. 14 does not justly rejtresent the regularity of the looj)s nuiking up group C. They form a series lying transversely from right to left, and can be easily separated in a mass from group D on the one hand, and croups A and B on the other.



X



w



M


TV



smr'



Fin. 18. — A series of diagrams to indicate tlie formation of groups of coils in the intestine. These represent the intestines of embryos, 13, 21, 2."), 32, 40, 48 and 8.5 mm. in length respectively. The groups are lettered in correspondence with the preceding ligiires. T/// shows the direction in which the groups have rotated, their course being marked by curved arrows.


groups described above can be readily recognized, but a considerable change in their position has taken place. The surface coils near the stomath are derived from group A instead of group C, as in the stage represented in Fig. 13. Group A is on the right side of the body, and group B on the left, (rroup C has moved in a ventral direction and somewhat to the left, until it lies transversely between group D and groups A and B. Group D enters the main body-cavity and the regularity of its coils is lost. Instead of being complete and regular, as in Fig. 13, the loops are distorted and flattened by their association with the other abdominal viscera. The more or less pointed extremity of this group is still directed towards the cord, as shown in Fig. 14. The


Fig. IG represents the surface coils of the intestine of a pig's embryo 85 mm. long. Fig. 16, / is drawn from the ajiimal's right side; Fig. IG, II from its ventral surface; and Fig. 16, /// from its left side. The various groups of coils are lettered in correspondence with those pictured in Fig. 17, which is drawn from a wire model of this intestine. The surface coils on the right side are formed by groups A and D. On the ventral surface groups B and C are present; while the left side is occupied by parts of B and D and the whole of group E. In this stage the same five main groups, that have been described, can be made out. It will be noticed, however, that their relative position is somewhat different. Group D has rotated posteriorly, dorsally and to the right, so


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[Nos. 121-122-123.


that it takes up a position to (he right of, ami posterior to, group C. It thus moves ]iast group C and earrios the coecuni with it, so that tlie beginning of the large intestine lies dorsally, and posterior to grouj) />. The gr(iu|i E is pushed still farther in the sauie direction until it is finally situated in the left dorsal region of the mass of intestines. This group in the beginning lies on the left anteroventral surface. As it becomes more coni])lex it moves around to the right initil it reaches the left dorsal ]iosition. It therefore rotates througii three-quarters of a circle. The axis of this rotation is a line drawn from the beginning of the duodenum to a point somewhat posterior to the umbilical cord.

l*"ig. 18 consists of a number of diagrams of the different stages, showing this rotation of the groups. The straight dotted line in each diagram represents the junction of the main body-cavity and the coelom of the cord. Diagram VI corresponds with Fig. 15, and VII with Fig. 17. The younger stages can be easily recognized. Diagram VIII shows the direction in which the groups rotate. The letters in all the diagrams correspond with those used in the description of the groups; and in VIII these letters, associated with the curved arrows, indicate the direction in which those groups have moved from their original positions.

An appearance which is characteristic of the older embryos is shown in Fig. 16, /, D and C; and in Fig. 16, II, C. The regular loops, which have been described, become flattened by pressure against the abdominal walls, giving rise to the peculiar coiled appearance represented.

The intestines of several embryos older than those represented in Figs. 16 and 17 were studied. The groups were found to correspond with those already described; and an accoimt of these later embryos would not add any essentials to the above description. It is possible in these to tell with considerable accuracy to what group any one surface looj) belongs.

It will lie noticed that in the older stages, «hich have been described, the large intestine grows more rapidly than it does in earlier embryos. In those represented by the first eight figures there is practically no change in the large intestine. After this, however, there gradually appears a consideralde mass of coils to form the rectal group. The part of the small intestine which is at first present in the cord grows more rapidly after its return to the general body-cavity. For this reason as well as on account of the pressiire exerted by the other viscera, the cone-shaped mass of intestines becomes more or less spherical after it is entirely intra-abdominal. The growth, which in earlier stages was almost solely in the region of group .4, is in the older embryos more uniform throughout the gut. The younger the embryo, the more noticeable is this rapid growth in the region of group /i. This fact was observed by Dr. Mall and indicated in his paper by means of tables of measurements. In connection with this it is of interest to note an observation made by Berry," who found that the villi appear first in the upper part of the


« Berry, J. M. ; Anatomisclier Anzeijier, xvii Bd., S. 242, 1900.


intestine. Whether or not the number of villi increases more rapidly in this region than hnver down, has not been determined.

In reviewing a considerable numlier of embryos in this way and modeling their intestines Ijy a method in which errois can be easily controlled, one cannot help being struck by the remarkable constancy of the appearances met with. At first glance it is more noticeable in the earlier embryos. This fact is due to the greater simplicity of the loo]is and to the smaller chance f(u- distortion of the coils by pressure. It will be noticed that there is practically no variation in the portion of the intestine contained within the cord. In that part of the body-cavity there are no other viscera to interfere by ])ressurc with the growth. If it were possible to isolate an organ during its development, its form would undoubtedly be difTereut from what it is when it develops a contact with many other growing organs. The portion of the intestiiie which develo])S in the ccu'd is to a certain extent isolated. The j'npidly-growing viseeia, such as the liver and urinary organs, can in no way intcrfci'e with lis growth; and it is seen from the above descriptions that it is this part of the intestine in particular, which is entirely constant in its appearance. Here the intestine increases in length by the formation of regular loops which grow up and surround the large intestine, as already stated. At first sight it woidd appear that this manner of growth might be caused by the confinement of the intestine in the cylindrical cavity of the cord; but the same method of formation of loops takes place in the general liodycavity before any loops whatever appear in the intestine of the cord. Since it thus takes jilace in two parts of the intestine under difl'erent conditions, it is fair to assume that this is the natural tendency in the growth of loops in the intestine of the pig.

Dr. Mall, in the publication already referred to, has discussed the entry of the intestinal loojis into the ccclom of the cord, and their return to the general body-cavity. He inclines to the belief that the gut is forced into the cord liy the pressure exerted on it by the other rapidly-growing viscera; and that it returns to the main body-cavity on account of a twisting of the loops already contained in tlie abdomen. The dissections of the pig's embryos, which have been described, throw no new light on this subject. The ca?lom of the cord in early pig's embryos is of considerable size and the intestine is at first only a single loop. Hence it is not hard to imagine its being pushed into this easily available space in the cord. Here it remains until the secondary loops are formed, which make up group D. This group is more or less cone-sha]ied and fits into the cavity of the cord which has a similar form. The passing of this group to tlie main body-cavity does not take place one loop at a time. The group returns ajiparently by a gradual obliteration of the cone-shaped cavity of the cord fi'oni its apex to its base.

It can hardly be said that the coils enter the abdominal cavity from the cord in any regular order. The order of their entry is dependent on their position in the mass of coils which projects into the cord. The apex of this mass is formed by


April-Mat-June, 1901.]


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the lower end of the ileum where it turns on itself to join the large intestine. The apex leaves the cord last, and hence the lower end of the ileum is the last part to enter the ahdominal cavity. In the same way the coecum enters a short distance in front of this part of the ileum, simply because it is so situated in the group of coils.

In connection with the development of the mammalian intestine. I wish to call attention very briefly to the intestines of the various lower vertebrates. In Amphioxus the alimentary canal consists of a simple straight tube with no convolutions whatever (Fig. 19, A). In the shark the intestine is straight, but the stomach is bent on itself so as to form a descending, and an ascending part (Fig. 19, B). In the jierch, as in most Teleosteans, there is one distinct loop in



Fio. 19. — Diagrams reiireseuting the intestines of -■!, Ampliinxus; B, Sliarl< ; C, Percli ; I), Frog; E, Turtle; F, Sparrow.

tlie intestine, as shown in Fig. 19, C. There are two methods in these animals l)y which the digestive surface is increased in extent, namely, by the so-called spiral v.-dve and by the pyloric coeca. The spiral valve consists of a longitudinal fold extending into the cavity of the intestine. It is present in all Klasjnobranchs, Dipnoi and Ganoidei, hut not usually in the Teleostei. The pyloric cceea may be very numerous and form a large mass of processes just below the stomach. The spiral valve and the pyloric cceea are seldom both highly develo])ed in the same animal.

In the Amphibia the intestine is, as a rule, much more conijilex than in the fishes. As shown in Iig. 19, D, the frog's intestine is considerably coiled. In a ninn1)er of frogs anil toads which were dissected, tlie intestines were found to be ai-ranged according to a general type which is I'cpicscntcil


in Fig. 19, D. In some cases, however, the coils assumed a much more complicated mass than that shown in the figure. It is interesting to note here that in some stages of the tadpole's life the intestine is a much more complex organ than in the adult frog. The intestine of Necturus shows a coiling which is usually not so great as in the frog.

In the Eei)tilia the form of the alimentary canal is considerably modified by the shape of the body. In Fig. 19, E, is represented the stomach and intestine of a turtle. This is an arrangement which was found to be very constant. In snakes the coils are not so numerous and are somewhat obliterated by the narrowness of the body. In lizards the intestine is coiled more than in either the turtle or the snake. Thus it is seen that in reptiles, and amphibians there is a much more complex arrangement of the coils of intestines than in fishes.

In birds there is a still greater complexity in the form of the intestine. Birds of the same species show very little variation in the arrangement of the coils. In a number of sparrows, robins and blackbirds the arrangement was found to be according to a type represented in Fig. 19, F. There was very little divergence from this type in any of the specimens examined. In the chicken, however, there is a far greater coiling. In several chickens examined there was found a noticeable constancy in the arrangement of the loops. A long duodenal fold extends from the gizzard backward and to the left side of the body. Turning on itself it passes to the right side of the body, where the small intestine is thrown into a number of coils which resolve themselves into two main groups. From the rectum two long coeca extend forward.

In the study of these few lower vertebrates two main points are to be observed: (1) the constancy in the arrangement of the loops in nearly related animals; and (2) the gradual increase in complexity of the coils as we pass from the lowest vertebrates to those higher up in the scale. It is interesting to note also a certain relation which seems to exist between the ontogeny of the intestinal canal in mammals, and its phylogeny. Beginning with a straight tube in the early mammalian embryo the intestine is thrown into a gradually increasing number of loops. Beginning in the same way with Amphioxus we may jiass from the fishes, which possess but a single loop, to the amphibians, whose intestine is much more complex; and fiom these to the birds and mammals, where the alimentary canal is a very much coiled organ.

Recapitulation.

The intestine of a pig's embryo at an early stage consists of an uncoiled tube which sends a single loop out into the ccelom of the cord. The first half of the loop is on the right side and gives rise to the small intestine. From the other half is formed the large intestine. The gut increases in length by the formation of regular loops which grow around an axis corresponding with that of the cord and the large intestine. 'I'hese loops form first in the part which is to become the small intestine. They also develoj) in that part of the small inlesliiie near the stomach before they a]ipear in


108


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[Nos. 131-122-123.


the cord. Up to a certain stage the further growth in complexity is greatest near the stomach. After tlie small intestine has become considerably coiled, a mass of loops is formed in the large intestine. In embryos between 3.5 mm. and -10 mm. in length the group of coils which has formed in the ccelom of the cord, enters the general body-cavity by a mechanism which is not clearly understood. In embryos of the same size the coils are constant in arrangement and definite in their position. Tliey can be followed through various stages of the early development. In older embryos, when tlie individual coils cannot be recognized with ease, they are found to be arranged in distinct groups which have definite situations in the body-cavity. The loops in a certain region of the body-cavity, tliongh they may vary in form, always belong to the same group. These groups arrive at their final situation by a rotation which takes place posteriorly and to the right around an axis, running from the beginning of the duodenum to a point a short distance posterior to the opening of the cord. It is not at all claimed that the surface coils hold always the same position with regard to one another, or that the coils always have the same relation to one another in the group; but it is to be emphasized that the groups always do hold the same relative position in the body.

In lower vertelirates the intestine increases in complexity as we ascend the scale. The intestinal coils are very similar in nearly related animals; and a certain amount of constancy is noticed in their arrangement.

I regret that I have had no opportunity of confirming Dexter's work on the cat's intestine, in which he finds no constancy in the position of the loops. However, from the researches, already referred to, of Henke, Weinberg, ilall and Merkel, as well as from the present study of pig's embryos and the intestines of lower vertebrates, it seems plain that the intestinal canal is an organ which is situated in the body in a definite position, and that its different parts hold a constant relation to one another.


DESCKII'TKIN OF PLATES .XIX-XX.

Fio. 1 Pig's embryo 13 mm. long, showing a single loop of iiitustiu

extending into the umbilical cord.

Fig. 3. — Pig's embryo IS mm. long, showing a loop of intestine iu the cord with a distinct ccecum. The small intestine shows the begining of coils inside the main body-cavity. The dotted line indicates the original outlines of the body before the removal of the liver.

Fig. 3. — Pig's embryo 31 mm. long, showing a slightly more convoluted small intestine. The numbers 1, 3 and '•> correspond with those on Fig. 3.

Fig. 4. — .1. Dissection of pig's embryo 33 mm. in length. B. Wire model of the intestine of this embryo.

Fig. .'i. — Wire model of intestine of pig's embryo 3.5 mm. long. The lettering corresponds with that iu Fig. 4, B.

Fig. C Wire model of intestine of pig's embryo 3.5 mm. long.

Fig. 7. — Dissection of pig's embryo 38 ram. long.

Fig. S. — Wire model of intestine of the embryo represented in Fig. T.

Fig. 9. — Dissection of a pig's embryo 30 mm. long.

Fig. 10. — Wire model of intestine of embryo represented iu Fig. 9.

Fig. 11. — Dissection of a pig's embryo 33 mm. long. C, superficial group of coils on right side of body. The small letters correspond with those used above.

Fig. 13. — Wire model made from the intestines of the embryo represented in Fig. 11. .4, C, D and E, iudicate the formation of groups of coils. The group C is shaded.

Fig. 13. — Wire model of intestine of an embryo 40 mm. iu length. The groups are lettered as in Fig. 13.

Fig. 14. — Dissection of a pig's embryo 48 mm. long. The letters as before iudicate the groups of coils.

Fig. 15. — Wire model of intestines of embryo represented in Fig. 14. Groups are indicated by shading.

Fig. 16. — Dissection of a pig's embryo 85) mm. long, /shows the intestines from the right side; //from the ventral surf.ace; and/// from the left side. The lettering corresponds with that in the previous figures.

Fig. 17. — Wire model of intcstiue of embryo represented iu Fig. Ifl.

Note: — No attempt has been made to retain the relative size of the embryos iu these figures. The actual measurements are giveu iu each case.


BILATERAL RELATIONS OF THE CEREBRAL CORTEX.

By E. Lindon Mellus, M. D.

(From the Aiititotnirnl Ltfbvratonj, Jn/nm Ifttpkhix I'/tift'rxlty.)


In the study of the central nervous system it becomes more and more apparent that the statement that each cerebral hemisphere controls the opposite half of the body must be still further modified. It has long been recognized that certain movements were more or less bilateral; that is, equally controlled by each hemisphere. This is easily demonstrated by electrical stimulation of the cortex and, to a certain extent, the anatomical relations have been worked out. The bilateral representation of most facial movements would appear at first thought to be quite essential and anatomists held, long l)efore it was demonstrated, that each of the motor nuclei in the pons and medulla was connected with its fellow of the oiiposite side by decussating filires. Bilateral movement


could thus be accounted for by simultaneous stimulation of the nuclei of both sides, but the results of some of the more recent investigations show that projection fibres run directly from the cortex of each hemisphere to the nuclei of both sides. This provides for simultaneous stimulation, while the fibres passing directly from one nucleus to the other may conserve the symmetrical discharge of energy.

The necessity for bilateral control of the limbs is not so evident, but the fibres of the so-called direct or uncrossed pyramidal tract in man and the finding of bilateral degeneration in the cord after unilateral lesion of the brain seemed to make it probable. For some time it was not possible to trace tlie cdurse of this homolateral deoeneration from the


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL-MAY-JUNE, 1901.


PLATE ^IX.



Fig. 11,


MacCallum del.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XX.



Fig. 12.



Fig. 14.


Fig. 1:J.



Fig. 15.



MacCallum del.


Fig. 17.


Fig. 16.


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JOHNS HOPKINS HOSPITAL BULLETIN.


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brain to the cord, and various theories were brought forward to explain it. It was considered probable by some anatomists that the pyramidal tract divided at the decussation, some fibres passing to the lateral column of each side, while a portion remained in the anterior column as the direct tract; but in the absence of confirmation Sherrington's theory of " recrossed " fibres was generally accepted. Sherrington's conclusions were based upon experimental unilateral lesions on the brain of the monkey, in which he claimed that immediately below the decussation the degeneration was all on the opposite side of the cord, while at a still lower level degenerated fibres were fomid in botii lateral columns. He thereupon assumed that all the degeneration crossed over in the decussation to the oj)posite side of the cord, but a portion crossed back at a lower level to the lateral column of the same side. The probable explanation of his mistake is that at the time of his observations the delicate methods in use in recent years were not known. Still the fact that he reported at the same time that fibres from the upper limb area of the cortex passed down the entire length of the cord, while fibres from the leg areas disappeared from the cord in the cervical and upper dorsal regions, would indicate that his preparations were handled or studied somewhat carelessly. It is rather curious that no one seems to have suggested that he had mixed up those cords.

Soon after the publication of Marchi's method of staining degenerated nervous tissue by osmie acid, Muratow undertool' the study, by that method, of degenerations following lesions of the brain in the dog. He published the results of his observations in 1893 ' and clearly showed that in the dog the ]iyramidal tract divided at the decussation and a portion ]iassed directly to the lateral column of the same side. I had been working with the same method tracing degenerations in the central nervous system of the monkey after very minute lesions of the cerebral cortex, and at the time of the appearance of Muratow's publication I had already accomplished the same results on the monkey, but to him undoubtedly belongs the credit of priority. These results have since been confirmed by other investigators, and Dejerine and Thomas " and Eisien Eussell' have proved the existence of the same conditions in man.

At the same time I was able to demonstrate the passage of fibres from the pyramid of one side directly to the motor nuclei of both sides in the pons and medulla.'

The following experiment enlarges still further the scope of bilateral representation and adds another to those paths already demonstrated l)y wliich one hemisphere may control more or less both halves of the body. It by no means stands alone, but is presented as the type of a considerable group which will be considered individually in a later publication.

On September 20, 1898, I operated in ]\Ir. Victor ITors


■ ArchtT fur Anatomic und Entwickelungsgescbkbte. 1893. 5 Dejerine and Thomas. Archives, de pliysiol. norm, et patholog. 18%, No. 3. Review in Neurologisehes Centralblatt, 1897, p. 503. sRisien Russell. Brain. Summer, 1898. ' Proo. Roy. Soc. vol. .58.


ley's laboratory at University College, London, on a small but apparently healthy bonnet monkey (Macacus sinicus). The animal being etherized, the cortex of the left hemisphere was exposed under strict aseptic precautions, the centre for thumb movements determined by electrical stimulation and that portion of the cortex carefully excised. Care was taken not so much to remove every portion of cortical substance as to avoid injury to the underlying white matter. I therefore passed the knife under the cortex with the flat surface of the knife parallel to the convexity of the hemisphere, bringing it out at a right angle to the line of incision. Then lifting the cut edge with a pair of small forceps the excision was easily completed. The slight hemorrhage was controlled with hot saline solution, the wound closed with horsehair sutures and dressed with borated cotton smeared with collodion. This monkey got dian-hoea and died on the tenth day after the operation (September 30) of marasmus. The wound in the scalp had healed well and there was no trace of sepsis. The brain and cord were removed, kept for four days in formalin and then transferred to Miiller. The brain was cut into thin segments in a plane nearly parallel to Lhe occipital sulcus (Aft'enspalte), as shown in Figs. 1 and 3, and stained by the Marehi method. It was my endeavor to make the plane of section correspond as nearly as possible to the course of the projection fibres through the internal capsule.

Description of the Lesion*.

Tlie portion of cortex removed was circular and about one cm. in diameter. About one-third of the area of the lesion was in the ascending parietal convolution and the other twothirds in the ascending frontal. Its posterior extremity was about midway between the lowest portion of the interparietal sulcus and the fissure of Rolando, while its anterior boundary was the superior angle of the sulcus precentralis. The lowest portion of the lesion was very nearly opposite the lower extremity of the interparietal sulcus, and it extended upward to the superior frontal sulcus.'* The lesion in the ascending frontal was much more shallow than in the ascending parietal and the entire cortical substance was removed only at that portion of the ascending parietal convolution nearest the centre of the lesion, close to the fissure of Rolando. It was at this point that uncomplicated flexion of the thumb was obtained on stimulation with a weak faradic current. The portion of cortex removed became thinner from the centre" to the periphery of the lesion. In the hardened brain there' was evidence of slight cerebral hernia, i. e. bulging of the brain into the opening in the skull, which accounts for the irregularity of contour in Fig. 3.

In Figs. 1 and 3 I have eiuleavored to show the distribution of association fibres to the external surface of the two hemispheres, the proximity of the oblique parallel lines to each other corresponding to the amount of degeneration found in the various convolutions. It was impossible to


■>» In Fig. 1 the lesion does not extend upward as far as it should. It is better represented in Fig. 3.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 131-122-123.


represent the comparative amount of degeneration so accurately in the outline drawings of transverse sections of the brain (Figs. 3 to 7 inclusive), because in so small a figure, in order to have the degeneration show at all, it was necessary to exaggerate. Degenerated fibres can be seen crossing in the corpus callosnm in all the segments except " E," the most posterior. The distribution of association fibres to the convolutions of the two hemispheres is very nearly equal and quite sj'mmetrical. It extends also upon the internal (mesial)



Fig. 1.

surface of both hemispheres as far as the calloso-marginal fissure.

In two segments, C and D, the degeneration extends to the superior temporal convolution of licith sides. The route taken by the degenerated fibres to reach the temporal lobe is the same in botli hemispheres and is interesting. In section " B " (Fig. 4) a few degenerated fibres appear among the fibres passing to the superior temporal convolution just external to the thickened lower edge of the claustrum on both



Fig. 2.

sides. In the segment posterior to this (Fig. 5) many degenerated fibres can be seen leaving the internal capsule, breaking through the thin inferior edge of the lenticular nucleus and passing below the claustrum to reach the superior temporal convolution. Some of these fibres probably terminate in the lateral geniculate body. Although no continuous fibres could be traced from the internal capsule into the lateral geniculate body, it lies directly in the path of those running to the lemporal lolie and there is considerable degen


eration in this nucleus in both liemispheres. Still posterior to this (Fig. 6) degenerated fibres are passing between the islets of gray matter representing the prolongations of the putamen, while many others may be seen passing down among the fibres of the external capsule. The degenerated fibres in the superior temporal convolution are apparently continuous with both these tracts, the course of which is the same in both hemispheres.

Taking into consideration the movements represented in



Fig. 3.

that portion of the cortex removed, the distribution of association fibres is of especial interest. While the centre for uncomplicated movement of the thumb occupies but a small portion of the area removed, movements of the thumb as part of some associated movement or march may be obtained not only from every portion of that area but also from points considerably removed therefrom — even as far down the convexity of the brain as the lower extremity of the fissure of Rolando. It is a question of much interest whether this is



Fig. 4.

Ijrought about by means of association fibres or projection fibres passing directly from each of tlie widely separated cortical areas to the system of secondary neurons in the cervical region of the cord. It is quite possible that complicated movements may be brought about in either or both ways. The great increase in cortical association tracts between monkey and man suggests the possibility of inconceivable degrees of association.

Looking upon the motor cortex as representing the centres


April-Mat-Juxe, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


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for associated movements one would naturally expect to find projection fibres passing directly down through the capsule from that part of the cortex, giving rise to the movement. As I understand the significance of excitation experiments upon the cortex, the finding of a <?entre for the imcomplicated movement of the thumb only means that in the movement represented at that spot, the movement of the thumb (flexion or otherwise) is the first or initial movement of the march. If the stimulation is continued or increased the



Fig. 5.

march is continued or completed unless interrupted by a .general convulsion. Thus, if the anaesthesia is at just the right stage the gentlest stimulus only excites the first or initiatory movement of the march. In opposition to such a theory it may be urged that only one centre has been found in any single animal for such uncomplicated or initial movement, while many combinations are possible beginning with such movement. This woiild hardly render an entirely separate centre for each movement necessary, as they might ali be grouped about the common centre.



Fig. li.


In experimental destruction of small cortical areas in tlio monkey I have often traced projection filires into the cervicil region of the cord from portions of the facial area far removed from arm centres. Such fibres probably represent the conduction paths for impulses, giving rise to movi'ments in which the arm is associated with facial movement. Such movements or actions are numerous in the monkey and increase as we go u]) in the scale. For example, in feeding, the monkey stretches out his arm, opens the hand Id lay hold


of the object, which he grasps and carries toward his already opening mouth. In this instance the extension of the arm is the initial movement, followed by extension of the thumb and fingers, then flexion, etc. Such a movement or marcli is 'of course much more complicated than any movement obtained by electrical stimulation of the cortex. But it must be assumed that the normal discharge of energy from the cells concerned in the cortical reflex, as a result of incoming sensations, is a very different affair from our experimental stimulation. Stimulation of the motor cortex with a weak faradic current gives rise to certain movements. Cut away the cortical cells and stimulate the cut ends of the projection fibres immediately beneath and you get the same result. Who can say these results are or are not brought about in the same way? Does the former experiment induce a discharge of energy from the cell or does the current passing through the cell to the axis cylinder act exactly as in the other instance? However this may be we cannot safely assume that stimulation experiments disclose more than a hint of the functional activity of the cortex.

A study of the excitation experiments of Beevor and Horsley° on the bonnet monkey shows that they obtained from



the cortical area corresponding to the lesion in this experiment:

Movements of thumb of the opposite side: flexion, extension and adduction:

Flexion and extension of the fingers, opposite side;

Movements of wrist, elbow and shoulder, opposite side;

( 'losure of opposite eyelids;

Turning of the head to the opposite side;

Retraction and elevation of the corner of the moutli, opiiosite side;

Pouting, pursing and rolling in of the lips, more of the opposite side, but often bilateral;

Ojieuing of both eyes and

Eetraction of the head.

The last two were each observed only once in fifteen ex|)eriments. These movements were obtained from various points within the given area but in no single animal were they all observed, nor was any one of these movements obtained from exactly the same point in all the animals experimented upon. Most were primary, though sometimes secondary or tertiary.


■Beevor ami Ilcirsley, Phil. Trans. Royal Society, B. 1887 ami 1S94.


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Nus. 131-122-123.


No purely piimaiT movcincnt was ol)t:i'r\(.'i1 (iT tlio elliow or tlio fintjcrs.

On stiimilation of the cortex of tlie orang outaiig the same investigators ° observed opening of the eyes and turning the head and eyes to the opposite side represented in the same area, or ratlier in that part of it anterior to tlie fissure of Rolando. This march, it will be seen, is also represented within this area in the Bonnet, though not so clearly brought out as in the latter. It is of especial interest in connection with the considerable degree of degeneration found, in the experiment here described, in the superior temporal convolution, now well established as the auditory centre. The association of this cenlre with that jiortion of the cortical area which controls the opening of the eyes followed by synchronous movement of the head and eyes would seem to be the anatomical basis of a cortical reflex of primary importance to self-preservation in all wild animals. It is also to be noted that the distribution of these fibres is quite bilateral. The fact that in this ease they degenerate toward the auditory centre, instead of from it, may be urged against the supposition that these fibres are a link in this reflex, but the anatomical relations of the two centres are certainly intimate and direct.

The feature of special interest in this group of experiments is the large nundier of degenerate fibres passing from the area of the cortical lesion over the middle line in the corpus callosum and down the internal capsule of the opposite side.' With the exception of those fibres going to tlie superior tem]ioral convolution of the opposite side, tlu\se fil)res, in this ex]ierimont, all pass into the thalamus. In a few animals, in which practically the same area was extirpated, some of the degenerated fibres found in the internal capsule of the opposite side can be followed through the ])ons and medulla into the eei'vical region of the cord where they disapj)ear.

Nerve fibres within the central nervous system usually functionate in the direction of degeneration, but there is nothing in the character of the degeneration to suggest the character of the function. This can only be guessed at by the origin, course and termination of the fibres and what


«Beevor and Horsley, Phil. Trans. Royal Society, B. 1890.

' The writer lias found the same thing — degeneration in the internal capsule of both sides after unilateral lesion in the brain, in the dog. In the dog all the degenenatiou in the internal capsule of the opposite side ends in the thalamus.


we know of tlie function of the areas and structures thus anatomically associated. Some of the projection fibres passing inward from the motor cortex clearly carry motor impulses, but it cannot be assumed that all do. A vast number of projection fibres arising in the motor cortex end in the thalamus; I think I may say in the thalamus of both sides. A careful study of the brains of a large number of animals, mostly monkeys, the subjects of experimental lesions of the cortex, leads me to conclude that this anatomical connection of each thalamus with the cortex of both hemispheres is most evident in those instances in which the area excised was that in wliich movements more or less bilateral are represented. These movements are mostly facial; such as are calleil into play in the expression of the emotions. May not this have some bearing on the fuiution of the thalamus? It has been suggested that the thalamus is the centre for reflex or emotional movements.' In unilateral facial palsy the escape of the emotional paths has long been a puzzle. According to present conceptions the cortex is concerned in all reflexes involving consciousness. Many cortical refle.xes are purely voluntary. The part played by volition in those cortical reflexes termed emotional, such as the play of the features in facial expression, is open to discussion, but it can hardly be doubted that they are as much cortical reflexes as any of the so-called voluntary movements. The interposition of the thalamus in such an arc and the anatomical connection of each hemisphere with both thalami, as here demonstrated, may explain the play of the features as the result of emotion when voluntary movement is impossible. In many extensive lesions of the internal capsule fibres passing into the thalamus, even on the side of the lesion, might easily escape injury, even if bilateral control of the thalami were improbable.

As to the functions, other than motor, of projection fibres from the motor cortex, it is at least possible that some serve the purposes of inhibition, voluntary or otherwise. It seems altogether reasonable that voluntary inhibition of certain visual reflexes might be essential to holding the eyes fixed upon a given object. This is suggested as a possible explanation of the presence of degenerated fibres in the lateral geniculate bodies in this case (Figs. 5 and 6). There is certainly no reason why the reflex might not be inhibited in the geniculate body before it reaches the motor oculi nuclei.


8 Bechterew. Leitungsbalmeu im Gehiru uud Riiolienmark. Zweite A ullage.


A NEW CARBON-DIOXIDE FREEZING MICROTOME.

liv ClI.VRLES EUSSELL BaEDEEN, M. D.,

Assnciale in Anatoiiii/, The Johns Hopl-ins Universili/. Bnlliiiiore.


The carbon-dioxide freezing microtomes in common use in pathological laboratories have several drawbacks. Of these the most serious are those due to the use of a rubber tube to connect the tank with the freezing stage. In addition to the


annoyances due to the rubber tube the microtomes are so constructed as to utilize but a slight fraction of the heat absorption due to the expansion of the liquid earlKm-iliiixido. Ill order to oliviale these drawbacks the microtome described


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


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below was devised. In the designing of the original machine I had tJie assistance of Mr. E. F. Xorthrup. In the construction of the present machine I am indebted to Bausch and Lomb, who manufacture it, for several modifications which have simplified tlie instrument and rendered it more useful. Figure 1 shows the machine as it stands ready for use. It is made to screw directly npon the nozzle of the carbondioxide tank. The valve of the latter is utilized to control tlie escape of the gas into the freezing stage. When the microtome is screwed directly upon the carbon-dioxide tank it is necessary that the tank should lie in a horizontal position, on a table for instance, where it may be held in place by some simple clamp. On the other hand, if it is desired to connect the microtome to a tank placed in some other than the horizontal ]iosition an L-'shaped piece of tubing may be screwed on the nozzle of the tank and the microtome on the other end of the L tube. The tank may then be placed in any position desired.



Fig. 1.

A. Cover of freezing stage.

B. Glass track for carrying kuife.

E. Spiral spring.

F. Tubal base of knife-stage. 1. Wheel.

J. Nut for attachiug axial tube to tank. M. Handle of tank-valve. N. Pointer.

The axis and main support of the machine consists of a solid tube with a narrow himen {K-D, Fig. 2). This axial tube is united by a nut (.7, Fig. 1 and Fig. 2) either to tlie nozzle of the tank or to the L-shaped tube mcntidiu'd above.

The machine is thus very readily attached.

On the top of the axial tube the freezing stage (.1, Fig. 1, A-C, Fig. 2) is screwed. This stage piece consists of two parts, a base and a cover. The base is the part screwed into the upper end of the axial tube (C, Fig. 2). To this base the cover-piece is .screwed (.1. Fig. 2). Between the base of the stage and the axial tube is placed a thin brass plate


(D, Fig. 2) with a very narrow aj)erture at its centre. Through this narrow aperture the carbon-dioxide escapes into the lumen of the stage piece (C, Fig. .2). The difference in pressure on the two sides of the brass plate causes a very rapid expansion of gas between the cover and base of the freezing stage. The passage open for the escape of gas from the lumen of the base {C, Fig. 2) to the external world is in the form of a s])iral passage which finally opens out through the side of the cover, as shown in (Fig. 1, .1). Between tlie cover and base of the freezing stage an asljestus washer is ]i]aced. The exjianding gas therefore can absorb little heat from the base of the stage. Almost all heat absor]ition must take place from the cover. This heat absorption is greatly facilitated by the metallic spiral which projects down from the cover so as to give rise to the spiral passage through which the gas escajies.

Througli the mechanism here descrilicd far the greater part of the heat-absorbing power of the expanding gas is utilized

A B



G l^



A. B. C. D. E. F. <i. H. I. J. K.


Fig. 3.

Cover of freezing stage.

Glass track for carrying-knife.

Aperture in base of freezing stage.

Aperture in thin brass plate.

Spiral spring.

Tubal base of knife stage.

Check for limiting movements of knife-stage.

Groove for G.

Wheel.

Nut for attaching axial tube to tank.

Opening into lumen of axial tube.


to lower the temperature of the surface of the cover of the freezing stage. The temperature of the rest of the machine is but little altered. Good control of the temperature of the freezing stage can be thus maintained. This control is farther rendered possible by the valve of the tank. If this valve is turned on full the temperature of tlie cover nf the freezing stage is quickly reduced to a very low point. Tissue placed


lU


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


on it is quickly frozen. On the other hand, if the gas is not allowed to escajie from the tank with full force the difference in pressure in the two sides of the brass plate is less and heat absorption from the cover is less marked. In this way tissues placed on the cover may be slowly frozen without suljjecting them to severe cold. Thus, too, a constant low temperature may be maintained by opening the tank-valve to the required point.

The mechanism for controlling the thickness of the sections is equally simple. On the lower end of the axial tube a movable wheel {I, Fig. 1 and Fig. 2) is placed. This wheel moves up and down the axial tube on a screw thread cut twenty-five threads to the inch. A complete revolution of the wheel therefore raises or lowers it a millimeter. The margin of the wheel is divided into fifty spaces, each of which therefore represents twenty microns. A pointer (iV. Fig. 1) serves to indicate the number of spaces passed in a partial revolution of the wheel and thus to show the thickness of the sections cut.

The knife-stage {F-B, Fig. 1 and Fig. 2) consists of a tubal


base (F). whii-li surrounds the axial tube and rests on the mova1)le wheel; and of two flanges {B) which extend above the freezing stage on each side for the support of the cutting blade. The base of the knife-stage is moved up the axial tube by screwing the wheel ujiwards. It is forced down the axial tube by the spring (E, Fig. 1 and Fig. 2) whenever the wheel is turned so as to be carried downwards. Tlie flanges of the knife-stage support parallel glass tracks upon which the cutting blade is carried to and fro.

For cutting sections a razor or a plane or almost any good steel blade with a straight edge may be used.

The advantages of the machine are as follows:

1. But little carbon-dioxide is wasted.

2. The temperature of the freezing stage can be controlled.

3. Owing to the nature of its attachment to the tank it can be readily carried about. This should render it of especial value to surgeons.

4. Above all it is simple in design, strong, and unlikely to get out of order.


NOTES ON CERVICAL RIBS.


(Froii) the Aniitninii'id Luhoratorij

Altliough nianv cervical ribs have been described hereto


fore, the following description of three cases is given because of variations presented which, while most of them have already been recorded, are somewhat rare.

(Jase I. Fig. 1. The dissection of this subject was nearly completed before the cervical rib was noticed, so that most of the soft parts had already been removed before it came to my hands.

There was a cervical rib on each side, the left being much better developed tl-an the right. Each rib was made up of head, neck, tubercle and shaft. Each articulated with the seventh cervical vertebra on the body and on the transverse process. There was a simple stellate ligament at the costocentral articulation, and a capsular ligament at the articulation of tlie tubercle with the transverse process.

The left rib extended down to the upper liorder of the first thoracic rib, witli which it articulated, lieing held in position by a capsular ligament. There was a slight articular eminence or facet on the first thoracic rib at the point of articulation, the facet apparently corresponding to the scalene tubercle of a normal first thoracic rib. The left cervical v\h projected a distance of 2.3 cm. beyond the body of the seventh cervical vertebra and then curved sharply downwards. The extreme width of the rib was at this point, where it measured !.(! cm. The shaft of the rib was triangular in cross-section and measured .4 cm. in thickness.

The sevcntli cervical nerve on the left side crossed the middle cif tlu' livoad up]ier half of the rili in a well marked groove.


By Clinton E. Brush, Jr.

of file Jiihiis Iliipktns Unlfersili/.)

At a point 2.G cm. from the distal end of the rib was the superior border of a sharply defined groove, .9 cm. in width. Across this jiassed the lower trunk of the brachial plexus (1), the eighth cervical and first thoracic nerves uniting before crossing the rib. As the truid'; of the brachial plexus was



YlG. 1.

C.^SE I. — 1. Lower cord of brachial plexus. 3. Sui)pleineiitar_v iutereostal uerve. 3. Fibrous cord.

but .4 cm. in diameter, it is probable that the subclavian artery also crossed iu this groove.

In the supplementary interspace there were some well developed muscle fibres, but their condition was such that it was impossible to decide wliether or not tliere had been both an inner and an outer set. ,lust before crossing the upper border of the first tiuu'acic rib, the eightli cervical nerve


Ai'iai.-MAY-JrM-;, lOdl.]


JOHNS PIOPKINS HOSPITAL BULLETIN.


115


<iave off a small branch (2), which divided into several smaller twigs to innervate the supplementary intercostal muscle.

The right cervical rib corresponded very closely in size and shape to the upper half of the left rib. It extended 1.7 cm. beyond the body of the seventh cervical vertolira and was 1.4 cm. wide. The upper border curved sharply downwards and met the lower border 2.6 cm. below tlip tuliercle. so that the rib ended in a point. From this pointed end a round, lihrous cord (3) extended to the first thoracic ril). meetiui;- it al a point corresponding to the place of articulation of tlie left cervical i-ib with the first thoracic rib (ui tlie left side. l'"r(ini bere the fibrous cord was continued along tlie superidr liin-ilcr of the first thoracic rib to the stcrntnn.

On the riglit side also the supplementary inlers|iace C(intained well developed muscle filires, the nerve suiiply lieing similar to that on the left side.

'I'he distribution of the arteries that were still on the subject was normal, except that nn buth sides the verteljial arteries passed up to enter the foramina of the transverse processes of the fifth cervical vertebra.



Fig. 3.

Case II. 1. Groove for subclavian artery and lower cord of brachial

plexus. 3. Groove for VII cervical uervc. 3. Ligament. 4. Capsular liijauient. 5, (I, 7 and 8. Liijaraeuts.

Case II. Negro woman. Age, a1)out GO years. Fig. 2. Vertebral formula— C, 7; T, 12; L, 5; ,S', 5.

This subject possessed two well developed cer\ieal ribs, that on the left side being much better developed tliau that on the right. Each rib consisted of head, neck, tubercle and shaft. Each articulated with the seventh cervical vertebra in two places — the liody and the transverse process. The right rib articulated with the superior border of the first thoracic rib, G.9 cm. from the head of the latter. The left rib was ankylosed with the superior border of the first thoracic ril), the central point of the ankylosis being 5.5 cm. from the head of the thoracic rib.

The general shape of the two ribs was the same, the upper part of the shaft being broad and flat and then rapidly narrowing down to a shaft which was triangular in cross-section.


Each rib presented two grooves. One (1) which was very well defined, was on the anterior surface of the narrnw pail of the shaft for the }ias.sage of the lower trunk of the brachial plexus and the sid'clavian artery. The other groove (2) was very slight and extended outward across the broad upper part of the sliaft for the ]mssage of the seventh cervical nerve.

The dianieier of tlie first thoracic rib on the left side from its lu'ad to the ankylosis with the cervical rib, liu( more especially in llw nock, was much less than tbat of tbe right thoracic rib in tbe same part. Beyond the ankylosis it was nbdnt the same width as the right rib was lievmid its articnla'tion with the cervical rib.

From the ti|> of the right t'ci'vical rib a round lilu'ous coi-il extended to Ihe sternum along the superior bordei' (if Ihe first thoracic rib, being closely adherent to the latter. A similar cord was present on the superior border of the left thoracic rib, being continued from the ankylosis.

The ]n'iiu-ipal measurements of the ribs were as follows:

Right. Lett.

Head, neck and tubercle 3.6 cm 2..S cm.

Straight line from back of tubercle to

end of rib 4.7 " 4. .5 "

Length along' concave border .5.7 " O.ti "

Breadth of upjier part of shaft l.o " I. .5 "

Diameter of lower part of shaft 4 .6 "

Diameter of neck of first thoracic rib 1

cm. from its head 9.5 " .5.5 **

On the right side, the scalenus anticus had a. normal origin, but was inserted on the tip of the cervical rili anil on the sitperior border of the first thoracic rib for 1 cm. anterior to the articulation of the two ribs. The scalenus medius was inserted along the superior border of the cervical rib from the tubercle to the upper border of the groove for the subclavian artery and lower cord of the brachial plexus, 2.3 cm. from the distal end of the rib. At the lower end of the insertion some of the filn'cs were prolonged downwards across the inner surface of the supplementary interspace to be inserted on the upper border of the first thoracic rib for l.l cm. jjosterior to the articulation with the cervical rib. The scalenus posticus was inserted on the outer border of the cervical rib at a point l.t! cm. from the tubercle, in connection with the scalenus medius, and thence by a fibrous band, .3 cm. wide, backward and downward to the superior boi-der of the first thoracic rib for a distance of .5 em. on that rib.

The supplementary interspace on the right side was fillett by two well developed intercostal muscles, an outer and an inner. The external intercostal arose from the outer inferior border of the cervical rib from the head to the extreme end of the rib. The fibres extended downward and forward to be inserted along the superior border of the first thoracic rib. The fibres arising from the end of the cervical rib spread out in a fan-shaped insertion along the anterior face of the first thoracic rib for a distance of 2.5 cm.

The internal intercostal muscle arose from the inner border nC the infi'i-idi- sni-face of the rib, the fibres running downward and backward to be inserted along the inner border of the first thoracic rib for a similar distance. This muscle was


116


JOHNS HOPKINS HOSPITAL lUTLLETIN.


[Nos. 121-132-123.


innervatoil liy (ibrcs from the interfostal ln-aiu-h of tlie first tliorMcic iKTVt'. This branch ran ahiii<>- tlie superior border of tlie second tlun-acic rib and sent its fibres across the first rib io the su|)plcmeutary intercostal muscle.

Tlie eifihtli cervical and first thoracic nerves united at the inner boi'der cd' the cervical rib to form the lower trunk of the brachial plexus, which crossed the rib above the subclavian artery. Just i)efore uniting with the eighth cervical nerve, the first thoracic gave off a slender blanch which descended along the inner border of the rib, behind the suljdavian artery, to the lower end of the rib, where it turned upward to gain the surface, wound around the end of the rib and was distributed to the articular ligament.

The right rib articulated freely with the seventh cervical vertebra and also with the first thoracic rilj. A stellate ligament held the head of the cervical rib to the vertebra. Besides this ligament there was a superior costocentral ligament (3) passing from the superior surface of the neck of the rib mainly to the lower outer border of the body of the sixth vertebra, a small slip being continued upward and outward to the anterior inferior border of the transverse process of the same vertebra. A capsular ligament (4) held the tubercle of the rib to the transverse process of the seventh vertebra.

The disposition of the soft parts of the left side' was very similar to that of the right. The scalenus anticns was inserted by a fan-shaped set of tendinous fibres to the lower half centimeter of the cervical rib, and was continued along the superior border of the first thoracic rib for 1.6 cm. anteriorly. The scalenus medins was inserted along the superior external border of the cervical rib from its head to the upper margin of the groove for the subclavian artery, 2.3 cm. from the central point of the ankylosis. The scalenus posticus was inserted on the superior border of the first rib. The iliocostalis dorsi sent a sliiJ of insertion to the external border of the cervical rib and also one to the tubercle. On the right side the slip to the tubercle alone was jjresent.

The external intercostal muscle in the supplementary interspace was well developed. It arose from the outer border of the inferior surface of the cervical rilj from its head to the ankylosis. The fibres, running downward and forward, were inserted along the superior border and external surface of the first thoracic rib for a somewhat longer distance. The internal intercostals arose from the inner inferior border of the cervical rib, from the ankylosis to the tubercle, and extended downward and slightly backward to l)e inserted for a similar distance along the superior inner border of the first thoracic rib. The innervation of the supplementary intercostals was similar to that on the right side — l.iy branches from the first intercostal nerve.

The left cervical rib articulated freely with the seventh cervical vertebra, but was firmly ankylosed with the superior border of the first thoracic rib, the ankylosis covering a distance of 2.2 cm. The tubercle articulated with the transverse process of the seventh vertebra, the joint being effected by a capsular ligament, no distinct division into smaller indi


vidual l)ands being noticeable. From the ui'ck of the rib. .just within the tubercle, a filirous band (5) .•"> em. in width extended upwai'd, backward and slightly inward to the lower ])osterior border of the transverse process of the sixth vertebra, and to the anterior face of the transverse process of the seventh. A small ligament (fi) connected the superior external margin of the liead with the lower, outer border of the body of the sixth vertebra. Just internally to this, and arising friuu the middle of the superior surface of the lu'ad. a band .3 cm. wide (7) extended u})ward ami inward to the lower outer border of the sixth vertebra, the insertion being under and inside of that of the smaller slip. Posteriorly to these, another ligament, .G cm. wide, connected the superior posterior surface of the head with the lower border of the body of the sixth vertebra. A shoi't, tough, fibrous cord (8) extended from the inferior surface of the head of the cervical rib to the superior surface of the head of the first thoracic rib. From the upper half of the head of the cervical ril) a stellate ligament extended to the body of the seventh vertelira.

The arterial distribution on both sides was normal except for the origin of the left common carotid from the innominate artery immediately after the latter left the aorta.

There was a distinct skoliosis to the left side in the upper thoracic region.

Case III. This was simply a cleaned specimen of a rib from the anatomical museum. Nothing was known about the subject from which it came.

The specimen was that of a left first thoracic rib, having a cervical rib ankylosed with it. The ankylosis was so complete and the free part of the cervical rib so shoi't that it would be better to class this as a bicipital first thoracic rib. Its morphology is very similar to that of the bicipital ribs described by Turner.' The rib presented two heads, two necks, two tubercles; and, for a distance of l.G cm. beyond the tubercle of the upper division, there were two shafts. That point marked the posterior limit of the ankylosis, which extended forward a distance of 4 em. On account of the ankylosis, the rib was very broad at this part, being 2.(i cm., while the true shaft of the first thoracic rib beyond the fusion was hut 1.7 cm. The two necks were separated by n space .6 cm. wide.

The principal uieasui'cments of the rib were as foUow's:

From tip of lie.ad to outer border o£ tubercle, (upiier divisiou). .'3.4 em.

II '• " ■' " " (lower division). S.li "

Widtli of necl<, (upper division) S "

" " (lower division) ... .7 "

Straight line from head of lower division to dist;il end of rib. S..") " Length along convex margin from head of lower division to

distal end of rib 1'.>.3 >■

The U]ipcr border of the rib ])resented two grooves, one crossing just anterior to the central point of the ankylosis and the other .7 cm. anterior to this. In the recent state the subclavian artery and lower cord of the brachial plexus undoubtedly crossed by the former, while the latter was prob


' Journ. Anat. and Physiol., 1883, vol. xvii, pt. ill.


Ai'Ril-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


117


ably for the passage of the subclavian vein. Between these two grooves there was a very prominent pointed process, projecting 1 cm. beyond the upper border of the rib. The anterior margin of its base was also the anterior limit of the ankylosis. From its general direction and from the fact tliat there was a visible groove along the line of ankylosis, it seems probable that this represented the tip of an originally free cervical rib. In the recent state there was probably a tibrous (Mird extending from the tip of the process to the slernnni.

SOMMAKT.

Of tliese three cases, the first two present some uiicoiiinion \ariations. In the first case the innervation of the supploiiiciitary intercostals by a direct intercostal branch from the eiglith cervical nerve has been described only once." The second ease shows a peculiar insertion of the serratns posticus on the first thoracic rib. This has also been described by Grubcr,' but it is not mentioned as a variation in the standard


Mem. de 1' Acad, des Sc. de St. Petersbourg, 1869.


text-books, nor is it spoken of by Le Double.^ This case also presents the following variations, wliich, so far as I can find, liave not been reported heretofore: a minute brancli from the right first tlioracic nerve to the articidar ligament l>etween tlie cervical and first tlioracic ribs; a ligament connecting tlic licad of tlic left cervical rib witli the head of the left first thoracic rib, and a ligament from the neck of the cervical ril) to the lower border of the transverse process of the si.xth vertebra (Fig. 3, 5). I^or a full list of references to the subject of cervical I'ibs the recent article by I'hillips' may bo consulted.

In conclusion 1 wish to express my thanks to Dr. K. (). Harrison, at whose suggestion the work was originally undertaken, for his advice and assistance in my work.


■' Traite des variations desSystcme masculaire de 1' liommo. Paris ISltT. Tome I.

Jouru. Aiiat. and Physiol., l',)00, vol. xx.\iv, D. s. xiv, pt. iv.


ON THE PRESERVATION OF ANATOMICAL MATERIAL IN AMERICA BY MEANS

OF COLD STORAGE.


By Abram T. K Assialaiit Profc.tsor of Anaiumij,

The pi'cservaliun of the dead body and its pre}iaration for dissection ha\e always been problems to the teacher of anatomy. The methods of preservation are different according 1(1 the object in view; certain methods being employed when it is only desired to keep the body for the ordinary dissection; others, when special parts, systems, or regions are to be worked out; and still different methods when it is desired to store material for months or years. One great step was made in the process of preservation of anatomical material for dissection when Frederic Euysch, the Dutch anatomist, introduced the method of embalming by means of injection. This was further developed by William Harvey and has been brouglit to great perfection at the present day both by the anatomists and the professional embalmers. The various methods employed in most of the principal European schools have been carefully described by Dr. Iljalniar Gronoos in the Auatoniischer Anzeigcr for September 28, 1898; and a report upon the various methods employed in America was jirepared by a committee of the Association of American Anatomists and ]iublished in Science January 17, 189G.

The ra]iid development of medical education has called for the introduction of more lalioratory work in the first two years of the course, and this, together with the increased tendency to concentrate medical teaching in the larger colleges, has made it necessary to collect dissecting material during the whole year and to develop methods which shall preserve it in good condition until wanted.

The method of pickling, that is, placing the body after it


ERR, B. S., M. D..

Cornell Uiiircrsili/. Il/nira, N. Y.

is embalmed and injected into a large vat of brine or some other fluid, is being quite generally abandoned. It is replaced in some institutions by enclosing the bodies in tightly sealed boxes, in which there is an inch or more of alcohol on the bottom and the body is surrounded by alcohol vapor. In other places the use of cold is employed to keep the bodies until they are needed.

Cold is produced according to the well known law of physics, that heat is required to change a solid into a liquid, or liquid into a gas. This heat is abstracted from surrounding substances. For the preservation of cadavers the cold was produced until the past few years by the melting of ice. either alone or combined with salt. But within recent years refrigerating machinery has been so well perfected, and the cost of these machines has been so much reduced, that to-day there are ten medical colleges in the United States whicli have installed refrigerating plants. The principle on whicli these machines work is very simple. It is well known that it requires much more heat to vaporize a liquid than to li([ucfy a solid; thus to liquefy 1 gram of ice_ it requires 80 heat units, but to vaporize 1 gram of water it takes 537 heat units. Therefore in the freezing machine a volatile li(|iiid such as ammonia or ether is used. The machines on the market to-day are mostly ammonia machines.

The first ice machine to be used to preserve dissecting material was installed by the College of Physicians and Surgeons, Columbia University, New York, and when it had been in operation long enough to show the practicability and advan


118


JOHNS HOPKINS HOSPITAL BULLETIN.


LN,


iai-122-123.


tages of this method plants were installed 1\y the Johns Hopkins and by the University of Pennsylvania and later by Syraense University, Long Island College Hospital, the University of Buffalo, Jefferson Medical College, the University and Bellevne Hospital Medical College, Cornell University Medical College, New York City, and a iilaiit is to be liuill this year by the Cornell I'liiversity Medical College at Ithaca, N."y.

Last A])ri], at the siigge.Midn (d' Dr. .Mnll. I |iiesi'nted before the Association of American Anatomists at Washington a very brief account of the plant installed at the University of Buffalo. At this time 1 wrote to the pnifessors of anatomy in all the institutions where 1 knew that they had cold storage plants and askeil for certain statistics in order to compare their residts with those obtained by me at the University of Buffalo. From some of these which I am permitted to use, and from the articles of Dr. iMall ' on the cold storage plant at the Johns Hopkins, and of Hr. Ibilnies' on that at the University of Penn.«ylvauia, I wish to call attention to those things which it is desirable to incorporate in a plant and those which slunild be avoided. I desire at this I'.dint to express my thanks to the professors in the institutions named above for furnishing me with data regarding the ice machines and vaults employed by them.

There are two systems in use at the present day. In the ammonia-absorption system a solution of ammonia in water is heated, the ammonia gas passes off into a condenser where the constant distillation raises the pressure and the heat being absorbed by a stream of cold water, the ammonia becomes liquid. The liquid ammonia is conducted to the refrigerating coils, where it again becomes a gas and by thus vaporizing produces cold. The gas then passes to another chamber, where it is absorbed by a weak solution of ammonia in water, and the strong solution resulting is returned to be heated again. This type of apparatus is said to have some advantages over the other system, as its relative cheapness and lack of complicated machinery, but it is also deficient in several respects. The Long Island C(dlege Hospital is, I believe, the only medical school which has an apparatus of this kind.

The ammonia compression machine is the one most generally used to-day. This consists essentially of three parts, as shown in the figure of the plan at the Johns Hopkins University. The evaporating coils arc the inpes in which the liquid ammonia changes to a gas and absorbs heat from its surroundings. The compressor is a combined suction and compression pump which draws the ammonia vapor from the evaporating coils and forces it under pressure into the cooling coils. These are long lines of pipes immersed in running water, and under the combined action of the ])rcssure from the pumj) and cold from the water the ammonia gas is here reconverted into a liquid and passes again into the evaporat


ing coils. The lldw is of course regulated l)y valves and pres


' Franklin P. Mall, The .Anatomical course and Laboratory of the .Johns Hopkins University, Bulletin of the .Johns Hopkins Hospital, Baltimore, May and June, 18!)6, vol. vii, Nos. 62-63.

• E. W. Holmes, Refrigeration as a means ol preservation of Bodies for use iu the Dissecting room, Internal. M. Mag. Phil., ISIIT, vi, 747-741).



NV.^^ \\\\\\\ \vCv


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sure gauges. The compression machines are utilized in two


Apkil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


119


ways. In the one the evaporating or expansion pipes are distributed directly in the room which it is wished to cool; in the other these coils arc distributed through calcium chloride brine and the cold brine is pumped througli the


Jfachines are rated in two ways, according to their icemaking capacity, and their refrigerating capacity. The latter is usually taken as twice the former. The unit of ice-making capacity is one Ion of ice at 32 degrees F. frozen from water



Insulation


^Tine tartK


/


Fig. 2. — Outline of the cold storasje vault at the Uuiversity of Penusylvania. The brick wall ou the outside is striated.



K^


vy


Fiu. '■'). Section of the cold storas;e vault at the I'liiversity of Bullalci

rooms which it is desired to refrigerate. The first of these is known as the direct-e.xpansion method, the other as the indirect. Johns Hopkins and Syracuse have the indirect and Pennsylvania and Buffalo the direct.



Fig. 4. — Section of the wall and insulation of the vault at the University of Pennsylvania. BP, one layer of building paper; A, half-inch'air space.


at 32 degrees F., and is equivalent to 281,000 heat units per 24 hours.

It is quite imjiortant to get a machine large enough for the work required of it. The size will be influenced greatly


120


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 131-133-133.


by location, insulation, and so fortli. Very satisfactory work is being done at Syracuse by a macbinc of 3 tons refrigerating capacity for a vanlt of about 3(100 culjic feet. At Buffalo a 3-ton machine for about 1.500 cubic feet, at Johns Hopkins a 4-ton machine for 3300 cubic feet, at Pennsylvania a G-ton is used for about 4300 cubic feet. The cost of such a plant varies from $3000 to $3000.

AVhetlicr the machine works on the plan of direct radiation or indirectly by means of brine, it is a very great advantage to have within the vault a considerable body of brine which is cooled when the machine is running and which holds the cold, giving it out gradually and keeping the temperature of the vault from rising rapidly when the machine is not running. These brine tanks are cooled by coils of ammonia expansion ])ii)es running through them. In the Johns Hopkins plant, where this device was first introduced, there is


around the sides of the upper jiart of the vaidt or along the ceiling, or botli. This also heljis the circulation and })revents a warmer stratum of air from collecting above and a cold stratum Ijelow. The circidation of the air in the vault is only maintained during the running of the machine, as the temjierature of the e.xpansion pipes soon becomes the same as that of tlie surrounding air when the machine is shut down.

The size of the machine rc(|uired is of course influenced greatly by the size of the vault and its insulation, and the number of hours per day which the machine is in operation. In all of the above-named plants there is more than enough cold produced. The excess of cold can be used to cool some of the dissecting rooms in summer, as is done at Columbia and at Cornell, N. Y.

The construction of the vault is one of the most important



Fig. .5. — Section of the iusulatlou of the ceiling of tlie vault at the University of Buffalo, li, BoarJs space one-inch wide; /', buihiiug paper.


-inch thick ; .1, air


sw



Fio. 6. — Section of the insulation of the side walls of the vault at the University of Buffalo. ,S'ir, stone wall; P, building p.iper.


one large tank situated in one corner of the vault. Since they use the indirect method tiiis tank alone is cooled by ammonia expansion coils and the cold brine is taken from the tank and pumped througji the pipes in the vaidt. At tlie University of Pennsylvania there are two long, narrow tanks situated on each side of the door. The brine is ntit ]>umi)ed from these, but they simply act as a reservoir for cold brine. At the University of P)ufl'alo there are two long, shallow brine tanks, which are susjiendod, covering the whole top of the vault. The advantage in this 'arrangement is that the large mass of chilled brine cools the air above; this falls to the bottom of the vault replacing the warmer and lighter air there, and in this way a constant circulation is kept up (Figs. 1, 3 and 3).

Besides the expansion pipes in the brine, there is a considerable amount of pipe in the vault to cool the air directly. The arrangement of ammonia expansion coils is usually


things and the aim should be to get the insulation as jierfect as possible. Willi a perfect insulation there will be al)solutely no loss of cold and a temperature once obtained will be retained indefinitely. Of course a perfect insulation cannot be secured, but a little extra expense in the construction of the vault at the start is a saving in the end, as the machine will have to be in operation for a much shorter time. The illustrations show the method of insulation employed at the University of Pennsylvania and the University of Buffalo. These consist of a number of dead air spaces se])arated by boards and building, or tar pajier. Some of these air spaces may be iilled with cork or mineral wool. With the considerable changes in temperature and consequent expansion and contraction the insulation is liable to be destroyed. This may be partly overcome by having around' the outside a strongly braced wall, or one of brick or stone, as at the University of Pennsylvania and the University of Buffalo. It is


April-Mat-Junjj, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


121


important that the Audi- sIkuiIJ lie well insulated and covered on tlio inside with a layer ot Portland cement, asphalt or, better still, sheet zinc, which should extend up for a toot or so on the side walls of the vault. It is desirable also tluit the floor should slope toward the entrance, so that wlien the machine is shut down and the vault is being cleaned, the water will flow through the door to a drain placed in the room outside.

With a vault of a given size the capacity in bodies varies according to the method of storing them. There are three methods in general use in the different universities. The most popular is to have the vault arranged with a series of shelves. This is the method employed at the Universities of Buffalo, Pennsylvania, Syracuse and Long Island College Hospital. At the Johns Hopkins the bodies were first stored on shelves but in order to increase the capacity of the vault the shelves were removed and the bodies piled one upon an


^


c


JaL


J^




JK


(( m


UL


ifQ


^


"r


"T


Fiii. 7. — Side of vault showiiiiic the arrangement of the expansion pipes at the University of Kiiti'alo.

other. At Columbia and Cornell, N. Y., they are suspended. There are certain advantages in each system. The method of shelving the l)odics-takes up the most room, but it has the advantage that each body is easily accessible. The shelves may be divided into sections and each shelf numbered, then when a body is placed in the vault the record of its position can be added to the department history and it can readily be found when desired for a particular purpose. In actual practice tliis works out very nicely, as employed at the University of Pennsylvania, and a body which has been stored for months and is then claimed by relatives is easily located. The slielves may be either made of slats or solid boards. The latter are used at the University of Buffalo. AVIiere the subjects are piled one upon the other there are several advantages as well as disadvantages. First of all there is great economy of space, and the subjects being packed closely tend to prevent evaporation, but on the other hand there is a tendency for the bodies to become frozen together, causing considerable annoyance when one is to be removed. This


has been overcome by Dr. JInll liy placing a layer ol' building lathe between the bodies after they have been vaselined and wrapped. Of course in a great pile of bodies it is very difficult to find any particular one. Bodies packed in this way tend to hold the cold for some time, so after the machine is shut down and the vault thrown open it takes several days for them to thaw out. If these bodies are piled closely around a brine tank it is still more difficult to thaw them with the additional cold from the tank, and this is a great advantage in case of a break-down.

At Columbia and at Cornell, N. Y., the bodies are suspended and run into the cold storage vaidt on tracks like the carcasses at a slaughter-house. I do not know the advantages and disadvantages of this method.

The temperature in the vault should not be allowed to run .above freezing, as this permits thawing, and in consequence a slopj)y condition of the floor. The average maximum temperature usually maintained at the University of Pennsylvania is 24 degrees and the minimum 16 degrees Fahrenheit, and at the University of Buffalo the maximum is 2.5 degrees and the minimum li degrees Fahrenheit. This is computed from (he daily temperatures for June, July and August, 1899. which are given in the appended table. These temperatures are taken at the University of Buffalo by an ordinary thermometer, it being necessary to enter the vault to take the readings. At the University of Pennsylvania a self-recording thermometer takes the temperature variations.

All of the vaults are lighted by electricity, which may be turiuHl on by a switch from the outside Ijefore entering the vault. The cost of operating a plant varies greatly, depending on the size, number of hours a day it is run, number of subjects, and also the motive pow'er.

Steam is employed to operate the machine at the Johns Hopkins and at the Long Island College Hospital, and steam with electricity as reserve at Syracuse University. Electricity alone is used at the University of Pennsylvania, and a gas engine at the University of Buffalo. As the steam is also used for heating and the electricity for lighting it is difficult to estimate the exact amount of either used for running the machine. At the University of Buffalo and at the Johns Hopkins an estimate of the cost for one year was below $100.

In all the cases before the body is placed in the cold room it is endialmed and the arteries filled with colored plaster, starch or at the Johns Hopkins with shellac. When wanted the body has only to be taken from the vault to the dissecting room and upon thawing it is ready for work. When a body is kept in cold storage for a time there is considerable drying of the hands and feet, face and genitals, and when kept for a long time there is a general mummification of the body. To overcome this the body is covered at tlie Johns Hopkins with a layer of vaseline, over which is wrapped a layer of toilet paper, and the whole is covered with cheese-cloth. The same method is employed at the University of Pennsylvania. At the University of Buffalo and at Syracuse L^uiversity only the head, limbs and genitals are w-rapped.

Although there are other methods of preserving the body


122


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


for dissection, it would seem that a well embalmed body properly wrapped and kept in cold storage furnishes the cleanest, best preserved and most satisfactory dissecting material. Besides being used to preserve cadavers the refrigerating plants in the different medical schools are used to keep such material from the slaughter-house as is used for dissection. Fresh organs from post mortems are also preserved^ in the vault until wanted, or a sepai-ate compartment, cooled by the same machine, is built to contain them.

From the study of the various cold storage apparatuses for the preservation of anatomical material it appears that the system at the Johns Hopkins is the most economical, as it does not require continuous operation of the machine. This system is further improved at the ITnivcrsity of Pennsylvania and at the University of Buffalo for the direct system of cooling the vault at the same time the brine tank within the vault is chilled makes the pumping of brine unnecessary.

TABLES OF RESULTS OBTAINED DURING JUNE, JULY AND AUGUST, 1899 AT THE UNIVERSITY OF BUFFALO.

The machiue was operated only durins; the day, the uumbers below 13 are A. M., and those after 13 are P. M. The temperature is given in degrees Fahrenheit.






Maximum



M inimura


Date.


Duration of Run.


Time.


Temp.


Time.


Temp.


i899.







June 1


4 hrs.


10



24°


1


16°


3


3


10



33


1


14


3


3)4


9



22


13


13 •


4


3


9



26


13


16


.5


2%


9



24


13


14


6


3


9



24


13


14


7


3


9



24


13


14


8


2%


9.


15


34


13


14


9


2%


9.


15


34


13


15


10


4


s'



33


13


13


11


Sunday.






1


12


ax


8.


45


28


13


17


13


2Ji


8.


45


26


11


13


14


3


9



26


13


16


15


3)i


8.


50


26


13


Ifi


16


3


8.


45


26


13


16


17


43^


8



24


11


13


18


Sunday.







19


3


9



29


13


17


20


3X


9



36


13


16


21


SH


ii



25


13


17


23


SH


9



36


13


17


33


SM


9



34


13


14


24


3


8



34


13


14


25


Sunday.







26


3


9



30


13


19


37


3


8



38


13


16


38


3M


8



36


11


15


29


4


8



36


13


15


30


Engine out of order.







July 1


4K


8



31


13


14


2


Sunday.







3


iJ


8



31


{"


18 13


4


Holiday.







5


4


8



28


13


18


6


3%


8



26


13


16


7


4M


8



26


13


16


8


4%


8



25


13


15


9


Sunday.







10


3


8



30


11


18


11


3K


8



27


11


16


12


3M


8



26


13


15


13


3M


8



27


13


15





Maximum



Minimum


Date.


Duration of Run.


Time.


Temp.


Time.


'I'cmp.


1899.







Julvl4


3% hrs.


8


34°


13


1.5°


15


i'A


8


35


13


15


16


Sunday.






17


3>^


8


39


13


17


18


3K


8


38


11


17


19


iH


8


36


12


15


20


4


8


34


12


14


31


SH


8


34


11


17


32


4


8


35


13


14


23


Sunday.






24


4


8


39


13


18


25


3K


8


38


13


16


36


3}^


8


36


13


14


27


3M


8


36


13


16


38


3%


8


36


13


15


29


4


8


34


13


13


30


. Sundaj'.






31


sx


8


38


11


18


Aug. 1


4


8


37


13


17


2


4


8


36


13


15


3


3H


8


34


11


14


4


iX


8


35


13


17


5


4


8


35


13


13


6


Sunday.






7


4


8


38


12


16


8


3?i


8


36


13


15


9


3%


8


35


11


15


10


4


8


35


13


13


11


4M


8


34


1


13


13


4X


8


23


13


10


13


Sunday.






14


■m


8


38


13


16


15


4


8


36


13


15


16


3%


8


34


13


14


17


3/2


8


34


11


13


18


4J^


8


33


13


13


19


4


8


33


13


10


30


Sunday.






31


4


8


36


13


15


23


4


8


35


13


15


33


4X


8


33


12


13


34


3%


8


23


13


13


35


3%


8


23


11


12


26


3 'A


8


33


12


13


37


Sunday.






28


3%


8


37


13


17


29


4


8


35


13


16


30


'A

8


25


13


14


31


^•A


8


• 34


13


12


TEMPERATURE RECORD ANATOMICAL VAULT MEDICAL DEPARTMENT UNIVERSITY OF PENNSYLVANIA.

The temperature is given in degrees Fahrenheit.


Date.


Dumtion of Run.


Maximum Temp.


Mitiimnm Temp.


1900.

Aug. 26 37 38 29 30 31

Sept. 1

3

4 5 6

7 8 9 10 11 12 13


8 hrs.




13


9


4


10


10


3


10


10


5


9


11


5K


8


11


8


11


Vi


6


10


14


8


11


U}i


7


10


i-^K


6K


10


12}^


8


9


13}^


9


10


13>^


8


9


13


9


8


14


8


7


14


11


10


15J^


10


10


15j^


10.4


9


15;^


9


Apeil-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


123


Date.


Duration of Run.


Maximum Minimum




Temperatubi


IN Degrees Fahrenheit.






Temp. Temp.


Date.


/6u









tside.


Brine



Vault^








1900.














14

1.5


.5 hrs.

8

6



14i.3° 7°

13 7

14 9


1893.



A.M.


P. M. A


M. P


M.


A.M.


P.M.


Duration of Run.


Hi











17




15 15;^


November


21..






26


38


hours


IS


15



16 8



22..


. 60





29




19


13



n ^'A



23..


. 63





31




ao


10



9 5>^



24 .









21


9



13j^ 10



25..


. 62


73


oo


10


33


25


8


O'i


7



16 10^



26..


. 73


78


13


2


28


23


8


33


9



16 9



27. .


. 70


76


8


2


25


22


8


24


9



15 12



28..









2.5


8



16 9



29..


. 60


69


13


4


26


22


8


2B


8



15 8J^



30..


. 70


76


9



24


21


6


27


8



14>^ 9 14-^ 8


December


1. .









3S


10




2


. . 64


76


12



36


31


7


29


19



13|^ 1 1



S.. 4.. 5. .


. 63 . . 56 .. 57


,68 57 64


8


2


24

27 28


30 26 29


8








The above table was compiled from five discs, loaned by Prof. Piersol, on which the temperature was recorded aiito


6. .

7 . . 8 .


. . 56

. . 5S


63 64




29 30


30 31




iiiatically. Each disc recoi miiiibcr of hours during wh


ded a icb tb


week's temperature. The c machine was in operation



9. . 10. . 11..


. . 60 .. 58 . . 59


66 67 70


25 11


8 1


32 32 26


32 23 27



8 8


(by electricity)


was estimated fro


n the interval between the



12.. 13. .


. . 60 59


64 63




28 29


39 30




rii^e and fall o


■ the tempei


ature


curve. There is an incon


14.'.


. . .58


63




30


31



stant interval, after the machine lias stopped, during which tlie temperature does not rise appreciably. This was esti


1.5. . 16.. 17..


'.. 49 . . 68


48 78


20


8


32 32


32 24



8


iimtcd to be aliont one liour


and h


as lieen deducted in makino


IS. .


.. 70


78


8


2


29


20


s







19. .


. . 70


69




29


29



(lie above tabk






20 . 21..


.. 68 .. 67


68 69




30

33


31 33



TE.Ml'EKATURK


RECORD OF


THE BRINE AND VAULT AT THE


ON THE DEVELOPMENT OF THE NUCLEI PONTIS DURING THE SECOND AND THIRD MONTHS OF EMBRYONIC LIFE

Long M. On the development of the nuclei pontis during the second and third months of embryonic life. (1901) Johns Hopkins Hospital Bulletin 12: 123-126.

By Margaret Long.

[From the Aiiatojitii'iil Laboralori/ of Johna Ih'pkiita Vnu'erxitij.)


This work was undertaken in the fall of 1899 at the suggestion of Doctor Barker, and has been carried out with his assistance. The specimens used are human embryos and were very kindly lent by Doctor Mall from bis collection.'

' The numbers of the embryos correspond with their numbers in the embryological cabinet of the Anatomical Laboratory of tlie .lohns Hopliins University.


The following emljryos are described in the order of their probable age, as estimated by their length and by the develojiment in the rliombencepbalon. The arrangement of the cerebral nerves and the general appearance of the medulla oblongata agree with the His models and with the description given l)y His in "Die Entwicklung des menscblicben Kautenhirns"; a description of these is accordingly unnecessary. Each embryo has been studied in serial sections and from tliese sections a few, at different stages of development,. have been selected as characteristic of the structure of the pons, its nuclei and fibres. To make the work complete it will be necessary to study more embryos at intermediate stages between the five given here, and others from the third montli up to the adult ))ons.

Embryo No. LXXV is 30 mm. long and has been cut into serial sagittal sections. The nuclei, whiuli I have designated as " B," " C," " D," " E " and " H " in the various sections, are masses of cells distributed through the ventral part of the mantle layer (Mantelsehicht of His) at or near the level of the pontal flexure. The most medial of these nuclei extend to within 0.7 mm. of the middle line. An unstained fibre bundle can he .seen on the surface of the rhombencephalon ventral to the mantle layer throughout its entire lengtli.

Section No. 73 is 2.1 mm. to the left of the middle line (Fig. 1). Near the ventral surface on the cerebral side o.f the nervus trigeminus is a well defined cell-mass, '" B.' On the ventral surface opposite the nervus acusticus is a deeply stained cell-mass, " IT," which (wlien followed in the series) is seen to extend lateralward and spinalward to the floor of the fourth ventricle at the Junction of the latter with the telachorioidea. The section of the mantle layer presents longitudinal striations which have a slight ventral convexity. A few of these strands are more deeply stained than th.e rest between the level of the N. trigeminus and that of the N. acusticus. The dark ependymal epithelium and the unstained ventral fibre bundle are evident.

Section No. 91 is 1.2 mm. to the left of the middle line. On the ventral surface of the pons is a delicate shell or mass of cells, " H," continuous lateralward with " H " of the previous section. Between it and the mantle layer is the ventral fibre bundle. Dorsal from " A " is a cell-mass, " C," partially subdivided by a few colorless dorsoventral stripes; ventralward and cerebralward from " C " is another mass, " D," and still more cerebralward and dorsalward are two small deeply stained cellular masses, " E." The mantle layer of the medulla oblongata is deeply stained. It contains a diamond-shaped mass, " S," spinalward from " C," the longitudinal striations mentioned in the previous section, and an unstained dorsal filire bundle (DF).

Section No. 96 is 1.05 mm. to the left of the middle line. "H" and "C" are still present. The ventral fibre bimdle passes partly along the dorsal surface of "H" and partly between " C " and " E." Just cerebralward from the pontal flexure, close to the floor of the ventricle, is " M, an oval mass of cells witli a clear unstained area behind at its spinal end, and measuring 0.8 mm. in transverse diameter. The appearance of the mantle layer is the same as before. In its dorsal and cerebral part is seen an unstained dorsal fibre bundle.

Embryo No. LXXXVI is 30 mm. long and has been cut into serial coronal sections. There is ventralward a definite mass which I have designated as the nucleus pontis ventralis; it is about 1 mm. long by 3 mm. wide. The raphe enters


this nucleus in the middle line. Dorsal from its lateral part are several scattered masses which 1 have designated, tentatively, the nuclei pontis dorsales. The unstained ventral fibre bundle is dorsal from the nucleus pontis ventralis.

Section No. 175 is spinalward from the masses mentioned. On the ventral surface medialward from the nervus acusticus (-A^.l ) is the cell-mass " H." Followed through the series this cell-mass extends spinalward, dorsalward and lateralward to the ependymal epitlu^lium of the fourth ventricle; cerebralward, it is medial to the nervus trigeminus and continuous with the nucleus pontis. Taken in order from the raphe lateralward in the mantle layer are the nucleus olivaris superior (8) and the superior olivary complex {S}, the ascending and descending parts of the root of the nervus facialis, the nucleus nervi facialis {NNP), and the corpus restiforme {OR). On the floor of the fourth ventricle are the nucleus nervi abducentis (NNA) and the nucleus N. vestibuli (radicis deseendentis), {III? I'D); further lateralward are the nuclei N. cochleae, namely the nucleus N. eochleffi dorsnlis (NRCD) and the nucleus N. cochlea; ventralis (NNCV). The unstained area is the ventral fibre bundle (I'-P') Section No. 184 is 0.45 mm. cerebralward from the preceding section. In the mantle layer are seen in order the nucleus olivaris superior, (S), the nucleus nervi facialis (NNF). and parts of the ascending and descending limbs of the nervus facialis. "H" is on the ventral surface lateral from tlie nervus facialis. On the floor of the fourth ventricle is the nucleus N. vestibuli medialis et radicis descendentis (NNV).

Section No. 202 is 0.9 mm. cereliralward from section 184. The nucleus pontis ventralis reaches lateralward as far as the nervus trigeminus. In the middle line the raphe extends from the nucleus pontis to the ependymal epithelium. The nuclei pontis dorsales consist of several irregular masses, " A," " B," " C," and " E," and a more ventral and lateral mass. " D." These nuclei extend through the pons for a distance of 0.5 mm. in the cerebrospinal diameter. Between these ventral and dorsal nuclei is the unstained ventral fibre bundle. Lateral from the nervus trigeminus are the nucleus nervus trigeminus ascendcns and an unstained area.

Embryo No. XLV is 28 mm. long, and has been cut in serial sections, which divide the pons in an oblique direction in the following way: Instead of corresponding to the transverse diameter of the pons the left side of each section is further spinalward than the right side of the same section. The ventrodor.sal plane of the section is also oblique, so that in each section the left half of the dorsal surface is the more lateral, but in the right half of the pons the dorsal surface is more medial than the ventral. In other words, the first section removes a small portion of the pons about the cerebral ventral corner on the left side, and at the dorsal-spinnl angle on the right side.

The nucleus pontis, as seen in this series, is on the surface of the rhombencephalon and follows the curve of the pontal flexure so that it is crescentic in shape, with a ventral convex surface and cerebral and spinal ends or horns. Consequently.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXI.


G.V.



B


VF - H.


NT.



Fig. 1. — Section through the pous of erabrj'o LXXV, oO mm. lous; X 1.5 diameters.


Fig. 3. — Section No. 91 of embryo LXXV, x 1.5 diameters.



N.N.K. N.N.V



NRC.D


■M.R.C V CR.


Fig. 3.— Section No. 90 of embryo LXXV.


v.r. 5 s.


Fig. 4. — Section No. 17.5 tlirougli tlic brain of embryo LXXXVI, oO mm. long, x 15 diameters.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXII.


N.NV.



-.c R.


"N.N.F


s s.


N,F.



R— V


Fig. 5. — Sectiou No. 1.S4 throuirb embryo LXXXVI.


^f- N.PV,

Fig. (i,— Sectiou No. 302 througb embryo LXXXVI


N.P.D



N.PD. S


Fig. 7. — Section No. KIO tbrounb embryo XLV, x lo duimeters.


N.PD N.RYV. F: - N.PD



-C

-C.R.


.H.


N.A.


Fig. S.— Section 142 tbrougb embryo XLV.


Fig. i). — Sectiou 14.5 tbrouffb embryo XLV.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXIII.



'\


Fig. 10. — Section No. 92 tUrougb embryo XCV.



-^^^^


Fig. 11.— Section No. lUO tlirough embryo XCV.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXIV.


y? ./"^


jaSo?^y?^






^S



/


5.


"i


./-"'"


y




ill


^m^


//


Fig. 13.— .Section No. UIC. tUronsli eniliryo XCV.


TC-


HM-—-i


Fig. 13.— Section No. lOS through embryo XCV.


Apetl-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


125


the following sections may have a ventrocerebral, a ventral, a veutrospinal and a dorsal edge.

The nucleus pontis ventralis is a solid mass of cells continuous with the raphe. The nucleus pontis dorsalis ia divided into right and left halves not continuous in the middle line. The ventral fibre bundle passes between the ventral and dorsal nuclei except at their extreme lateral parts, where the cerebral ends of the two nuclei are united.

Section No. 13G is 0.05 mm. to the right of the middle line. On the right side the nucleus pontis ventralis is separated from the raphe by the ventral liljre bundle and nucleus extends across the middle line. On the left side the two ends of the nucleus pontis dorsalis are separated from the rajiho by the ventral fibre bundle and mantle layer. On the veutrospinal surface at the level of the nervus facialis is a deeply stained mass of cells, " H." This mass is continuous opposite the nervus trigeminus with the nucleus pontis; spinalward, dorsalward and lateralward it extends to the ventricular epithelium of the medulla oblongata. In the medulla is a cell-mass, " T," on the medial side of the corpus restiforme. and reaching from the fourth ventricle to the ventrospinal surface. Between " T " and the nucleus pontis dorsalis is a small round mass, " S," a little more deeply stained than the rest of the mantle layer.

Section No. 143 is 3.5 mm. to the left of the middle line and shows only the left side of the pons. Between the nuclei pontis is the ventral fibre bundle. The nucleus pontis dorsalis is in the mantle layer; in its spinal end is a small unstained space. On the ventrospinal surface is the uuiss " H." Medial from the corpus restiforme is a round, deeply stained area " S." Near the fourth ventricle are several dark masses just like those in section 136.

Section No. 145 is 0.4 mm. to the left of the middle line. The nuclei pontis ventralis and dorsalis are continuous at their cerebral ends. Between them is the ventral fibre bundle. Opposite the radi.x N. cochleae is " H," and median from it a cylindrical-shaped area. Between the cerebellum and the pons is an unstained area, the corpus restiforme.

Embryo No. XCV is 46 mm. long and cut into serial sagittal sections. The nucleus pontis is a solid mass of cells on the ventral surface of the pons, which has increased in size and measures 3 mm. in cerebrospinal, 4.6 mm. in transverse, and 0.5 mm. in ventrodorsal diameter. The ventral fibre bundle divides into two masses, the larger passes dorsal to the nucleus, the smaller through it.

Section No. 93 is 0.3 mm. to the left of the middle line. The nucleus pontis is a solid nuiss of cells. Dorsal from it is a dark wedge-sluiped area; its ventral surface reaches as far as the nucleus pontis and extends 0.4 mm. beyond the middle line on each side, the dorsal surface is continuous with tlie ependymal epithelium in the middle line and for a distance ol 0.3 mm. to the right. This area contains ventrodorsal markings, and small masses of cells staining more deeply than the rest of the tissue of the wedge between them. On the floor of the fourth ventricle just cerebral from the pontal flexure are two dark round cell-masses, " M," which extend through


a few sectjons on either side of the middle line, but in the middle line are overlapped by the greatly thickened ependymal ejiitlielium. On the ventral surface of the medulla oblongata is the ventral fibre bundle. Near the dorsal surface cerebral from the pontal flexure is the dorsal fibre liundle. The mantle layer contains the curved longitudinal striatiou, and in the isthmus is more deei)ly stained than in the medulla, and also contains blood-spaces. Next the epen(lynuil cpitlielium the mantle layer of the medulla [iresents a unit'onn appearance, and in the isthnuis it contains several darker masses ol' cells.

Section No. lOO is 0.6 mm. to the right of the middle line. The s]>iiwl portion of the nucleus pontis is divided into ventral and dor.^al parts by a clear area, containing a few dark strands com}iosed of cells. " M is still present; between it and the nucleus pontis are several small cell-masses. The ventral fibre bundle is on the surface of the medulla and next the dorsal side of the nucleus pontis. The mantle layer contains the curved longitudinal striatiou and blood-spaces. Between the dorsal fibie bundle and the ependymal epithelium arc numerous dark cell-masses.

Section No. 106 is 1 mm. right of the middle line. The nucleus pontis is more unevenly stained. Its cerebral end is divided into ventral and dorsal parts by an unstained area, which is continuous with the ventral fibre bundle. The fibre bundle extends the entire length of this section. It is now seen that this fibre bundle has an oblique direction through the cerebrolateral and spinomedial portion of the rhombencephalon. The appearance of the mantle layer is the same as in the preceding section; between the nucleus pontis and the nucleus olivaris a foAV of tlie curved striations are more deeply stained than the rest, S."

Section No. 108 is 1.4 mm. to the left of the middle line. The nucleus pontis is a smaller mass, unevenly stained owing to the presence of large numbers of white spots (nerve-fibres). Dorsal from it is the ventral fibre himdle. The mantle layer appeal's as before but the mass " M " is not present. Between the nucleus pontis and the nucleus olivaris are a few small cell-masses, and several more are scattered throughout the mantle layer of the isthmus.

Embryo No. XCYI is 48 mm. long and cut into serial sagittal sections. The nucleus pontis has increased in the ventrodorsal diameter. The appearance of this specimen is almost identical with that of No. XCV, and is only of interest because it corroborates what was found there. So I have not thought it necessary to add illustrations. Just spinal from the nervus trigeminus the nucleus pontis is continuous with a mass of cells which reaches to the ependymal epithelium of the fourth ventricle. The ventral fibre bundle passes partly along the dorsal surface of the nucleus pontis and partly through it. Among the latter fibres are a few scattered strands of cells resembling more the appearance of the pons at later stage. The wedged-shaped area and the cell-mass appear as before.

The histological structure of these specimens is as follows: The ependymal epithelium contains large, dark, densely


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[Nos. 121-122-123.


packed, round and oval cells. The mantle layer in the earlier stages consists of round cells and a few oval cells. In embryo No. LXXV an unstained fibrous network is seen and the round cells are scattered through it, which in No. LXXXVI and No. XLV are more closely packed together. In the older specimens neuroblasts of the mantle layer point in various directions, a good many of them direct their axones ventralward, and many roimd cells are still seen. Most of the neurolilasts are now arranged in definite groups; between them is an unstained fibrous network which contains spongioblasts. Both the nucleus pontis and the mass " M " are composed of round cells in all the sections. The mass " H " consists of round cells, resembling in size and staining reaction those of the ependynial epithelium. The raphe appears in two specimens; it consists of filjres which interlace across the middle line, round cells, ami in the frontal sections a few oval cells with their long axis transversely directed. In sagittal sections the raphe is not seen; its fibres, if present, would be cut in cross-sections.

Summary.

The main nucleus pontis is situated on the ventral surface of the rhombencephalon at the level of the pontal flexure. In the specimens the nuclei pontis are first seen on the surface


and in the ventral part of the mantle layer of the lateral part of the pons Varolii. Ventral to all, in this early stage, except the mass of cells " H," is the ventral fibre bundle. In the second embryo the nucleus pontis ventralis extends across the middle line of the rhombencephalon and the nuclei pontis dorsales are separated from its lateral part by the ventral fibre bundle. The nuclei pontis dorsales next form two solid masses, reaching almost to the middle line. They are still separated by the ventral fibre bundle from the niicleus pontis ventralis, except at the extreme lateral ends, where they are continuous with each other. Next the nucleus pontis becomes a solid shell on the ventral surface cut by a .small branch from the ventral fibre bundle. After the sixth month the pons consists mainly of fibres and scattered groiips of cells which increase at the expense of the dorsal part of the nucleus, while a narrow ventral nucleus or eell-nuiss is left on the surface.

The neuroblasts of the pons are continuous with the epithelium of the floor of the fourth ventricle:

(1) By the cell-mass " H " at the lateral end of the nucleus pontis.

(2) By the round cells in the rajjhe.

(3) In the middle line by the neuroblast in tlie wedge, which connects both the ependymal epithelium and the cellmass " M " w ith tlie nucleus pontis.


THE ARCHITECTURE OF THE GALL-BLADDER.

By Mervin T. Sudler, Pn. D., M. D.,

Iiislruclor in Anaioniy, Johns Tloplins University.


During the past few years the development of the surgery of the gall-bladder and ducts has increased the interest in their finer anatomy, and various investigations have been undertaken in order to add to our knowledge in regard to their structure. The lymphatics and finer blood-supply, however, do not seem to have had the same attention as the musculature and nerve supply; and so this paper deals more with this part of its structure and its histology than those which have been carefully considered in other papers.

The results mentioned here were obtained for the most part by the use of the gall-bladders of dogs and pigs. They were used because of their suitability and the ease with which they could be obtained. A limited number from cats and beeves were used also. The results thus obtained from fresh material were verified or refuted upon human gallbladders as far as the limited supply and general bad condition of them allowed. Within a few hours after death the bile stains and macerates the tissues so that they are quite changed. The mucous membrane disappears entirely in from five to six hours after death; the nuclei and tissues under it refuse to stain, and it is impossiljle to obtain satisfactory results from any but the fresliest material. For the histology small pieces hardened, distended and contracted in saturated


corrosive sublimate solution yielded material that stained well and gave good pictures. For the connective-tissue elements the most striking picture was obtained by the use of Van Gieson's acid fuchsin and picric acid, but Weigert's elastic fibre stain furnished the most accurate and delicate picture. For the blood-vessels ordinary carmine gelatin mans and lamp-black or cinnabar gelatin mass were all that were necessary. For the lymphatics a saturated aqueous solution of Prussian-l)lue proved to Ije the best, notwithstanding a careful trial of a number of more complicated and presumably better masses.

The thickness of the wall of the gall-bladder varies according to its state of distention. In an adult human sul)ject it is from 5 lum. thick in a state of distention to 2 mm. in a state of contraction. The distended gall-bladder of a newborn infant is nearly J mm. thick. In the pig it may be from 5 to 3 mm. thick, and in a dog of medium size from \ mm. to 1^ mm. thick. The wall of the gall-bladder is made up of the following coats: 1. mucous; 2. fibro-muscular; 3. subserous and on the free part covered by peritoneum; 4. serous. The relative thickness of these coats can be seen in Fig. 0, wliieli sliows tlie gall-bladder of the dog contracted. The relations are essentially tlu' same in man as in the dog.


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The mucows layer is thrown into a series of folds from ^ to I mm. high in man. These folds of mucous membrane cover corresponding ridges of connective tissue of the fibromuscular layer and contain an exceptionally rich capillary network. The irregular spaces surrounded by these folds are much larger at the fundus than at the duodenal end of the gall-bladder. In man the measurements in the distended gall-bladder are 3 mm. X 5 mm. in the fundus and 1 mm. X i nim. or smaller near the beginning of the cystic duct. In the crypts formed by the folds solitary lymph follicles are found. These are more numerous in the dog than in the pig, and in this regard there seems to be a great deal of individual vaiiation. The mucous layer is composed of simple colunmar eiiitlielium, which rests upon an iucomjilete muscnlaris mucosa. In the dog these cells are from 25-43 />• thick. These cells seem to secrete a thick mucous material but no goblet cells are present. R. Virchow (1), in an article published in 1857, finds tine fat-drops in the ends of these cells of the gall-bladder and ducts during or just after the absorption of chyle. These droplets gradually became larger and worked toward the base of the cell. He thought this fat had been lost from the liver in the secretion of the bile and was again picked up by these cells. Nothing was seen in my preparations to suggest this. Granules were often seen in the outer end or near the base of the cells, but these gave no reactions for fat. Belonging also to the mucous layer were the tubular glands. These were beautifully shown in specimens stained in gold chloride. There are few of them in the dbg, but in the pig, and especially in the ox, they are quite numerous.

The fibro-muscnlar coat is composed of smooth muscle fibres and interlacing bands of connective tissue. The direction and arrangement of these fibres has been very carefully studied by Hendrickson (2). He concluded that in the gallbladder there are no definite layers and that the bundles of fibres interlace in all directions with the greatest number tending toward a transverse direction. According to Doyon (3), the muscle fibres arrange themselves in two methods in different animals: 1. A network with rather rounded meshes. This arrangement is found in the guinea-pig. This fact has been corroborated by Ranvier. 2. The muscle fil)res are arranged into bundles which form a number of principal directions more or less plainly marked out. This is found in the dog and cat, and means about the same as the description of Hendrickson. My preparations and sections lead me to agree with Hendrickson, with the possible exception that near the fundus in the dog there is an outer and rather definite longitudinal layer. See Fig. 0. The part of this layer near the mucous membrane is composed almost entirely of connective tissue with only a few muscle fibres scattered through it, the part directly under the epithelium forming a mucosa which, however, shades ofi: gradually and is not sharply separated from the underlying tissue. It is in this region that the thickest plexus of capillaries and intrinsic lymph channels exists. The solitary lymph follicles, to which reference has already been made, are found also here just


inider the mucous membrane. Toward the subserous layer, on the contrary, the muscle fibres are collected into well developed bundles (especially so in the pig and ox) and theconnective tissue is corresponding-ly less. Elastic tissue occurs even here, however, varying in form from fine threads to coarse bands. It is especially abundant in the neighborhood of the blood-vessels. See Fig. 6. Unstriped muscle also exists in the larger gall-ducts, and at the point where the ductus communis joins the ductus pancreaticus it becomes modified into a sphincter. This has been found by Hendrickson in man, the dog and the rabbit, and also by Helly (4) in man, and Oddi (5) in man. The fibro-mnscular layer contains the larger blood-vessels, which divide into branches and thus supply the other layers. See Figs. 2 and 6.

The subserous layer is composed of dense interwoven elastic tissue bands which contain comparatively few nuclei, and therefore few connective-tissue elements. These bands form an irregular mesh-work which is denser on the side toward the serous layer. This layer is poorly supplied with bloodvessels, although there is a well developed set of lymph channels which communicate with the large superficial vessels coming from the liver. By ])nlling the gall-bladder apart it is possible to divide it into two la3'ers; the separation occurring at the junction of the subserous and fibro-muscnlar layers. By separating injected tissues in this manner a very pretty picture of the circulation in each part can Ije obtained distinct from the other.

The serous layer is present only on the part covered by peritoneum, i. e. the fundus, the inferior surface of the gallbladder and the outer surface of the gall-ducts. If is composed of simple flat endothelial cells from 4-6 ," thick and adds but little strength to the organ. The larger lymphatic vessels from the liver and deeper layers of the gall-bladder nui between it and the subserous layer.

Brewer (G) has described in a very careful manner the way the cystic artery reaches the gall-bladder in man and the variations one would find ordinarily. He found that in 50 subjects only 3 corresponded to the type described in textbooks of anatomy. It is possible to judge from this of the great amount of variation existing in its blood-supply. The largest artery after it has reached the gall-liladder is usually found, however, on its inferior surface and on the side toward the middle line of the body. There also may be a smaller branch on the side away from the middle line. This is covered at first by peritoneum and then penetrates the outer part (if tlie fibro-muscnlar layer and gives off the branches which suj)ply the viscus. ]\Iost of tlie larger vessels are in the fibro-muscnlar layer near the dividing line between it and the subserous layer. See Fig. C. If the needle of a hypodermic syringe be introduced into one of the smaller arteries and llie mucous surface be watched while the fluid is slowly iujecti'd tlie arterioles and capillaries can be seen to be filled in areas about 2i mm. in diameter at a time from a single centrally placed artery. The capillaries under the mucous niemlirane are very niuuercnis and in the folds tlie capillary nclwdrk is especially lliick. See Fig. 2. The blood from


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[Nos. 121-122-133.


these is collected into the veins and returned to the larger and deeper lying ones accompanying the arteries.

The subserous layer has a comparatively poor blood-supply. The arteries are small and the capillaries widely separated. Some of the capillaries run out between this layer and the serous layer, and thus provide for the nourishment of the peritoneal covering. Some veins of considerable size are also found in this layer. On the surface of the gall-bladder in contact with the liver the veins communicate with the branches of the portal vein and the arteries in part come from the hepatic artery.

The large lymphatic vessels running over the gall-bladder bring lymph from the liver and the coats of the gall-bladder. They follow the inner side of the cystic duct and end in mesenteric lymph glands in the dog. In the pig and in man we have either one or two systems of the large lymph vessels. In almost all cases both are represented but the territory may not be equally large and there is wide variation in their method of distribution. In cross-section these vessels are always flattened although the degree of flattening varies with the completeness of the injection. Sappcy (7) figures a mass of them running over the gall-bladder in a manner somewhat resembling Fig. 4, but he only mentions the fact that they bring in the lymph from the liver and deeper layers of the gall-bladder. In my preparations they run down eventually on the inner side of the gall-bladder but there is usually a large vessel coming from the same side, but with the exception of one specimen figured in Plate 2, .Fig. 4, which was believed to be pathological, are not as numerous as shown by Sappey.

In the subserous layer there is a network of lymph channels which empty into these larger vessels. See Fig. 7. This network is very irregular and the lymph channels vary markedly in size and shape. The picture of these lymphatics which seemed most normal was obtained by injecting carmine gelatin into the portal vein at a pressure of 80 mm. of mercury for fifteen minutes. This injects the lymphatics of the liver and in turn the larger ones over the gall-bladder, and finally these in the subserous coat in a more or less complete manner, but without any tearing or stretching of the vessels. In Fig. 2 they are represented as though the greater part lie simply on top of the subserous layer, while, as a matter of fact, they are scattered through it rather evenly.

The submucous sets of lymphatics are in the connective tissue just under the mucous membrane. However, they rarely run u]) into the connective-tissue folds but are at their lowest part or more frequently just at their base. The network is almost entirely absent in the denser muscular part. These were best seen by injecting aqueous Prussian-blue slowly under the mucous membrane and the injected portion was afterwards fixed and studied. In some cleared specimens the lymphatic vessels could be seen running up and joining the more superficial lymphatics of the subserous layer or directly one of the large superficial vessels as shown in Fig. 1. The lymphatic tissue belonging to this layer has already been described.


The nerve supply of the gall-bladder has been studied by Dogiel (8) and Ilubor {'.)) within recent years. The nerve supply is derived from two sources, viz., 1. tiie sympathetic system of ganglia and fibres connecting them, and 2. raedullated fibres accompanying the large arteries. In regard to the distribution of the sympathetic fibres Huber suggests from the condition prevailing in other viscera that they supply the blood-vessels and smooth muscle of the coat. Doyon thinks these are unable to act without receiving stimuli indirectly from the great splanchnic nerve. Dogiel has figured in a beautiful manner the kinds of cells found in the sympathetic ganglia and concludes that all the varieties found in the walls of the intestines occur here also. Quite a number of medullated fibres are also found near the large arteries. Both Huber and Dogiel have noted them. The former suggests that they are sensory fibres and are distributed to the mucous membrane. Their termination, however, has not yet been settled by direct observation.

Eefehences.

(1) Rud. Virchow: " Ueber das Epithet dcr Gallenblase imd tiber einen intermediaren Stoffwechsel des Fettes." Virchow's Archiv, Bd. 11, H. 6, 1857.

(2) Wm. F. Hendrickson: "A study of the musculature of the entire extrahepatic biliary system, including that of the duodenal portion of the common bile-duct and of the sphincter." The Johns Hopkins Hospital Bulletin, vol. ix, 1898.

(3) Maurice Doyon: "Etude analytique des organs moteurs des voies biliares chez les vertebretes," These sc. nat. Paris, 1894. An abstract of this article in Lehrbuch der Vergleich. Mikros. Anat. der AVirbeltiere, Albert Oppol, Jena, 1900.

(4) K. K. Helly: " Die Schliessmuskulatur an den Miindungen des Gallon und dcr Pankreasgiinge." Arch. f. Mikros. Anat. Bd. 54, 1899.

(5) E. Oddi: " D'une disposition a sphincter speciale de I'ouverture du canal choledoque." Arch. Ital. de biol. T. 8, Fasc. 3.

(6) George Emerson Brewer: " Some observations upon the surgical anatomy of the gall-bladder and ducts." Contributions to the Science of Medicine by the Pupils of Wm. II. Welch, 1900.

(7) C. Sappey: Description des vaisseaux ]yui]ihatiques. Paris, 1885.

(8) A. S. Dogiel: Ueber den Ban der Ganglion in den Geflecthen des Darmes und der Gallenblase des Menschen und der Saiigethiere. Archiv f. Anat. u. Phys., 1899.

(9) G. Carl Huber: Observations on sensory nerve-fibres in visceral nerves, and on their modes of terminating. Journal of Comparative Neurology, vol. x, No. 2, 1900.

DESCRIPTION OF PLATES XXV-X.XVI.

Fro. 1. — Tlio <!;[in-bUi(lder of a pig; natural size. Tlie lymphatics were injected by placing the needle just under the peritoneal covering of the liver near the edge of the gall-bladder at (.V). The blurred mass in the centre represents the injection mass showing through and the


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXV.



THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXVI.




Fig. 4.


Fk:. h.



Fig. 6.



Fi(i.


Fig. S.


M. T. Suiller del.


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129


lymphatic vessel coming up from the deeper layer to join tlie large superficial one. X:= Needle of syringe.

Fig. 2. — Reconstruction of the wall of the partially contracted gallbladder of a dog, magniBed 60 times, showing the blood-vessels on the right and the lymphatic vessels on the left. Lymph follicles are shown on the right as two rounded eminences just under the epithelium. The vena comites shown is quite characteristic for the larger arteries. The large lymphatic vessel is shown partially collapsed.

Fio. 3. — Gall-bladder of adult man, showing superficial lymphatics. }4 natural size.

F[G. 4. — Gall-bladder of man 19 years old, dead of chronic nephritis, showing the large superficial lymphatics. This gall-bladder gave


evidence of having been through an inflammatory process, and so the lymphatics are probably abnormally numerous.

Fig. 5. — Gall-bladder of dog, showing the superficial lympliutic vessels. Natural size.

Fig. 6. — Section through the contracted gall-bladder of a dog, magnified 80 times, showing the arrangement into coats and the relations of the blood-vessels.

Fig. 7. — The lymphatics of the subserous layer of a dog. (Camera drawing.)

Fig. 8. — The lymphatics of the fibro-mnscnlar layer of a dog, showing their relation to the folds on its surface. These folds are represented narrower and less complicated than in the specimen in order not to hide the lymphatics. (Outlines made with the aid of a camera.)


REMARKABLE CASES OF HEREDITARY ANCHYLOSES, OR ABSENCE OF VARIOUS PHALANGEAL JOINTS, WITH DEFECTS OF THE LITTLE AND RING FINGERS.


By George Walker, M. D., Instructor in Surgery, Johns Hopkins Unircrsily.


Account.? of diverse abnormalities of the arms, forearms, hands, and feet, are to be found in literattire from the remotest medical history, and not a few books and monographs on these Yarious defects have appeared from time to time. Most of these reports comprise instances of polydactylism of various degrees; abnormal shapes of the metacarpal and phalangeal bones; absence of the jihalanges and carpal bones; increase in the number of the phalanges; absence of fingers; absence of the bones in the arm and forearm; abnormal sha]ies and lengths of the radius and ulna; lateral tminn of the jihalanges; union of the fingers by the soft parts, etc.

Two cases have recently come to my knowledge which have sufficient Ijearing on the ones herein reported to warrant a short synopsis of them in this paper.

The first was that of a child in which there was a lateral fusion of the first and second metacarpal bones of both feet. This was not supposed to be hereditary until the grandmother, upon examining her own foot, to show where the defect had occurred in the child, found her own bones in exactly the same condition. Although she was seventy years old, she had never previously noticed it.

The second case was that of a young girl whom I examined. There was a partial stiffening in tlie metacarpo-phalangeal articulation of the thumb; this was ligamentous, and not bony, and permitted a certain amount of motion, probably about one-half that of normal. This defect had occurred in one of her brothers, one uncle, her father and her grandfather. All of them were afl^icted in the same joint, and had about the same amount of motion.

The cases which I herewith report show either a complete bony ancliylosis or an absence of various Joints between the l>halanges, together with an absence of one or more bones of the little and ring fingers. As will be seen in the family tree, it has occurred in five generations. I have examined the cases so far as possible, and have made Koentgen photogra]ihs from four of them, thus representing two generations.

Thomas B. applied to the dispensary of the Johns Hopkins


Hospital for the treatment of leg ulcer. He was fifty-two years of age, well nourished and apparently well developed and healthy. On examination of his hands I found the thumb and index finger normal; in the ring and middle fingers nothing could be seen on inspection in the extended hand, contrary to the usual type, but on jialpation there was found an entire bony anchylosis of the second metacarpal joints of above fingers; the bony enlargements corresponding to the heads of the bones were present, and in the middle finger a distinct sulcus could be felt on the thumb side; other than this the enlargement was regular and smooth.- The terminal joints were negative. The little finger presented only two phalanges, there being, however, near the end of the first phalanx, a slight enlargement which possibly corresponded to a joint. The thumb was 7 cm. in length; first phalanx, 4 cm.; and second phalanx, 3 cm. The index finger, 8^ cm.; first phalanx, 3^ cm.; second, 3 cm.; third, 2^ cm. Middle finger, 9:^ cm.; first and second together, 7^ cm.; third, 1| cm. The first from basal joint to middle of enlargement, 4 cm.; the second, from middle of enlargement to distal joint, 3i cm. Ring finger, 9 cm.; first and second phalanges, 6-^ cm.; third, 2^ cm. Little finger, 6 cm.; first phalanx, 3} cm.; second, 2^ cm. The left hand presented nearly the same appearance, and on cai'cful palpation and measurement the only difference found was that in the little finger, first phalanx, there was a slight bowing, making a palmar concavity toward the end. This was due, according to the statement of the patient, to an old fracture. Tlu^ enlargement at this site, as is shown in Eoeutgen Photograph No. 1, is very much greater than ift the other hand, and suggests that it had probably i)een caused by trauma; in the other finger the enlargement can be seen, but to a much less degree, thu?? making it doubtful whether there is an obliterated joint, or the absence of the middle phalanx. The metacarpals were of normal length and their articulations were negative. The carpus was negative. The feet presented nothing abnormal, except a slight giving way of the arch. The other parts of


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the osseous s_ystem were well developed and did not differ from the usual types. The patient stated that the deformity gave him very little inconvenience, and did not interfere with his work. Both the above hands are shown in Eoentgen Photograph No. 1.

On being questioned in regard to his family history, he said that his father, grandfather and great-grandfather were similarly affected. The middle joints of all his father's fingers were stiff; the defect in the grandfather and great-grandfather was known to have existed, but the e.xact nature could not he determined. He had three uncles and one aunt; two of the uncles he thought were affected, but was not certain; the other uncle and aunt were free. In his immediate family there were four brothers and one sister. One brother and the sister had negative hands; the otber three brothers ])resented the family trait. He had four children, all of whom were free. His younger brother had had three cliildren, two dead and one living, none of whom were affected. His elder brother had eleven children; four of them, two boys and two girls, had the defect. I have visited and examined the two brothers and their families, and I give in the following a report of said examination.

Henry B., the younger brother of the above described, is a gardener, 48 years old; a strong, well built, healthy man; five feet eight inches in height and weighs 148 pounds. Both hands are affected. Right thumb, negative; length, 7 cm.; first phalanx, 4 cm.; second phalanx, 3 cm. Index linger, length, G| cm.; first and second, 5 cm.; third. If cm.; the first Joint is normal, second is stiff, distinct bony enlargement at site of joint, slight sulcns on thumb side. Middle finger, 2^ cm.; first and second phalanges, 7^ cm.; third, 2 cm.; first from basal joint to middle of enlargement, 4^ cm.; first joint is negative, the second is stiff with rounded, smooth, bony enlargement; no sulci. Ring finger, 8| cm.; first and second, 6| cm.; third, 3 cm.; first joint is negative, second anehylosed, bony enlargement not so marked. Little finger, 5^ cm.; first and second, 3f cm.; third, 1^ cm.; the first joint completely stiff, second negative, metacarpal bones and carpus negative. Other hand presented same appearance and nearly the same measurement. Feet and remainder of bones in the body did not differ from normal.

William B., elder brother, very strong, hale, robust man, 58 years of age, 5 feet 11 inches in height, weighed 172 pounds. Both hands affected, as shown in Eoentgen Photograph No. 2. Middle joint, ring and middle finger and both joints in little finger stiff. Thumb and index finger normal, remainder show absence of middle joints. Length of thumb,

7 cm.; first phalanx, 4i cm.; second phalanx, 2^ cm. Index.

8 cm.; first phalanx, 3| cm.; second, 3 cm.; and third, H cm. Joints all negative. Middle finger, 9^- cm.; first and second phalanges, 7i cm.; third, 2 cm. The first joint completely anehylosed, distinct thickening at joint site, with small depression. Ring finger, 9 cm.; first and second, 7 cm.; third, 2 cm.; first joint site presents nsual bony enlargement, but no joint was present; second joint negative. Little finger, 5i cm.; slight palmar concavity, comjilcte anchylosis of lintli


joints; 1^ cm. from the end there is a slight enlargement with furrow in middle at joint site, but no motion; the first joint is also completely immobile. The metacarpals are normal in length, size and articulation; the carpus is negative. The left hand does not differ in essential characteristics from the one described. The feet presented no abnormality.

The patient stated that he had worked at the same bench with two men for fifteen years, and they had never noticed the defect. He had eleven children in his family, four of whom were affected; the others had perfect hands.

I have seen most of the children of the above described, and the following is the condition of the four wlio are affected.

Sallie B., aged seventeen, rather poorly developed, tall ami slim, height five feet six inches, weight 115 pounds, both hands affected, as shown in Roentgen Photograph No. 3. Thumb and index, free; right hand, thumb, 6 cm.; first phalanx, 3|- cm.; second phalanx, 2^ cm.; joint normal. Index finger, 7 cm.; first phalanx, 3 cm.; second, 2| cm.'; third. If cm.; both joints negative. Middle finger, 8^ cm.; first and second, 6| cm.; third, 2 cm.; complete anchylosis fir.st joint, second joint is negative. Ring finger is represented only by the first plialanx, which is 4 cm. in lengtli. The distal end is slightly enlarged, and tapers towards middle finger. The little finger is represented also by only first phalanx, 3| cm. in length. It presents same shape of enlargement at distal end as ring finger. The left hand is the same as right, except that- the middle joint of the index finger is anehylosed. In these hands, notably in the left one, there is a distinct crowding together of the metacarpals, being most marked in the fifth, which, as shown in the photograph, decidedly overlaps the fourth. The carpi are negative; the remainder of bones apparently normal. The feet were not examined, but according to the statement of the patient they presented no abnormalities.

Carrie B., aged fifteen, rather strong and robust, weight one hundred and seventeen, five feet four inches in height. I was unable to procure a photograph of this hand on account of the unwillingness of the patient. Both hands are affected, and very similar to those of her sister, as above described. Right hand, thumb and index finger, normal. Ring and little fingers of both hands, as in the case of her sister, present only one phalanx, that of the ring finger is 4 cm. in length, and that of the little, 3 cm.; the distal ends are slightly enlarged, and according to palpation are like her sister's. In the other hand the index finger is anehylosed at the middle joint, and the middle finger presents a striking peculiarity in that the anchylosis is in the second joint, the first being free.

Henry B., a picture of whose hand I was unable to obtain, but upon examination found the following conditions:

Not very robiTst, tall and slim, age fifteen; height five feet six inches, weight one hundred and twenty pounds, both hands affected. Index and thumb in both negative, remainder affected. Thumb, right, 5| cm.; first phalanx, 3 cm.; second phalanx, 2| cm.; joint negative. Inde.x, 7| em.; first phalan.x, 3 em.; second, 2^ cm.; third, 2 cm.; phalanges normal in size, and ioints negative. T\Tiddle finger, 8.', cm.; first and second


April-May-Junk, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


131


]ihalanges, 6^ cm.; third, 2^ cm.; first joint is stiff with distinct bony enlargement, and slight depression between heads of bones; second joint is negative. Ring finger, 8 cm.; first and second, 6 cm.; third, 2 cm.; first joint is anchylosed, second is negative. Little finger, 5^ cm.; first phalanx, 4 cm.-, middle is absent; the third, 1| cm. There seems to lie an entire absence of the second phalanx; the first is normal and presents no enlargement which might correspond to a joint. The left hand differs in one particular from the above described, in that the terminal phalanx of the little finger is turned inward toward the ring finger, and forms an angle of 135 degrees with the second phalanx. The metacarpals and carpi are negative. The remainder of the bones present no defects.

George B., aged seventeen, height five feet six inches, weight one hundred and fifteen jiounds, rather poorly developed, slightly anemic. J'>oth hands shown in Roentgen Photograph No. 4. Right hand, thumb, G cm.; first phalanx. '■Vj cm.; second, 2} cm., joint, normal. Index finger, 7 cm.; first and second, 4^ cm.; third, 2^- cm.; first joint site shows normal enlargement, but is stiff; second is negative. Middle finger, 8 cm.; first and second, G cm.; third, 2 cm.; first joint completely anchylosed; second, negative. Ring finger, TJ cm.; first and second, 5-i cm.; third, 2 cm.; first joint stiff; second, negative. Very slight enlargement at first joint site. Little finger, 5 cm.; first, S^ cm.; second, absent; third, l-J- cm. .Iiiint is negative; first phalanx is normal in length and shajK'. (liei'e Ijeing no enlargement nor anything to suggest an anchylosed joint. Jletacarpals and carpi negative. The other lianil [iresented the same apiiearance. The remainder of the liiidy negative.

In ]ienising the literature bearing on these subjects, I have round only a few similar cases reiioi'ted, none of them being so marked as mine, and only one was hereditary.

Klausner, in a rather exhaustive monograph on various deformities of the arm and band, reports a case in which the anchylosis was present in the second phalangeal joint of the index finger; the hand was very much deformed otherwise, aiul the fingers partly webbed. There was no hereditary history, nor were any other members of the family so affected.

Wolf, very recently, has put on record an anchylosis of the second phalangeal joint of the little finger. In this case the middle phalanx was very much shortened and was joined to the first by a bony union at an angle of about 14.'J degrees. The terminal phalanx was apparently normal. This anchylosis had occurred in four generations, and was in-esent in eight instances. Some of them were inherited from the father and others from the mother. The same joint of the same finger was affected in every case; the remainder of the hand was normal; there is no record of any other defects in the body; the condition of the pectoral muscles is not mentioned. The fingers in the cases of both Klausner and Wolf are shown by Roentgen photographs.

E. Stintzing reports a case of a very much deformed hand in which there was an almost complete anchylosis in the second joint and partial in the first. In this case the fingers


were webbed; a diminution in the leUgth of several of the nuddle phalanges and a defect in the right pectoralis major muscle.

J. Sklovowski relates an instance of a defect of the sternum, pectoralis major and minor muscles, and a portion of the back muscles, together with an absence of the second, phalanx in the second and third fingers; a shortening of the other ])halanges, and a limitation of movement in nearly all of the phalangeal joints, with a complete anchylosis of both joints in the fourth finger.

Hoffman describes a deformity occurring in a man 48 years of age, in which there was a stiffening in one or more lihalangcal joints, and a shortening of the middle phalanx of the middle finger. In the index finger the middle phalanx was small and completely fused with the third [ibalanx. There was also webbing of the finger?, associated with muscular defects in the chest and back muscles.

Fuerst gives an accurate account of a hand whieli was examined after death by a very careful dissection. In this hand there was great shortening and malformation of the middle phalanx of the middle and ring fingers. There was no anchylosis in any. In all of the above cases, with the exception of the last, the observations have been made on the living subject, and usimlly by palpation alone.

With the exception of the two girls in the ])resent generation of the cases which I herewith report, none of the females have heretofore been affected, and in them appeared the only instances in which the terminal phalanges were absent. There is another striking difference in one of them, as is shown in the Roentgen Photograph No. 2, in the partial overlapping of the fifth metacarpal bone, which suggests the )iossibility that continued transmission might produce a fusion, or an absence of one of these bones.

From the above it will be seen that the defects have existi'd in five generations, and have been confined entirely to the hands, the i-eniaining osseous system pi-esenting no peculiarities. Except in the )u-esent generation the hands have been otherwise nornuil. The first dejiarture from this was in the case of the boy. Roentgen Photograph No. 4, where there isau absence of the middle phalanx of the little finger; while in both of the girls, as is shown in one by the Roentgen Photograph No. 3, the end and the middle phalanges of the middle and ring fingers are absent. There is also a partial obliteration of the distal enlargement of the remaining phalanges.

By a study of the photographs, one can see that there is undoubtedly a bony union and not a filn-ous anchylosis in the joint sites. The enlargements corresponding to the heads of the bones are plainly to be seen and felt, but the joints arc absolutely unformed. In a number, small sulci could be palpated, corresponding to the normal depression between the heads of the bones. The jihotographs also show that there is a certain porosity at the joint sites, which seems to be more than normal.

The question arises whether these are cases of entire absence of the joints, or of early anchylosis. The two phalanges are about the normal length, and there is a distinct enlarge


132


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


uioiit coiTospoiuling to the metacarpiil lioads, with small sulci between some of them, but other than this there is no evidence whatever of an attempted Joint formation. In view of the fact of a complete bony union, it appears best to consider them as cases of an absence of the joint rather than of an anchylosis. It has been suggested that probably the ancliylosis may have occurred after birth as the result of some disease; but according to the statements of the motliers of these various children, it was a congenital defect. A careful examination of the other bones failed to show any abnormal conditions or diseases, and the history of lues was not present.

The examination of the arm shows a fairly good muscular development, and so far as could be made out there was no atrophy of the flexor sublimis digitorum. The muscles of the hand were also well developed and the thenar and the hypothenar eminences were apparently normal. There was an exception to this in the hand of the girls, where there was found a rather poor development of the hand muscles, which was most notably marked at the hypothenar eminence.

The palmar folds in the hand were normal, but in the skin over the anehylosed joints they had become nearly smoothed out; the two normal croasings being scarcely discernible.

The epiphyses were all joined; which was unfortunate as otherwise some light might have been thrown on .the bony development.

In nearly all of the reported cases there have been defects in the back and breast muscles; the most striking examples of which were found in the pectoral region. The cases which I herewith report presented no such abnormality, and showed upon examination a completely developed condition of the muscles of the arm, shoulder and back. In all the instances the feet were negative.

These cases are in striking contrast to the generally accepted opinion that deformities of the hands and feet arc transmitted by the mother, for in each of those in this series it came through the father, the mothers having all been normal. It is most interesting to note that in each generation only one male member has transmitted the deformity to his offspring.

The occupations of tlic individuals were very little interfered with; the only inability complained of was that of being unable to grasp small articles with the whole hand. The deformity, except in the cases of the two girls, was not at all striking, and unless one carefully inspected the hands it would be overlooked, and even in shaking hands it was not noticeable.

Shortening of the Phalanges.

In my cases, as well as in most of the above-reported ones. there has been a decided shortening of one or more of tlic phalanges. It has been in nearly every instance most stiikingly observed in the middle phalanx with a certain predilection for the little finger.

In discussing such cases, Fuerst states that in nearly all of these defects the shortening is seen in the middle phalanx. and he ascriljes it to the fact that in embryologic development the middle phalanx is the last to become bony. This


occurs when the embryo is about 8 centimeters in lengtli. and he thinks that at this period the deformity commences. From observations of his case, and a study of certain others, he concludes tluit the shortening and anchylosis are stages in fusion of the first ajid second bones. The shortening represents the first stage; the anchylosis the second stage, and the whole phalanx the third stage.

Tliis theory does not seem to be based upon sufficient observation, nor is there enough evidence in the studied cases to justify any such assumption.

In my cases, as is shown in tbc photograjihs, there is no shortening at all in the ]ihalanges of the second and third fingers, although a com])lete anchylosis exists; this would stand directly against the theory which Fuerst has advanced. In the little finger, however, there is some evidence for the liypothcsis, for in the second generation there is present a diminution in the phalanx, then an anchylosis, and finally, in the case of the boy, the joint has entirely disappeared, and there remain only two normal phalanges.

A very distinct and decidedly unique type, so far as the above-mentioned cases are concerned, is to be seen in the hand of the girl; for in this case the end and middle phalanges have entirely disappeared, and have left the first phalanx only partially developed. The diminution and absence of the end phalanx were not noted in the other reported cases, and can not be explained on the ground of the late bony development.

The little finger first shows a beginning defect, and in the case of Thomas B., Eocntgen Photogi'aph No. 1, left hand, the first phalanx is long, somewhat curved, and presents a slight enlargement which probably corresponds to a joint site. The middle phalanx then will be represented by a small bone about H cm. in length. In the case of the nephew there are certainly only two phalanges; and in each of the girls only one is present, and the defect has extended to the ring finger.

Thanks are due to Dr. Finney for ]iermi.ssion to re])iirt these cases. I am also indebted to Professor W. A. S. HamUK^l for the care which he gave to the preparation of the photographs.

Literature.

Wolf: Ifucnchener niedicinische Wochenschrift, Mai '21), 1900, No. 22.

R. Stintzing: Dcr angeborene und crworbene Defect dcr Rrustmuskeln, zugleich ein klinischcr Beitrag zur progrcssivcn Muskelatrophie. Deutsches Archiv fiir klinische Mcdicin, 15 Bd., 1889.

J. Sklodowski: ITebcr cineu Fall vtm angeborencin I'echtsseitigem Mangel der M. pectoralis major et minor uiit gleichzeitigen Missbildungcn der rechtcn Hand. Archiv fttipath. Anat., etc., von E. Virchow, Bd. 121, 1890, 1.

Hoffman: Ein Fall von angeborenem Brustmuskeldefect niit Atrophic des Amies und Schwimmhautbildung. Virchow's Archiv, Bd. IIH, 189fi, S. 163.

Fuerst: Zeitschrift fiir Morphologic und Anthropologic. Band II, Heft 1, 1900.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL-MAY-JUNE, 1901.


PLATE XXVII.



Fig. 1.



Fig. 2.


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXVIII.



Fig. :!.



Fio. i.


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


133


Thomas B., Known to be aflectt-d.

Charles B., son.

Known to be utt'ected.

Exact condition unknown.


Charles B., (iraudsuu. Unknown.


John B., Grandson.

Both hands, middle joint,

all tinners.


Susan B.,

Granddaughter.

UnalTected.


C'HAiiLES B., Grandson. Unknown.


William B.,

Great-trrandson : Both hands, rintt, middle and little lingers. First joint.

Sallie B., I

Great-jrreat-granddaui; liter. Both hands, inde.x and middle linger. King and little linger, one i)halan.\ only.

Carkie B.,

(i reat-great-granddaughter. Both hands; middle linger, tirst and second joint, right hand. Iude.\ and middle, Urst joint, left hand. Ring and little linger, one phalanx.

George B.,

Great-great-grandson. Botli hands, inde.x, ring and middle fingei, first joint;

ihsenee phalanx middle linger. Henry B,, Great-great-grandsou. lioth hands, ring, middle and little linger, tirst joint.

Joseph B., UnalTected.

Caleb B., Unallected.

Edith B., Unatl'ected.

George B., Unaffected.

JOSEI'II B.,

Unaffected.

Susan B., Unaffected.

Charles B., Unaffected.


Thomas B,,

Great-grandson.

Both hands, ring,

middle and little linger.

Middle joint.

Jennie B., Unaffected.

Marv B., Unaffected.

John B., Unaffected.

William B.,

Unaffected.


Henry B., Great-grandson. Both hands, middle and ring linger. Middle joint.

Charles B., Unaffected.

Joseph B., Unaffected.

Margaret B., Unaffected.


NOTE ON THE BASEMENT MEMBRANES OF THE TUBULES OF THE KIDNEY

By Kr.vnki.in P. Mall. Professor of Analomij, Johns Hopkins Universily.


In au earlier jmMication upon reticulated t).«sues in general tlie statement wns made that the whole framework of tlie kidney, including the lja.sement membranes, from the capsule to the pelvis, is formed by one mass of anastomosing fibrils, and that the sliarp borders of the librils mark the outlines


of the tubules to form the basement membranes which in ordinary sections i!]ipear to be homogeneous.' This statement was based upon observations made by digesting frozen


' Mall, Abhandl. dcr math.-phys. classe dcr Kiiiiigl. Siicli. (iesehell. der wisscusch., Bd. Ill, and Johns Iloiikius Hospital Reports, vol. 1.

sections of the kidney, digested in pancreatin, stained with acid fuchsin and differentiated with picric acid. By this method all of the cells and other structnres of the kidney are destroyed, leaving only the white fibres and reticulated fibrils which are stained intensely red. This observation has been confirmed by Eiihle," who used a method similar to the one I employed. Eiihle digested small blocks of kidney (after hardening in alcohol) with pancreatin until all the cells were dissolved, then made sections in paraffin, which were stained irpon the slide. By this method the topography of the reticulum is retained much better than is the case in specimens made by the freezing method.



Fig. 1. — Longitudinal section of the fr.imewoik encircling a kidney tubule digested in pancreatin, stained witli acid fuchsin, and differentiated with picric acid. Enlarged 'SiS times.

The work of Eiihle, which is very accurate and extensive, shows quite conclusively that the fibrils obtained by his method, as well as by the freezing method, are identical with those which form the interstitial tissue as seen in ordinary sections.

The observations given above have been confirmed by Disse,' who states, however, that the basement membranes of the kidney which have been isolated by means of strong acids always appear to be homogeneous. This he explains by as.suming that pancreatic digestion resolves the membrane into fibrils by dissolving the cement substance between them. The strong acids, however, dissolve the interstitial connective


tissue but do not affect those fibrils which are stuck together by the cement substance to form basement membranes.

Von Ebner' is of the opinion that the iibrillar a])pearance of the basement membranes of the kidney is due to fine folds in it owing to the method of preparation. He further states that the fibrils of connective tissue between the tubules stain with acid fuchsin while the membranes do not. There is some truth in this statement, for in sections of the kidney which have been macerated and slightly tinged the stained fibres shine through the homogeneous membrane, often making it ajipcar folded. Yet with some care the true nature of these makings is easily determined.


-lUihle, His's. Archiv, iS'.l".

3 Disse, Sitzungsbericlite dcr Gescliellsch. zur Beforderung der gesanimten Naturwisseuschaftcn zu Marburg, November, 1898.



Fig. :.'.— Transverse section of the rcticulura encircling a kidney tubule prepared as Fig. 1.

Keceiilly, while studying sections of the fresh kidney liy m{>ans of various methods, I obtained specimens which ]n-oved that tlie ol)servations of Eiihle, Disse and myself are correct, so far as they go, but that our conclusions regarding the basement membranes are not correct. The baskets, which I reproduce in Figs. 1 and 2, do exist, are easily obtained by means of pancreatic digestion, but do not form the basement membranes. An additional membrane, the basement membrane, lies within this tube and is totally destroyed by means of pancreatic digestion. The most instructive specimens I obtained were made by macerating frozen sections of the rabbit's kidney in a cold saturated solution of bicarbonate of soda for a number of days, after which most of the cells have been converted into a slimy mass. Shaking the section vigorously in water soon cleared the framework, wliicli was next spread upon a slide and examined. In case most of the cell remnants had been removed the section was dried upon the slide, stained with acid fuchsin, differentiated with picric


■• Von Ebner, Kolliker's Handbuch der Gewebelehre, Bd. 3, S. 374-375.


April-May-JuxNU, IIJOI.J


JOHNS HOPKINS HOSPITAL liULLETIN.


135


acid and numiite'd in halsani. Suceossful sections prepared in this way sliow the basement membranes partly filled with the remnants of epithelial cells, the interstitial reticidatcd connective tissue and the blood-vessels. A portion of such a specimen is shown in Fig. 3.

After specimens of the basement membranes and the rcticuhim are obtained through maceration in bicarbonate of soda, as described aliove, they may be treated with various reagents to test their projierties. Dilute solutions of IICl and KOI I cause the reticulum to swell and become transparent, whili' the basement mendjrane and the elastic filjrils accompanying the arteries remain unchanged. But it is shown by the Weigert's elastic tissue stain that the mem])ranes are not elastic, for they do not take on the stain wliile the elastic tissue fibres do. Furthermore, Mallory's connective tissue stain,° stains the reticulum but not the membranes. As far as I have tested the basement membranes they give reactions


^ Mallory, Journal of Exitcriniental Mi'tliciiiu, vol.


much like the membranes of elastic fibres, but whether they arc identical with them I have been unable to determine.



Fig. 3. Lon</;itu(linal section of a kidney tubule with the surrouudinK

reticulum from a specimen macerated in bicarbonate of soda for a week, shaken, dried upon the slide, stained with acid fuchsiu and dill'erentiated with picric acid. The basement membrane partly tilled with broken epithelial cells and surrounded with reticulum are shown. The drawingis semidiaijrammatic.


A COMPARATIVE STUDY OF THE DEVELOPMENT OF THE GENERATIVE TRACT

IN TERMITES/

By H. McK. Kxower, Ph.D., Inslrnclor in Anaioniij. Johns Hopkins Univcrsiiij.


Tiie facts here prescnled furnish a mure accurate guide in estimating the status of individuals in the communit} Hum has been hitherto available. Xew light is thrown on hypotheses as to the possible inlluence of workers and soldiers in the transmission of hereditary characters in these communities. These studies will also be seen to bear on jiroblems of the comparative morphology of the sexual organs of insects. Six species of two genera (Calotermcs and Termes) were investigated.

The efferent passages and accessory glands of Termites are simple, as in Thysanura. In Termes flavipes they arise first in larvs just hatched, in which the mesodermic duct from ovary or testis ends blindly against the ectoderm of the hypodermis. In the female three separate and segmental, unpaired invaginations of the ectoderm appear, one behind another on the ventral mid-line. The pouch of the anterior segment comes into contact with the mesodermic oviducts, that of the next segment later becomes the receptaculum seminis, while the posterior invagination bifurcates at its inner end and eventually forms the colleterial glands. In larva? preceding those evidently destined to become workers and soldiers, and in adult workers and soldiers, this disconnected segmental condition persists (Fig. 1). In other word.s, the workers and soldiers exhibit a peculiar arrested,


' A preliminary abstract presented to the American Morphological Society, December, lUOO.


larval stage in the dcvelopmcul u£ the sexual ap|iaraUis. In older larvaB of sexual individuals the three, segmental, independent rudiments telescope together and unite to form a vaginal canal with colleterial glands, reccptaculum seminis, and mesodermic oviducts opening into it. In the male there



Ov.il.j-ct.

Rectft. 5e«>. c:<.U.slo«A.


Fio. 1. — Modilied camera sketch of ventral aspect of tip of abdomen of Termes flavipes, adult worker or soldier. Female.

is a single median ectoderinic invagination into which the j)aired, mesodermic vesicuhe semiuales, and vasa deferentia, eventually open (Fig. 2). In adult workers and soldiers of this sex an arrested larval type is exhibited in the sexual apparatus.

Modifications of this history occur in i)tlier siiecies, affecting workers and soldiers especially.


136


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nog. 131-123-123.


In a species of Eutermes from Jamaica the most extreme inodiflcation is found. Not even rudiments of the cctodermic passage and accessory glands a])pear in Avorlscrs or soldiers (Nasuti) of this species. The origin of the ectodermic apparatus of sexual individuals of this species is, however, essentially that of the corresponding structures of flavipes.



SfiUicU.


Fig. 3. — Similar sketch of adult worker or soldier. Male.

The condition of the mesodermic sexual gonads, male and female, is very simjjle in a Jamaican species of Calotermes, a primitive genus of the group. In advanced larvae and in soldiers the ovary is a series of egg-tubes opening into the


oviducts, while the testis is composed of the same number of tulmles or follicles arranged serially on the vas deferens.

In T. flavipes and in the Jamaican Eutennes the youngest larvffi exhibit a condition similar to that in Calotermes, which arrangement, it will be observed, Ijears a suggestive resemblance to the type found in Thysanura.

In the Jamaican Eutermes the workers and soldiers exhibit an extreme arrest of the development of the gonads, which do not proceed beyond the stage found in the youngest larva just hatched.

The adult workers and soldiers of a Japanese species of Termes. unlike T. flavipes, possess gonads not greatly modified from the serial type which seems to be primitive.

In T. flavipes the gonads of older larvre and of adult workers and soldiers in both sexes lose this priinitive type: the tubules of the testicle, for instance, becoming twisted into a globular mass in which the original serial order is obscured.

The gonads of larvae of sexual individuals, in all species studied, change from the condition at hatching to a type in which the simpler original arrangement is much obscured.

Additional facts with suitable discussions will be published shortly, fully illustrated.


A COMPOSITE STUDY OF THE AXILLARY ARTERY IN MAN.

By J. M. HiTZEOT.

{From the Anaiotnli'al Lahorotory of the Johns Hopkins University.)


At the suggestion of Dr. Mall the following records were made from dissections in the Anatomical Laboratory of the Johns Hopkins University during 1898-99 and 1899-1900. Charts' were furnished the students with the request that they draw the axillary artery with its branches, etc., as found in their subjects, giving as nearly as possible the origin and distribution of each branch and maintaining the relation to the pectoralis minor and the various bony structures of the axillary region. The charts were merely outlines of the skeleton upon which each student sketched his dissection. When this sketch was finished it was added to or changed Ijy the writer, so that the sketch might, as nearly as jiossible, represent the artery as it existed in each dissection. Parallel with these drawings a set of not€s was kept in which the constant and the unusual branches of the artery were carefully noted. During the year 1898-99, considerable difficulty was experienced with the terms short thoracic, acromio-thoracic, etc., the student in his eagerness to apply these terms to the different branches often overlooking the more important feature, i. e., the distribution of the branch. To obviate this to some extent the charts of this year were compiled and the composite picture thus obtained was drawn and furnished as a guide for the future. The terms before mentioned were kept but special stress was laid upon the origin and distribu


1 Bardeen, Outline Record Charts used in the Anatomical Laboratory of the Johns Hopkins University, Johns Hopkins Press, Baltimore, 1900.


tion of the artery. The results thus obtained were uniformly more satisfactory than those of the previous year.

The charts used in the following tabulations are less than a third of the total number made. The remainder, because of errors in drawing, broken arteries in dissecting, and discrepancies between the notes of the writer and the sketches, were omitted. These omitted charts, in so far as they were of any value, gave jiractically the same results as were obtained from the tabulation of the coiTcct and more complete charts. In making the tabulations the arbitrary divisions given by the various anatomists were used.

Part I, that portion of the artery extending fi(nn the lower border of the first rib to the ujiper border of the ]iectoralis minor.

Part II, that portion of the artery which is beneath the pectoralis minor.

Part III, that portion of the artery which extends from the lower border of the pectoralis minor to the lower border of the tendons of the teres major and latissimus dorsi.

During the first tabulation separate tables were made for the right and left sides to determine whether the origin and distribution differed on the two sides. As the only dift'erence found was in the presence or absence of the long thoracic artery this distinction was dropped, the relative dift'erence consisting in the more constant presence of the long thoracic artery on the left side.


Apeii^May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


137


The charts themselves conveniently fall into different types, that i.-;. the artery in a certain number of instances gives oif its lij'anches from the same divisions of tlie arterial trunk and these brandies are distributed to tlie same regions. The ti' charts here taimlated fall into 7 types, type I being present in 20 cases; type II in 9 casjs; type III in 7 cases; type IV in 4 cases; type V in 3 cases; and tyi>es VI, VII each in 2 cases.

Type I (Fig. 1 and Table I).

This type, the most constant found in the laboratory during the two years the dissections were observed, differs from the text-book descriptions by the absence of the long thoracic artery. The area ordinarily supplied by this artery, accord


FiG. 1. — Type I of the axillary artery. Present 30 times in 47 cases.

.1, Ramus acromialis ; a, Ramus ascendens; AC, A. circumflexa humeri anterior; b, M. biceps; C, R. clavicularis ; eb, M. coraco-brachialis; D, M. deltoideus; <l, Ramus anastomotieus; DH, A. eireumflexa, scapukr, (dorsal scapular); LB, il. latissimus dorsi; P, R. pectoralis; PC, A. circumtlexa humeri posterioris; PM, M. pectoralis major; pm, M. pectoralis minor; .S', A. subscapularis ; s, M. subscapularis; SM, M. Serratus anterior (magnns); .S'P, A. profunda bracliii, (superior profunda); T\ A. thoracalis suprema ; T-, A. thoraco-acromialis ; T ■', A. thoracalis lateralis; TM, M. teres major; 1, 2, 3, 4, 5, 1st, 3d, 3d, 4th and .5th intercostal spaces.

ing to te.vt-books, being supplied by liranches from the acromio-thoracic and subscapular arteries. The branches in this type can be conveniently arranged in the following schema: I

( 1. Superior thoracic.


Part 1.


Part II.


Part III.


Acromio-thoracic.


No branches. 1. Subscapular.


(■ 1. Thoracic branch.

I 3. Acromio-hnmeral branch. l_ 3. Clavicular.


C 1. Dorsal scapular.

I 3. Muscular branches.

] 3. Anterior.

[ 4. Posterior.


., , . . . „ ( Ascending branch.

3. Anterior circumflex. .; , . ",. ( Anastomotic.


o. Posterior circumflex. 4. Muscular branches.


( Muscular. \ Anastomotic.

iCoraeo-brachialis. Biceps.


The superior thoracic (A. thoracalis suprema) rises just below subclavius muscle and crosses the first inters]iace, ending in it and in the second interspace. The origin of the artery is remarkalily constant in this type (19 times in 20 cases), it supjilies the muscles in the first and second interspaces.

The acromio-thoracic (A. thoraco-acromialis) rises from Part I. about midway between the clavicle and upper border of the pectoralis minor, runs almost directly anteriorly and divides into the (1) thoracic branch, (2) the acromio-humeral and (3) clavicular branch.

This artery is the most constant in this type, being present in ail 20 cases. The thoracic branch turns downward beneatli the pectoralis minor, giving off branch to the pectoralis major and minor, and to the second and third intercostal spaces and the overlying skin. The acromio-humeral branch runs upward and outward across the costo-coracoid membrane over the coracoid process of the scapula and gives a branch to the acromion and accompanying the cejihalic vein between the deltoid and pectoralis major breaks into branches, supplying these two muscles and the snrnuinding fascia and skin. The clavicular branch is a small branch which turns upward to sujiply the subclavius muscle.

Tlie subscapular artery arises from the axillary trunk at the lower border of the subscapularis muscle and takes a downward and inward course through the axilla. Near its origin it gives off a branch to the subscapular muscle and a large branch, the dorsal scajiular, which passes through the triangular space formed iiy the subsca]iularis, teres major and long head of the triceps, to the dorsum of the scapula, sup]ilying the muscles of that region. A small branch to the teres major muscle then comes from the subscapular trunk as it crosses that miscle, and before it splits into the thoracic iir anterior branch and its posterior or muscular branch. The thoracic branch crosses the base of the axilla from the back to the front and supplies the serratus magnus, the fourth and fifth interspaces, and the adjacent skin. The posterior branch continues the downward and backward course of the subscapular trunk tn end in the serratus magnus, and the latissimus dorsi, giving off numerous branches to these muscles.

Two small muscle branches are given oft' to the coracobrachialis and biceps.

From the anterior portion of the axillai'y trunk a small artery, the anterior circumflex, rises, passes beneath the coraco-brachialis aJid biceps and sends a branch to the joint by way of the bicipital groove and a branch around the arm to anastomose with the posterior circumflex artery. In its course it gives otf brandies to the overlying muscles. At aiiout the same level and from the posterior portion of the axillary artery the posterior circumflex takes its origin, passes downward and backward through the space bounded by the teres minor, long head of the triceps, teres major and the humerus, winds around the neck of the humerus, supplying the deltoid, the joint, the triceps, and the adjacent skin


138


JOHNS HOPKINS HOSPITAL BULLETIN.


[No.s. 121-123-123.


iml anastomoses with the anturior circumflex artery and bufierior profunda artery.

Type II (Fig. 3 and Table II).

Tlie braiulics in type II are conveniently arranged according to the following plan:


C Superior tlioracic.


Parti.


] Acromio-tluiracic.

L

Part II. j Long tboracic.


!1. Thoracic braucli. 2. Acromio-lnimeral 1 o. Clavicular braucli.


branch.


Part III.


Subscapular.


C 1. Dorsal scapular. I 2. Muscular branches.


1^ 3. Posterior branch.

». , ( Anterior circumtlex. Trunk. - „ , • • „

^ Posterior eircumfle.x.


This type ditl'er.'; fmni tyiie 1 only by the presence of a branch from the part II of the axillary trunk and corresponds



Fig. 3. — Type II of the axillary artery. Present '.) times in 47 cases.

with the description of the axillary artery usually given in the text-books. This branch from the second part of the artery bears the name long thoracic (A. thoracalis lateralis). It takes its origin beneath the pectoralis minor, courses downward along the lower border of this muscle, supplying it, the serratus magnus, and the third, fourth and fifth interspaces. In its course it gives off small branches to the fascia of the axilla, and terminal branches which piercing the pectoralis major terminate in the overlying skin. The other arterial branches have the same origin and distribution as described in type I, except that the intercostal areas of the thoracic branch of the acromio-thoracic artery and the thoracic branch of the subscajnilar artery are replaced wholly or in part by this branch from part II. The anterior and posterior circumflex arteries arise by a common trunk but otherwise their course and distribution correspond to the description gi-ven under type I.


Type 111 (Fig. 3 and Tai;le III).


Part I.


f Superior thorjicic

I

J

! .\cromio-th'_'racic.


Thoracic br. A croniio- humeral. Clavicular. C I. Thoracic branch. I 3. Muscular branches. I H. Posterior circumflex. "j 4. Dorsales scapulae. I r>. Anterior branch. [ G. Posterior " ( Ascending. .\nterior circumflex. I

( Anastomotic.


Part II. Subscapular


Part III


The branches from part I are similar in their origin and distribution to those described in type I. From part II a large subscajnilar artery takes its origin. It immediately gives off a l)ranch (tlioracic) which supplies the serratus magnus and crossing the axilla licmeath the pectoralis minor



Fig.


-Type III of the axillary artery. Present 7 times in 47 cases.


supplies that muscle and the second, third and fourth interspaces. Just above the lower border of the pectoralis minor a larger branch descends which gives off the posterior circumflex dorsal scapular, and muscular branches and terminates in an anterior branch to the fifth interspace and serratus and a posterior branch to latissimus dorsi and serratus. From the drawing and description the thoracic branch of this artery can be seen to correspond with the description of the " long thoracic " artery, while the lower descending branch corresponds to the description usually allotted to the subscapular artery. The artery, however, can lie Ijetter descriljed as the subscapular artery because, as is seen in type I, the subscapular artery does supply the mid-thoracic region and because the long thoracic artery is so often absent. The anterior circumflex has the same origin and distribution as that given it under type I.


Apeil-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


139


Type IV (Fig. 1 axd Table IV).

In type IV the aeromio-thoracic artery commonly fonnd in part I is foimd arising from part II of the axillary trnnk. The distribiition of the branches in this type is similar to that given nndor type I (the snperior thoracic supplying the



Fig. 4. — Type IV of tlie axillary artury. Present 4 times in 47 cases.

first interspace only), with an added lirancli to the subseapnlaris mnscle which, taking its origin from part I, turns backward and downward, passes between the trunks of the brachial plexus and ends in the subscapularis muscle.


( Superior thoracic. Part I. )

( Braneli to M. subscapularis f Tboi'aci

Part II. Aeromio-thoracic. '


i Clavicular. I Acromio-bunieral. ^ Acromial. (^ ( Muscular.

C ., , , , ( Coraco-bracliialis.

I Muscular branch. - „.

( Bleeps.

I pi. Muscular.

T, , „, ' , , , I 2. Dorsal scapular.

Part III. -; Subscapular. >,.,,,■

'^ ' 3. Anterior.

[_ 4. Posterior.

„ , ( Anterior circumllex. i Trunk. < r, , • [ (Posterior "


Type V (Fig. 5 and Table V).

From the table aud drawing it is readily seen that practically the wliole jiectoral area, the thoracic and subscapular regions, are supplied by an artery given off from part II of the axillary artery. From the table it will be noticed that this was the case twice, while in the third case two arteries with the same distribution as the above mentioned trunk have separate origins from the main trunk. In this latter case the origins of the two arteries supplying this whole area were so close together that for practical purposes they can bo called a common trunk and are incorporated as such in the drawing of tin's type. It is important, however, to re


member that type V may be represented by two branches rising close together from part II, as is seen by the drawing given for that type. In one ease the trunk had an even larger area of distribution than is shown in the drawing, the anterior and posterior circumflex regions being supplied by




3—


m


^


^^


sA



s

If


Fig. 5. — Type V of tlie axillary artery. Present "• tinics'iu 47 cases.

branches from the large trunk from part II. These two variations in type V are given because future research may show that one of these variations is more common than that found to be most frequent in my observations.


Part I.


Part II.


I Superior thoracic (small).

f c Thoracic branch.

. . ■ .1 • ! . ■ ( Clavicular.

1. Acromio-thoracic. J Acromio- \ . . ,

, , J. Acromial,

humeral. 1 ., [ ( Muscular.

2. Long thoracic.

[' Muscular.

., „ , , I Dorsal scapular.

i. subscapular. ■ . , • . ■

] Anterior branch.

[_ Posterior " Anterior circumflex.


Part III.


( Anterior ( Posterio


In the above schema I have called the branches by their adopted names, and the distribution of each branch from this trunk is similar to the distribution described under types I and II.

Type VI (Fig. G and Table VI).

This type existed but twice in the dissections observed and is remarkable for the number of branches wliicli ari.'^e from part I.


Part I.


f Superior thoracic. Aeromio-thoracic.


I Pectoral branch. Long tlioracic.


{Clavicular. Acromial. Deltoid. ( Muscular. ( Intercostal.


I


140


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


Part II. No branches, f Dorsal scapular.

r „ , , I Muscular.

Subscapular -(..., ,

I ^ ' Anterior branch.

,,. J l_ Posterior "


Part


j Trunk.


f Anterior circumflex. \ Posterior "

The superior thoracic is small, giving a twig to the upper digitations of the serratus and ends in the first interspace.



Fig. 6. — Type VI of the axillary artery. Present '2 times in 47 cases.

TIlis type shows to a marked degree a variation which occurs in the origin of the acroniio-thoracic artery, i. e. a separate origin of its pectoral or tlioracie branch, while the artery designated as the acromio-thoracic is merely the acromio-hunieral division of that artery. From the table it will be noticed (line 2, table VI) that tlie thoracic branch of the acromiothoracic artery was ]n-eseut in one case. My notes on this case mention the fact tliat this branch was extremely small and that the area usually completely supplied by it receives most of its blood-supply from a branch rising from the main trunk. This pectoral branch rises from the trunk slightly above or just adjacent to the origin of the acromio-thoracic artery, courses downward and forward, supplying the pectoralis major and minor and the second, third and fourth intercostal spaces. The long thoracic artery, except for its origin, is similar to that described under type II.

The subscapular artery is the same as that of type I, and the trunk common to anterior and posterior circumflex arteries is the same as that of type II.

Type VII (Fig. 7 and Tablk VII).

Type VII occurred but twice in the records made. In this type, as in type VI, the thoracic branch of the acromiohumeral artery is very small, being represented by a small twig to the pectoralis minor, while its area of distribution is supplied by a branch from the large subscapular artery; in type VI it was supplied by a separate branch from the axillary trunk.


[■ Acromio-thoracic.


Part I.


Part II.


I




Thoracic.

Clavicular.

Acromio-humeral.


Acromial. Muscular.


Pectoral.


Subscapular.


No branches.


j Upper division, j Lower " ■{ Muscular. ! Dorsal scapular.

Anterior division. 1 Posterior '*



1 >.


F:q. 7. — Type VII of the axillary artery. Present 2 times in 47 cases.


Part III. Trunlc.


C Muscular branch.

„ , ( Anterior circumflex. ■^ Trunk.


I


( Posterior Superior profunda.


In this type the superior thdracic is absent and its area of distrilnition is supplied by the suliscapular.

The cromio-thoracic is the same as type 1; while the thoracic or pectoral branch is small. The subscapular arises well above the upper border of the pectoralis minor, turns downward beneath that muscle and supplies the whole thoracic, pectoral and subscapular regions. Part III gives off a large trunk which runs parallel to the main artery, gives off branches to the eoraco-brachialis and biceps, and a trunk wliich immediately splits to form the anterior and posterior oircumtiex arteries (distribution similar to that under type I), and then turning down, out and back passes through the musculo-spiral groove to become the superior profunda artery.

In the first part of this paper the types into which the axillary artery fell are discussed and it is my intention in this portion to discuss the individual branches with their origin, distribution and variations.

Superior Thoracic. — This artery was remarkably constant, appearing 40 times in the 47 cases here tabulated. In the 7 cases in which it was absent it was supjilied by the acromiothoracic in 4 cases. This is the condition described as normal by Testut, Sappey and Cruveilhier. In 2 cases the subscapular supplied its area (type III), and in one case a large trunk from paxt II of the axillary (type V). The artery was most frequently distributed to the first and second interspaces,


Aphil-May-Jdne, 1901. J


JOHNS HOPKINS HOSPITAL BULLETIN.


141


as in type I. In 4 cases, however, the artery was distinctly longer than normal and rising high up in the axilla, turned directly downward and passed along the lateral thoracic wall, supplying the interspaces from 1 to 4 (in 2 cases the 5th also) and the serratus magnus muscle. This artery was in close relation to the posterior thoracic nerve, heing anterior to it and separated from it by an accompanying vein. As far as can he ascertained, this artery has not been described before. In one of these cases the artery was of considerable size and gave branches to the glandular contents of the axilla and sent numerous branches forward in the intercostal spaces. In some respects it corresponds to the long thoracic, hut owing to its presence in a case in which the long thoracic was present also, and its origin near that ascribed to the superior thoracic, it has been included in the description of the superior thoracic artery.

Acromio-tlwracic Artery. — This branch, the most constant of the axillary subdivisions, came from part I in 40 cases, from part II in 5 cases and in the remaining 2 cases came from the trunk common to it, the subscapular and long thoracic arteries (type V). For convenience of description the following schema of the acromio-thoracic artery will be found very useful.


Acromio-thorac


J Pectoral brai

ic. } Clavicular bi

^ Acromio-huE


Pectoral branch, branch, imeral brauch.


The pectoral branch of this artery was present 43 times in the 47 dissections. In the 4 cases in which it was absent its area of distribution was supplied by a pectoral branch from the axillary trunk in 3 cases (type VI), and in one case from the subscapular (type VII), which shows the thoracic branch present although small. This pectoral division of the acromio-thoracic trunk is very variable in size, occasionally beinglarge, in which case it supplies the pectoral muscles, the second to fifth interspaces, and the serratus magnus and latissimus dorsi. In those eases in which there is a long thoracic artery present, it is smaller than in the first instance and is limited to the pectoral muscles and the upper interspaces. Occasionally it is very 'small, being merely a muscular branch to the pectoral muscles, and its area in this case is more completely supplied by branches from the long thoracic, the subscapular or by pectoral branches from the main trunk.

The clavicular branch is a small artery which was present 43 times in the 47 dissections. In the 4 cases in which it is absent 3 cases show no artery to this area from any of the axillary subdivisions; in one case it was supplied by a branch from the main trunk. The acroniio-humeral branch is the most constant subdivision of the acromio-thoracic, and in those cases in which the pectoral branch is absent, it, with the clavicular branch, forms the acromio-thoracic artery. In the discussion of this subject under type VI, I have suggested that this artery is merely the acromio-humeral artery and not the acromio-thoracic, since it lacks the thoracic or pectoral portion. Its distribution is also constant. In one case the humeral or descending branch was small, the anterior cir


cumflex artery in this case being large and sending off large ascending branches to the deltoid and clavicular portion of the pectoralis major. In 3 cases a branch is given off to the subscapular muscle.

The Long Thoracic. — This artery was present only 11 times as a separate branch from the a:silla.ry trunk (types II and VI) and it was with this artery that the most trouble arose in tabulating the dissections. The 11 cases here tabulated represent a large majority of the number found in all the charts received. In discussing the question of the absence or presence of a major branch from part II. it is found that in 24 cases no major branch is found, while in 23 cases there is a major trunk.

Instances in which there are no arteries from part II, tyjie I, 20; type VI, 2; type VII, 2.

Instances in which there are arteries from part II, type II, 9; type III, 7; type IV, 4; type V, 3.

The cases in which the artery, arising from part II of the axillary is the long thoracic, axe, however, less frequent, that artery being present only in the 9 cases represented by type II.

The long thoracic artery, as described by His, arises beneath the pectoralis minor, courses downward upon the serratus magnus to the fifth or sixth interspace, supplying that muscle. The external mammary branches pierce the pectoralis major and supply the skin in the mammary region. According to Testut, it arises beneath the pectoralis minor, courses obliquely downward, inward and forward along the lateral thoracic wall between the pectoralis major and the serratus magnus as far as the fifth, sixth or seventh interspace, where it terminates in anastomosis with the intercostal arteries. As it descends it gives off numerous collateral branches to the axillary glands, the subscapular muscles, the serratus magnus, pectoralis major and minor, the intercostal spaces, the mammary gland, and the antero-lateral region of the thorax. According to Quain, the long thoracic artery arises beneath the pectoralis minor, is directed downwards and inwards along tlie lower border of that muscle and is distributed to the pectoral muscle, the serratus magnus, and the breast, forming anastomosis with the intercostal arteries.

From the above descriptions it is readily seen how variable the distribution of the artery may he. My cases correspond more nearly to the description given by Quain, although in 3 of the cases the artery corresponded with tlie description given it by Testut.

The Subscapular Artery. — This artery varied consideralily in its place of origin, coming from part I in 2 cases, from part II in 8 cases, from })art III in 35 cases, and in 2 cases from the trunk common to it, the long thoracic and acromiothoracic from part II. The common distribution of this artery is that given it under type I. It may, however, vary considerably, as is seen from the description given it in type III. In four cases the artery was small, being practically only the dorsal scapular artery. In these cases its remaining areas were supplied by the long thoracic in 3 cases, and by a large thoracic branch from tlic acromio-thoracic in one case.


142


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


(Sec table tj^pe I). The anterior and posterior circumflex areas are also supplied hy this artery, the former in 2 cases and tlie latter in 9 cases. In one case it also gave rise to tlie sujierior profunda artery. The cases in which the suliscapular included arteries usually arising from 'the axillary or brachial trunks can be classified as follows:

Subscapular -j- posterior circumflex and superior profunda.

Subscapular + posterior circumflex,

Subscapular -(- anterior circumflex.

Subscapular -|- anterior and posterior circumflex.

The Anterior Circumflex. — The* origin of this artery w'as relatively constant, conung from part III as a se])arate branch ill 22 cases and from a trunk common to it and the posterior circumflex in 21 cases. In the remaining 4 cases it took its origin from the subscajnilar in 2 cases, from a trunk common to it, the posterior circumflex and superior profunda in 1 case, and from the large trunk common to all the arteries in 1 case. Its distribution, as that given it under type I, was constant except in that case in which it was given off from the subscapular and supplied the area usually supplied by the humeral branch of the acromio-thoracic artery, that branch being small in this particular case. The cases in which the anterior circumflex is united with arteries ordinarily arising from the main artery may be grouped as follows:


.\nterior ami posterior circumflex, Subscapular ami anterior circumflex,

" " " aud posterior circumflex,


.'1 cases. 1 case. ] "


4. Truuk.


.5. Truul<.


( Auterior circumflex, "j

.j Posterior circumflex. V

( Superior profunda J

C Acromio-tlioracic. "1

I Long thoracic. [

I Subscapular. J I Anterior circumflex. |

(^ Posterior " J


The Posterior Circumflex. — This artery was ]ierhaps the most variable in origin of the axillary subdivisions being, however, constant in its distribution (see type I).

The places of origin are as follows:


1. From axillary artery.

„ ™ , f Anterior circumflex.

2. Truuk. < n i ■

\ Posterior "

3. Subscapular.


13 cases. 21 " !) "


I Posterior circumflex. \ Superior profunda. [" Acromio-tlioracic. I Long thoracic. i Subscapular. j Anterior circ-uinliex. [ Posterior " Brachial artery.


4. Truuk.


.5. Trunk.


J


The 3 trunks recorded in the table have been described elsewhere in this paper and are sufRciently clear from the table itself. The remaining muscular, cutaneous and intercostal branches are infrequent and may or may not occur. When present they are large or small as the case necessitates. The branch labelled " axillary fascia " is that which is usually described as the alar thoracic artery. It was present 8 times, its area being supplied by the larger subdivisions of the main arteries in their courses through the axilla.

The Posterior Scapular. — This artery arose from tlie axillary artery in 5 cases. The artery in its course turns backward, passes either between the trunks of the brachial jilexus or passes over them, courses along the superior margin of the scapula and then turns downward to pass parallel to the vertebral margin of the scapula. In its course it gives branches to the subscapularis, levator anguli scapuUv, trapezius, rhomboid major and rhomboid minor, supraspinatus and infraspinatus.

The suprascapular artery was found arising from the axillary artery in one ease. In one case the superior profunda was given oif in the axilla. In two cases not included in these records the axillary artery divided into the i-adial and ulnar in the axilla, and in these cases the anterior and posterior circumflex arteries and the superior profunda were given off by the radial.

The conclusions to be drawn from this study are:

(1) That while the origin of the subdivisions of the axillary artery varies, the distribution is practically constant.

(2) That type I, as here described, is the ordinary form in which the axillary artery is found.

(3) That the long thoracic artery and alar thoracic arteries are most frequently absent and that their areas of distrilmtion are supplied by the adjacent branches from the main artery.


TABLE SHOWINCx THE ORIGIN AND DISTRIBUTION OF THE BRANCHES OF THE AXILLARY ARTERY

IN FORTY-SEVEN CASES.



Origin.










D


STKIBUTION





















o


a5









(d
















ft)







u























p. n

"3

o

<y




p.




^ o


S3



o

DO





o c



a

cS

to

§





4-1

o


03





BRANCH.





03

n O


CO

o


00

s

m

o


OQ

3

00

o


s

00


o

a

a

03


a -a .2§


•a i

3



o

a o


S

a

be 03

s


'i ■§

to

9


S


a

3 'o


a

o





a o

W s- OS


•3

3

3

s

p.


O

p



— 3



S3



C3 PL,


a



a


ft>


.0


c3

o


S3 u o

o


2 a

° 2 u S


> J3


n



n

3 03



o

<o


.2


o}


c


i.



sterio scapu] perior


a s.


■d

"S


tn

OS



fU


to


C-l


CO


■*


lO


!U


p^


Ph


3 GO


3 OQ


o


0) 00


^



Pm


^.


<i


O


m


<


^ ^



a;


3


Superior thoracic


40




40


26


9


4


2






1



5















Acromio-thoracic


40


5



7 1 2


24 4 6


S4

n

22


6 11 33


2

5

41


41

1 1


38 8 8


45


4.S


3 5 43



2

11

41


1

3 41














Long thoracic


a


9







7










Subscapular


2


s


35




45


23


9


2






1


V







April-Mat-Junjs, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


143



Origin.


Distribution.


BRANrll.




OS


aj

V

a.

to

■3

CO

a

^ (a


(ft

C8 to


It

a>

a a


&



V

1— (


a


3J U 03

Pu

CO

"3

to



'5*

a

n

S

u a p4


a

a

■3



•a •11

a a

in

is ss

fl4



QD

o3GO


CO

03 03


s.

od


a


m

^

CO

3

a

m

IlU


'to


CO

a

'to

-5


a

[O


03

m

a

u

'u

■c

(0



a

3



.2 "0

CO

CO

fl

o3 >%


CO

2 3

u

03



g

C


to


It'

03

CJ

■5



a


■Jo

.2 9


0:

-3

d

3

2


03


t-.

a

a 1;


•3


3

CU 03

to


Auterior circumflex

Posterior circumtlex

Trunk common to anterior iiuJ posterior circumliex

Trunk common to circumflex arteries luul superior profiuulii



2


32 13

31 2



1

1


3 3

2



2


3


"2

9 .5


2


•3


3 31


•^


3 1



3


13

21

2

1


33

31

1

1

•■


8


1



9'


5


2 2



2



To subseai)ularis


15 1 3 3 5 1 1

1 1 1


.5 1

o

6 ..

1 ' ..

'2 "5

3 1 4

1 lil

1 1 19 1 ' 1

.. i ..



To pectoralis major

'I'o pectoi'alis minor



I'ectoral Ijraneli

To subclavius ami clavicle

To axillary fascia

Articular

1 st and 'Jnil interspaces

riiiil iuterspace



To coraco-brachialis .... . .


.... i 1

1 . . - ■ 1 . .


301 ..





  • 1 ■ ■


20






Posterior scapular


.5

1


I


Superior profunda



3







..





TYPE I, 20 CASES.


BRANCH.


Orioin.


Distribution.


■" ?



-5 1



E=



i-i4



ta '



rj



CO



tM


^


"


rt


a!


3



si

CO


03




« 


CO



C


^


Q


REM ARK. S.


1. Superior thoracic

2. Acromio-tboracic

3. Subscapular


4. Anterior circumflex .


5. Posterior circumflex ,


8.

9. 10. 11. 12. 13. 14. l.i.


Trunk common to anterior and posterior circumflex arteries.

To M. subscapularius

To pectoralis major

To pectoralis minor

Axillary irlands and fascia

Articular

2nd and 3rd interspaces

Coraco-bracliialis

Biceps

Posterioi- scapular


19


19


20


.51 lHil9


20


20


19


20


11


19


12


10


10


( In the absent case the region -1 was supplied by the acromio


upplied by thoracic artery.


8. times from a branch common to circumflex arteries (see line 6).

8 times from branch common to circumflex arteries, 4 times from subscapular, 1 case from brachial artery (see lines 3 aud (i).


144


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


TYPE II, 9 CASES.



Origin,


Distribution.



BRANCH.



03


Pu


V 03

P.

m

a

CO


03

P. CO

a

1— ( •a


CO

n

T3

u

CO


6

CA 1>


0)

o

03 n

a


tA

o

Ph


1-^

o

d

a

■3

P-i


s


-" ° .2

la p-i


CO

3 CO


1

9 ft

. o3

QQ

■« 03

OS _tO

1.1

" I'So

^1^


co'

3

a

a

CO


'co t •a

CO

3

a

CO

c3

a


03

g

£

CU


0)

a

3

E

v m


Ph


M

QJ

a

3 a

'0

.2

<


sa

to 03

<H

t3

a

OD

"bt, !>. 03

'm

<1


.2 a


1


CO

p.


o3

<



a


2 3

II

2-(


03 t3

3 3

"S

u P.

.2 'n

o<

3 00


3

§•


CO

eg

p.

3


REMARKS.



7 9


11



7 3

1


4 3 2


3 3 9


1

9 3


5 6


7 1

"s


6 6

'2


9


8


5 9


9


9 6


3

6


6


1


4

1


1

4 4


3

1


3'


3


■■



1


1


Absent twice, supplied by \ acromio and long thoracic


Acromio-thoraeic


(see lines 3 and 3).

Pectoral branch absent twice, , area supplied by long thoracic ' (line 3) and pectoral branch (line 11).

( Large in 3 cases, supplying J the subscapular area in part





9


( (see line 4). Small in cases, being confined to dorsal and scapular region





4 3

4

1

1

3


1




principally (see text).

For remaining place of origin see lines 4 and 7.

( For remaining places of origin j see lines 4, 7 and 8.

f For other origins of circumflex \ arteries, see lines 4, 5, 6 and 8.





7. Trunk, common to anterior and

posterior circumtiex arteries .

8 Trunk




9. Branch to M. siibscapularis


3

1 2


1

1

1



1 1 Pectoral lirauch



12 Articular











1










•;





TYPE III, 7 CASES.



6

7


7


4

1

3

>


1

]

1 1


6

3 1

2


.5

4 4

3


2

3 .5


2

7


2

7


7


6

a

1


7


7


7 2


7


7


7



3

1 3


4 3


2

1


3


3


3


1


1



( Absent once, supplied by ■1 acromio-thoraeic and sub

3. Acromio-thoraeic


( scapular.


4 Anterior circumtiex



For 3 remaining cases see line 6.


5. Posterior circumflex

6. Trunk, common to anterior and

Ijosterior circumflex

7. M. subscapiilaris

8 M coraco-bracbialis



1

] 1

1 1


J From subscapular in 3 cases. } From trunk (line 6) in 3 cases.

See lines 4 and .5.





10 Articular . .




11. 1st and 3ud interspaces

12. Br to deltoid


3



13 M pectoralis minor ...












1






April-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


145













TYPE


IV,


4 CASES.












Origin


Distribution.



■ BRANCH.


3H


rt ^



V

as P.

c

oa


75


o


a m

0)

a


cS

ZJ

a;

+-> a

xa


a

o


o a

a

rXi

O

0.



a

o

XK


03

u

V3 1/1


03

3 D. si

CO

33 cfi

O -O

o 'Sii

V


03

3

a

M

a

03


o ■a

CO

3

a

m '■H


o

a

CO

2


S

CJ

o .2

to

o Ph


a

t-.

j O

V

<


w T3

a

00

CI t^

<5


to

X2

6

o o


D.


03

3 o

«1


s.

03 CJ

en

a

o

0)

o

V

-«J m

O Ph


03 T3 3 3

CH O ^

P.

_o a

3


REMARKS.


1. Superior thoracic

8. Acromio-tlioracic


3


4


4

1 1

a

3

1 1


3

1


1

4


4 3


1

4


4


4


3


4


3


1 4

3


4


4


4


3


1

1 o

"*


1 1


1 1


3


s


"


• 1


1


j Absent once, supplied by acro( mio-thoracic (see line 2).


4 Anterior circumflex




j For 3 remaining cases, see lines





( 3 and 6.


6. Circumflex trunk





See lines 3 4 and 5



3


1



3



8. M. coraeo-brachialis

9. M. biceps


j No branch from axillary, supplied ( by brachial in 1 case. Same.




2





Represented by a definite branch twice (see line 3 for 1 case)


13. Posterior scapular


1



remainder supplied by various arteries. See text


13. Superior profunda


See text

















TYPE


V


, 3 CASES.











1. Superior thoracic


2


1

1 2



3

1


1

I 2


1 2


1 2


1 3


1

3


1 1 2


1 2


1 2


1 1 2


1 3


i'

2


1 2


3


1 3


1

9


1








3. .\cromio. thoracic



3. Subscapular




See lines 2 and 3.


5. Anterior circumflex

6. Posterior circumflex

7. Trunk, common to anterior

posterior circumflex


and


















TYPE


VI


,


2 CASKS.











1. Superior thoracic "


2 3 3



3

1 1

1

"i 1 1


2 '3


1 1 2

2


2

1


2 1

1


3


1

i


1

2


3


1 1


2


2



3 2

I ■

1


3



1 1


1 1


1

1



■■


• ■






i Pectoral branchabsent in onecase -j and small iu the other. Sup( plied by pectoral branch (line 8)

I Teres major supplied by dorsalis ^ scapular, getting no branches ( from subscapular direct.

See line 7 for remaining origin.

See line 7.

See lines r^ and 6. See line 2.


3. Long: thoracic

4. Subscapular


.5. Anterior circumflex




tJ. Posterior circumflex




7. Trunk, common to anterior aud posterior circumflex




8. Pectoral branch


2



9. Articular






11. Biceps






1



See line 2 for remaining case.














TYPE


VII,


2 CASES.












1 2 3



I 1

1


1

1

1


1 1


1

1


2 1


3


1


1

1

1 1


2


2



1


2


1 3


2


2


1 1


1

1


1

1





I


i


See lines 3 and 8. ("Pectoral branch absent iu 1 case (see line 8), supplied by pec

2. Acromio-thoracic



toral branch and by sub [ scapular (see line 3).


4. Circumflex trunk


For remaining case see line 5. See line 4.


.5. Trunk






1


7. Pectoralis minor



8. Pectoral branch



j See line 3. Supplies pectoral


9. Axillary glands aud fascia


I area of acromio-thoracic Was present as a rather large artery both in this case and in that from the subscapular (see line 3).


146


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


ON THE ORIGIN OF THE LYMPHATICS IN THE LIVER.


By Franklin P. Mall, Professor of Anatomy, Johns Hopkins University.


The ori<Tin of the lymphatics of the liver was first deiinitely determined hy MacGillavry," who studied this subject under the direction of Ludwig. Long before the work of Macrjillavry it had been observed that ligature of the bile duct was followed by passage of bile over into the lymphatics, and the artificial filling of the lymphatics naturally followed by injecting a colored fluid into the bile duct. Sections of liver, in which the lymiihatics had been filled with Prussian blue, or with as]ihaH, showed that the fluid injected into the bile ducts leaves them at the periphery of the lobule to enter spaces surrounding the blood capillaries, the so-called perivascular lymph spaces. These spaces communicate at the ]ieriphery of the lol)ule directly with the interlobular lymph channels. Frequeiitly there is an extrava.«ation of the injection mass into the blood capillaries of the lobule.

These observations were subsequently confirmed by numerous competent investigator.?, using the method employed by MacGillavry as well as that of direct injection of Prussian bhie into the walls of the portal and hepatic veins. In successful injections made in this way it is found that the Prussian blue injected enters the lobule to encircle its blood capillaries." Such injections, however, are always accompanied with numerous extravasations of the injected material into the tissues ])etween the lobules, and often there is a secondary injection into the blood cajiillaries of the lobule. This fact has raised an objection to the dii-ect injection of the lymphatics from the bile capillaries. It appears more probable, the opponents say, that the extravasation of bile, or the injected material into the interlobular spaces, enters the lymphatic radicals of the capsule of Glisson, and from them the larger lymph cliannels and the perivascular spaces of the capillaries are tilled. Furthermore the injected mass may pass from the pericapillary spaces directly into the capillaries, thus accounting for their frequent injection.

According to Fleischl,' all tlie bile is taken up by the lymphatics after ligature of the bile duct, and in case the thoracic duct is also ligated no bile or only a trace of bile ever reaches the blood. The observation of Fleischl has been confirmed by Kunkel,' Kufferath ° and Harley." It is extremely difficult to understand why the bile does not enter the blood capillaries in case it passes from the bile capillaries over into the perivascular spaces before it reaches the interlobidar spaces after ligature of the bile duct. A further objection to the idea that the perivascular spaces first take up the bile, after ligature of the duct, is the fact that fluids


1 MacGillavry, Wiener Sitzungsber., 1SG4. - Budge, Ludwig's Arbeiten, 187.5. 3 Fleischl, Ludwig's Arbeiten, 1874. ■> Kuukel, Ludwig's Arbeiten, 187.5. !• Kutlenitb, Arch, fur Pbysiol., 1880. "llarlcy, Arcliiv fiir Physiol., 1SH3.


injected into the bile duct pass with ease over into the lymphatics but only with difficulty into the bile capillaries. In all cases it appears as if the main origin of the lymphatics is at the periphery of the lobule and that the radicals communicate freely with the perivascular lymph spaces. Furthermore, it appears that the course the bile takes after ligature of the bile duet, or of a fluid injected into the bile duct in passing to the lymphatics, is between the lobules or at least at their extreme periphery. This idea is greatly strengthened since we know that the walls of the capillaries of the lobule are extremely porous, being composed of a dense layer of reticulum fibrils ' upon which lie the endothelial or Kupfl'er's cells. This layer of reticulum fibrils encircling each capillary has been described from time to time by many investigators, and has been isolated by Oppel ° and by myself.' Oppel obtained clear pictures of the connective tissue of the liver lobule by means of silver ])recipitatioii, while I employed Kiihne's method of pancreatic digestion to remove the cells, followed by some intense stain like acid fuchsin. The nature of theso fibrils is still under discussion but that matters little for the present communication. It is sufficient to know that flic fibrils of reticulum form a basket-like membrane surrounding each capillary of the whole lobule, the interior of which is only partly lined by Kupffer's syncytial endothelial cells. The capillary walls then are very pervious, blood plasma passing easily from them out into the perivascular spaces to bathe the liver cells.

It is well known that a large quantity of lymph is constantly passing from the liver, much more than from any other organ. That this lymph comes directly from the blood is indicated by its high per cent of proteid matter, nearly that of the blood, and from two to three times that of the lymph from other parts of the body.

The course the lymph takes from the blood to the lymph radicals, i. e. its natural course, can easily be marked by injecting colored gelatin into any of the blood-vessels. 1 have usually found it most convenient to inject the gelatin into the portal vein, but it is just as easy to fill the lymphatics by injecting either the hepatic artery or hejiatic vein. In all cases the colored fluid reaches the main lymph channels in the same way. The colored gelatin flows with great ease from the capillaries at the periphery of the lobule as well as from those around the sublobular vein into the lymphatics. After the lymphatics have all been filled it is well to inject a small quantity of fluid of different color into the bloodvessels. A much better method of making double injections is to mix red granules with a blue gelatin or blue granules


1 Kupffer, Arch. f. Mik. Anat., ^4.

•* Oppel, Arch. Anz., 1890.

'Mall, Abhaudl. d. K. S. Ges. d. Wiss., .xvii, 1891,


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


147


with a red gelatin, the fenestrated lining membrane of the capillary acting is a sieve which allows the fluid to pass but holds back the granules, as is the case with the blood wheu normal circulation is taking place.

If the portal vein is injected with Prussian-blue gelatin under a low pressure, it is found that in a few minutes the lymphatics are all filled with the blue mass. Jjivers injected in this way are best hardened in formalin and then cut by tJU' freezing method, for alcohol causes the gelatin to shrink. Such sections show that the blue fluid has entered the lym|)haties at the periphery of the lobule. More instructive arc the specimens when the injection is stopped just as the first lymjihatics are filled with the colored gelatin. By following the larger lymphatics back into the liver substance it is found that the interlobular connective tissue is entirely filled with blue where the lymjihatics are injected, but only partly colored blue when they are not. In other words, the blue extra ■-■ - • /©./ L



Fig. 1. — Section throuj^h tlie periphery of the liver lobule of a cat. The hepatic artery was iujecteii with cinnabar gelatin, ami the portal vein with Prussian-blue gelatin, stained with Van Gieson's stain, x .500 L, lobule of liver ; <■, oapillarios ; a, artery; ?, lymph vessel; pi'l, times, perivascular lymph space ; pW, perilobular lymph space; w, bundles of fibrils of white tlbrous tissue.

vasates from the jieriphery of the lobule, invades the connective tissue until it reaches the beginning of the lymphatics, when of course it is carried rapidly from the liver. The nearest course from the lobules to the lymphatics is between the lobule where the amount of connective tissue is small, so when colored fluid is beginning to enter lymph channels the tips of the capsule of Glisson are entirely colored, while larger portal spaces are encircled by a zone of the color. Furtliermore it is found that in certain instances when the injection was not continued long enougii tlie libu^ did not enter the lymphatics. In such specimens it is found that all the interlobular spaces are surrounded by a zone of colored gelatin which does not enter the main lymjih channels.

A successful injection of the lymphatics is illustrated in the accompanying figure. The section was stained with Van Gieson's stain which gives a very satisfactory result. The granular blue enters the capillaries of the lobule, c, with ease.


and from them the liquid blue is filtered through the capillary walls to enter the perivascular lymph space. This space communicates at the periphery of the lobule directly with a large lymph space between the liver cells and the capsule ot Glisson, which I shall term the perilobular lymph space. These spaces in turn communicate with the lymph radicals.

Injection of the blood-vessels of tlie liver with aqueous Prussian blue fills the capillaries only, and in all cases it is shown that there are no capillaries between the periphery of the lobule and the interlobular connective tissue. The liver cells come directly against the capside of Glisson. An injection of brief duration with blue gelatin soon fills the perilobular lym])h spaces, so that it appears as if all groups of liver cells at the periphery of the lobule were separated from the interlobular connective tissue with capillaries. In ease cinnabar granules are mixed with the blue a few of these granules are found in the perivascular and perilobular lymph spaces. The openings in the walls of the capillaries are large enoiigh to allow a few of the smaller granules to pass through. As the injection is continued the blue invades the connective tissue spaces from the lymphatic radicals more and more until a lymph channel is reached, when of course it flows rapidly from the liver. -Were there a direct channel from the perilobular lymph spaces the blue should flow through it at once without further filtration through the interlobular connective tissue spaces. The course the cinnabar granules take also speaks against a direct channel between the perilobular lymph spaces and the interlobular lymph channels. A few of the granules enter the ]ierilolnilar lymph sjiaces, but none of them reach the main lymph channels. All of my specimens without exception force me to the conclusion that there are no direct channels connecting the perivascular and perilobular lymph spaces with the lymphatics proper other than the ordinary spaces between the connective-tissue fibrils of the capsule of Glisson. These spaces, however, are relatively large, permitting of a rapid diffusion through them.

Interstitial injections into the walls of the interlobular veins natui-ally liU the surrounding lymphatic vessels, and when no valves are in the way the injected fluid passes to the origin of the vessels, or lacunte, which are only in part lined with endothelial cells. From here the fluid passes through the main connective-tissue spaces to the periphery of the lobule into the perilobular and perivascular lymph spaces, and frequently from thtm into the blood capillaries. When the injection is made through the bile ducts I have always found that there is an extravasation of the fluid from these at the periphery of tlie lobule which immediately enters the lymph radicals, although the bile capillaries are often injected well into the lobule. The extravasation docs not take place from the bile capillaries, only from the duct as it communicates _with the capillaries; also it does not take place from the larger bile ducts. Such extravasations naturally are picked up by the lymphatics and are at once carried from the liver. If after ligature of the bile duct the bile enters the perivascular lymph space within the lobule it may still be carried to the


148


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 131-122-123.


lymphatics, as the direction of the current of lymph is constantly from the blood capillaries to the lymphatics.

It is well known that the liver cells arise from the enibiyonic bile dncts. and that in the further growth of the liver the bile ducts must elongate in order to adjust themselves with the growing liver. Hendrickson '° has shown by staining the bile capillaries and ducts of tlie embryo's liver by Golgi"s method that the tip of the primitive l)ile duct is added to by a coalescence of the bile capillaries at the periphery of the embryonic liver lobule. My own observation on the liver lobule after it is well formed is that whenever karyokinetic cell figures are present they are at the periphery of the liver lobule, i. e. at the junction of the bile capillary with the bile duct. It also appears that the vascular walls of the embryo are much more pervious than those of the adult. Judging by the ease extravasation takes place when the blood-vessels of embryos are injected. This observation taken with that ol the growth of the bile ducts may be an explanation why the e.xtravasation of a fluid injected into the bile duct takes place at the periphery of the lol)ule. A further hint in this direction is the observation that it is easy to inject the lymphatics from the blood-vessels of an inflamed area. I have often seen the lymphatics of an inflamed intestine filled with blood, and upon injecting the blood-vessels found that the fluid readily entered the lymphatics."


'"Hendrickson, Johns Hopkins Hospital Bulletin, 1898. " See also Sigmund Mayer, Anat. Anz., 1.S99.


That the capillaries of the liver communicate more freely with the lymphatics than do the bile ducts is jiroved by injecting the bile duct and the portal vein with fluids of different color under the same pressure at the same time. In all the experiments I made the fluid injected into the vein appeared in the lymphatics first. In many instances beautiful injections of the lymphatics were obtained from the vein while the fluid injected into the bile duct did not extravasate at all, showing at least that the veins communicate with the lymphatics much more freely than do the bile duets.

The conclusions to be drawn from the above observations are (1) that the lymphatics of the liver arise from the perilobular lymph spaces and that these communicate directly with the perivasculai" lymph spaces; and (2) that the lymph reaches these spaces by a process of filtration through openings which are normally present in the ca|)illary walls of the liver. Fiirthermore, the fluid injected into the lymphatics from the bile duct leaves the duct as it enters tlie lobule and is at once taken up by the lymph radicals and perilobular lymph spaces, and from tliem extends, as a secondary injection, to the perivascular lymph spaces, and often into the blood capillaries of the lobule. The larger lymphatics accompanying the portal vein arise between the lobules near their bases, while those accompanying the hepatic vein do not arise within the lobule but around the larger sublobular veins.


BORN'S METHOD OF RECONSTRUCTION BY MEANS OF WAX PLATES AS USED IN THE ANATOMICAL LABORATORY OF THE JOHNS HOPKINS UNIVERSITY.

By Chahles Eussell Bakdeen, Associate in Anatomy, Johns Hopkins University.


The wax-plate method of reconstruction (Plattenmodellen methode) described by Born in 1876 ' has proved of great value in the study of the morphology of embryos. The method has received its most extensive application in the hands of Born, of His and of various pupils of these investigators. In general, however, it may be said, that the value of this method as an aid to the microscopic study of form has not been sufficiently appreciated.

In part this lack of a more general application of the method has been due to certain technical difficulties which tend to make it cumbersome and time-consuming. Yet by no other method can so accurate an idea be obtained of the form of those structures which from their minuteness or complexity of relation cannot well be dissected out.

Considerable application of the method has recently been made by different persons in this institution and each worker has contributed something towards making the method more effective.


I Morph. Jahrb. II; Arch. f. mikr. Anat., xxii, p. 584.


As originally described by Born several steps are essential for the successful application of his method. These may be tabulated as follows:

A. Preliminary steps.

1. Obtaining a good picture of the embryo or object to be reconstructed.

2. Hardening, staining and sectioning the object.

3. Drawing magnified enlargements of the sections or such parts of them as it is desired to reconstruct.

4. Preparation of the wax plates.

5. Transference of the image to the surface of the wax and cutting out the wax plates.

B. Constructing the model.

1. Piling the wax plates.

2. Removing parts not essential to the reconstruction desired and rounding oft' of the parts reconstructed.

3. Strengthening and finishing the model.

I shall consider these steps in the order named.

A. Preliminary steps.

1. Before proceeding to section the object to be recon


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


Ui)


structed it is important to obtain good pictures of its external form. With such a picture at hand it is much easier to pile up the wax plates which represent the sections through the object. This is especially true when the object is symmetrical, as in the reconstruction of embryos, profile views of which are invaluable in this work. If the picture be enlarged to the magnification of the model desired a valuable control is furnished. A series of parallel lines may then be drawn through the picture to represent the planes through which the knife has passed in sectioning the embryo, so that the position of every plate is indicated.

For general purposes photography is undoubtedly the most convenient method of recording the gross external features of the object. If the object be very small as, for instance, an early human embryo, the camera may be so placed that the image in the negative is enlarged from two to four diameters. It is found that the most convenient way of photographing embryos is to place the camera wdth the axis in a vertical direction and the lens pointing downwards. A stand for holding the camera in this position and raising or lowering it is easily constructed. Ordinary lead shot seems to be especially good for holding many small objects in the position in which it is desired to photograph them.

For detail in the distant as well as the proximal part oi the object it is a great aid to make use of a stand capable of being raised without moving the object laterally. In this way, if the diaphragm be closed down so as to make the exposure a long one, the object may from time to time be brought slightly nearer to the lens of the camera, so that parts more distant are brought into sharp focus.

From the photographic plates thus obtained lantern slides are made or the negative itself is used to project the imag. at the required magnification upon a screen. Free-hand drawings are then traced on a paper upon which the image falls, or, if desired, bromide enlargements can be made. In this way accurate records can quickly be made of the external appearance of the object to be studied, yet no special talent for drawing is required. In the study of embryos the jirofile view is the most essential one, though others also prove of great value.

2. The only real essentials in the technique of obtaining serial sections of the object to be studied are that the series should be complete, the sections perfect and of uniform thickness. As pointed out by Born, the most convenient sections for this work are those from 20-40 microns in thickness. For sections of this thickness we have found alum cochineal to give uniformly the most satisfactory stain. It is important to know which side of the sections was uppermost during the cutting, so that in the subsequent reconstruction a true and not a mirror image of the object will be formed. For this reason it is well to make it a uniform practice to begin at the head when cutting transverse sections through an embryo, at the right side when cutting longitudinal vertical sections, and at the dorsal side wlien cutting liorizontal sections and to label the sections in the order in which they have been cut.


3. For making drawings of the sections we have found that in general a projection apparatus is more convenient than a camera lucida unless the sections are small. Our projection ajijiaratus is set up in a large dark room.

The illumination is received from an arc electric light or from a heliostat. An ordinary microscopic stand with the tube in a horizontal direction is used when the sections are small and a high magnification is desired. Eye piece and draw tube are usually removed and the objective is used as the magnifying lens. In case of larger sections a projection lens similar to that used for lantern slides is utilized.

The image is projected upon a screen which runs on a track. The screen can be moved toward or away from the microscope by means of windlass situated near by. In this way any desired magnification can be quickly obtained by using an appropriate lens and bringing the screen into the proper position.

The screen which I devised for our dark room has attached a leaf which can be lowered so as to form a drawing table and a mirror that can be placed at an angle of 45° over the table. In this way the image is projected on a horizontal surface so that tracing it is easier than when it is upon a vertical surface. In using an ordinary mirror a double image is projected but that from the surface of the mercury is so much brighter than that from the surface of the glass that no difficulty is experienced in drawing accurate outlines.

Fig. 1 illustrates the apparatus here in use.



Fig. 1. — At the right the projection screen is shown in position on the tracli. The mirror is lowered to an angle of 45° and the drawing table is extended horizontally below this. At the left are shown the windlass used for moving the projection screen and the shelf used for holding the projection lantern.

In drawing pictures of the sections a careful outHuo of those main features which it is desired to bring out in tlu' reconstruction is the great essential. In addition it is often of value to distinguish by using pencils of various colors the different organs in structures as they appear in the section.

If desired, direct bromide enlargements can be made of the sections on the slides. This is the method preferred liy His. The simpler method described above we have found, liowever, to be more convenient for general purposes.

The outline drawings may often be elaborated to any desired extent when the sections are subjected to carefvd microscopic study. It is a great help for the subsequent reconstruction to label, so far as possible, the various structures in the outlines of the sections before proceeding to the wax plates.


150


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 131-122-123.


4. Much trouble in the preparation of the wax plates is to be saved by using plates of a uniform thickness and by making the magnification of the object under reconstruction correspond. The most convenient thickness for general use is 2 mm. Occasionally, for coarser work, 4 mm. plates have proved of value. It is very easy, with the apparatus above described, to make the ratio of the dianftter of magnification of the drawings to the diameter of the sections equal to that of two millimetres to the thickness of the section. If plates 2 mm. thick be used and every section be drawn, sections 20 mm. thick = 1/50 mm. must be magnified one hundred times. Or if desired, as is more often the case, every other section may be drawn at a magnification of fifty diameters.

For making the wax plates we have a large zinc pan with vertical sides. Its surface area is such that one kilogram of the wax mixture which we use will make a plate 1 mm. thick. The method of casting the plates is essentially that described by Born. Boiling water is run into the pan to the deptli of several inches. On the surface of this the hot melted wax mixture is poured and quickly forms an even, smooth, layer. Bubbles, which occasionally appear in the wax, may be quickly exploded by turning the flame of a Bunsen burner on the surface of the wax where they appear. As the wax plate cools it is necessary to free it from the sides of the pan by running a knife along the edge. Before the plates are perfectly cool they may readily be cut into smaller plates of any desired size.

The wax mixture in use here is composed of 950 parts of bees-wax and 50 parts of white rosin. Often, especially in summer, paraffin is added to give additional toughness. Black plates are made by adding lamp black to the melted wax, until after thorough stirring the mixture has become uniforndy black. The amount by weight of wax necessary for a plate of a given size is obtained more easily by experimental trial than by calculation. A certain amount of wax becomes attached to the sides of the pan by surface tension, so that slightly more wax must be used than the amount one is likely to determine by calculation from the specific gravity of the wax and the size of the ])an. On the other hand if a pan of a given size be used the amount of a given wax mixture necessary for making a plate of given thickness may be determined by a few trial castings.

The outlines are transferred to wax by means of red or blue tracing paper. The wax plates are then placed upon glass and are cut with a small, narrow knife and in a warm room.

B. Constructing the model.

1. The janitor can be trusted to trace the outline drawings on wax, to cut througli the wax with a sharp knife where the outlines are traced and to make the preliminary piling. Usually two preliminary piles are made, one of that part of the wax plates which represent the sections and one of the wax plates themselves after removal of the parts representing the sections. From the former a positive, from the latter a hollow negative image of the original object is ob


tained. In this piling an enlarged picture of the object is of very great help. As originally suggested by Born, in case of symmetrical objects a surface outline may be drawn on card board and cut out, thus giving a fixed ridge against which to pile the plates. If but one side of any embryo is to be reconstructed from transverse sections it is of great help to cut each plate off sharply at the midline and to pile the plates against a profile outline of the embryo situated on a Ijoard which has been placed ]ierpendicular to the plane in which the plates are piled. In case the reconstruction of some internal organ is wanted it is usually of advantage to reconstruct at the same time the external form of the object, so that when the jjlates are piled the iiuage they form may be compared with the picture of the original object. After getting the plates composing the positive image of the object into proper position, it is easy to trace two or three of its surface curves on paper or to represent them in wire and then to get the negative formed, as described above, into true shape. Plaster casts can then be made in this negative mould. The plaster casts, representing the external features of the original object, are very valuable to have at hand, while engaged in reconstructing the internal features from the wax plates.°

The method of making every fifth ]ilate a black one ha-^ proved to be extremely valuable in arranging the wax jilates. In this way it is easy at any time during the reconstruction of the model to count up and place any given section.

The method of reconstruction which I have found most convenient is as follows: After the "plates are placed in proper jiosition so that the external features of the object are accurately portrayed, I begin by taking oil' five plates from one side. The draAvings of the sections I likewise have pinned together in groups of five in the same order in which the plates are piled. By going over the five finished drawings it is easy to obtain a good conception of the form of the structures represented in the block of five plates under ctmsideration. I have at hand a paper of fine pins and these 1 l)ress down through the various structures seen in section on the surface plate, and in such a direction that they will pass into the same structure in the sections below. When the parts of the plates which represent the structures to l)u reconstructed are thus firmly united by pins I remove the intervening portions of the wax plate with a pair of force] s. Thus, in a very short time, one is enabled to l)ring to light the form of the structures lying within the block of five sections. The pins hold the various bits of wax firmly in place and serve to strengthen the model in every way. When I feel satisfied with the appearance of the structures in the first block of five sections I proceed to the next and treat it in the same way. Those structures which are cut in both liloeks of sections may at the same time be ])inned together. After two or three blocks of sections have thus been piled up it is often well before adding another lilock of five sec


■J Many methods liave been devised of pilini; plates acciirdhiir to special marks. The method devised by Wilson, Zeitschrift fiir wissenshaftliche Miliroscopie, xvii, IDOO, page 17T, seems a good one.


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tions to fuse them together with a hot knife and thoroughly to strengthen the reconstruction so far as it is completed. For strengthening piles of narrow strips of wax, representing sections through membranes and the like, a wire netting is of the greatest value. Perhaps the best form of wire netting for general purposes is a copper netting with 10 strands to the centimetre. The copper netting has no tendency to cause subsequent warping, as is the case with iron netting. The netting is heated in the flame of a Bunsen burner and is then applied to the surface which it is desired to strengthen. In case of narrow columns, such, for instance, as are formed in the reconstruction of blood-vessels and nerves, copper wire is of the greatest value. This can be heated and sunk in at one side and then fused over.

After the model is once well started the subsequent building up can proceed with great rapidity. Plates in blocks of five are added as described above until the model is finished. Of course a greater or less number of plates than five may be used to a block. In most of my work, however, I have found blocks of five, with a black plate on the surface of each block, to give the most satisfactory results.

In order to keep the various structures distinct during the reconstruction it is often of value to paint them with dilferent colors, while the work proceeds. The various structures of a model built up as described may be removed as completed, or during the course of reconstruction, and then readily replaced. Pins are of great value in holding structures iri


place and for indicating where a structure removed must be replaced in order to regain its proper position.

If it is desired at any time to cut the model in a given direction the pins which hold the pieces of wax together may be readily cut with scissors.

3. I have mentioned methods by which ihe model is greatly strengthened during the course of reconstruction, the use of ])ins, of wire netting and of wire. All three means may be employed thoroughly to strengthen the mod«l after the first rough reconstruction. The wire screening is then especially valuable. Of course it is possible to add free hand and with a good deal of accuracy structures which from their delicacy are diflicidt to model. This is true of blood-vessels, nerves and of fine membranes. The blood-vessels and nerves may be readily constructed by covering copper wire with wa.x, the membranes by covering a netting of narrow meshes with a thin coating of wax.

In rounding and smoothing up various structures in a model so as to give it a finished appearance, semi-melted wax a])])lied with the fingers or with a spatula is of the greatest help.

Tlie model is greatly protected in many ways by a thick coating of paint. Hot weather seems to have a far less detrimental effect on such models than on models unpainted.

We have found jihotograjdiy of great help not only in recoi'ding the condition of the finished model but also, at times, during the course of a reconstruction.


MODEL OF THE NUCLEUS DENTATUS OF THE CEREBELLUM AND LPS ACCESSORY NUCLEL

By Harry A. Fowler.

(From tJu Aniilomictrl Lahoyaionj of the Johns Hopkins University.)


At the suggestion of Dr. Barker I have undertaken the study of the central gray matter of the cerebellum and its relations to the white fibre bundles to which it is intinuitely related. It has seemed advisable to make a partial report including a reconstruction in wax of the nucleus dentatus and its accessory nuclei.

In a study of the internal structure of the cerebellum it is necessary to consider the work of Stilling on this region. To him belongs the credit of being the firet to study the internal anatomy of the cerebellum by means of serial sections made in various planes and stained with dyes to bring into greater contrast the white matter and the gray masses. With the crude methods at his disposal for preparing serial sections and staining them, the drawings of Stilling show with remarkable accuracy the relations of these central nuclei to the white substance in which they lie buried and to which they are closely related.

The Material. — The model was made from a series of transverse sections through the medulla and cerebellum of a newborn babe prepared by Dr. John Hewetson in the Anatomical Laboratory of the University of Leipzig. The material was hardened in iliiller's fluid, cut ^0/'. thick, and stained bv the


Weigert-Pal method. Every other section was used and hence each section represents a thickness of 110 microns. A series of sagittal sections through the medulla and cerebellum of a new-born babe was also prepared and treated in a similar way for use as a control in measurements and to furnish an outline of the floor of the fourth ventricle. This outline was used in building up the model.

The Method. — Bern's method for nuiking wax jilates as carried out in this laboratory has been fully described by Dr. Florence R. Sabin.' A magnification of twenty diameters was decided upon, because (1) it gives a plate of convenient size to work with so that the numerous foldings of the surface of the dentate nucleus can be distinctly outlined, and (2) the thickness of the jjlates — 2.8 mm. — makes them easy to cut and convenient to liandle — two points of considerable practical value. Outline drawings were nuide first with a projection apparatus at a magnification of twenty diameters. These drawings were then controlled with a higher magnification before transferring them to wax plates.

In building the model a real difficulty presented itself — the


' Sabin, Contributious to the Science of Medicine, and .Jolins Hopkins Hosi)ital Reports, ix.


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[Nos. 131-122-133.


difficulty of controlling the curves. Inasmuch as the central nuclei of the cerebellum lie deeply buried in the wliite matter of the hemispheres and worm one does not have tlie assistance afforded by external form in building up the model. In studying the sections it was noted that the dentate nucleus and accessory nuclei are bisymmetrieal, and a prolongation of the raphe of the medulla dorsalwards Ijisccted the cereIjellum, passing through the middle point in the roof of the fourth ventricle. Corresponding points in the nuclei of the two hemisjiheres were equidistant from the median line so drawn and from the middle point in the floor of the fourth ventricle. In building the model these two guides were used: (1) the median line which controlled the lateral curve, and


to the lowermost (distal) section, in which the dentate nucleus appeared, was placed at a proper distance from the median line, i. e. the edge of the board and the upriglit outline of the floor of the fourtJi, ventricle, and fi.xed in place. The succeeding plates were piled with reference to these two guides and the plates already piled, and each plate as it was put in proper position was fused with the plates already fixed.

The outline of the nucleus dentatus is very definite and easily traced. Tlie capsule or Vleiss (Stilling) on the outside and tlie cor.' or llarkkern on the inside are both medullatcd and take the stain, thus distinctly limiting the yellow mass of cells composing the nucleus. The drawings could be very accurately made. In attempting to outline the accessory



TiXU &.ii\ N\[ai. Nuoa.m.

Fig. 1. — Transverse section of medulla and cerebellum (after Sabin, J. H. H. B., No. 81, December, 1897, Fig. 3.) Section at level of uucleus of glossopliaryngeus and vagus nerves. Section also passes througli upper part of the dentate nucleus and accessory nuclei. Long axis of nucleus is seen to form an acute augle, with the median Hue (formed by extension dorsally of the raphe bisecting the 4th ventricle aud the cerebellum), with the augle openiug toward the medulla. Dorsolateral surface of dentate nucleus is parallel to the surface of cerebellum. Corpus restiforme is seen to cover this surface. The accessory uuclei appear separated and broken up by the white meduUated fibres. Variatious in thickness aud foldings of walls of the dentate uucleus also well shown. Ililus ojiens medial- and ventralwards.


(2) the outline of the floor of the fourth ventricle which controlled the dorsoventral curve. In the sagittal series the section passing through this central point in the floor of the fourth ventricle was selected and an outline of the longitudinal curve of the floor was made. A flat surface having one straight edge was then obtained. This edge corresponded to the median line. To this edge was attached .the outline of the floor of the fourth ventricle, already described, at the proper angle corresponding to the angle at which the sections were cut. With these two guides fixed the plate corresponding


nuclei, however, one meets with a real difficulty. This applies particularly to the nucleus globosus and the nucleus of the roof. The nucleus globosus instead of forming one mass of gray matter is made up of several irregular groups of cells separated by deeply stained meduUated fibres belonging to the fibre systems of this region. These separate groups arc clearly limited with a magnification of twenty diameters, but when studied under higher powers one finds cells evidently belonging to these groups scattered among the dense network of deeply stained fibres. In studying the nucleus globosus


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153


through several consecutive sections under high jjowers one gets the impression tiiat the separate groups seen with a magnification of twenty diameters really form one nucleus; that this lai'ge mass of cells is separated into groups by the white fibres plunging directly through the nucleus; and this impression is further strengthened by noting the cells scattered among the fibres, included as it were by the bands of white fibres.

In outlining the nucleus of the roof one meets \\itli the same difficulty. In going over these two nuclei with a high power to correct the drawings for transference to wax I had to include the scattered cells referred to. I did this by making the nuclei solid, not attempting to indicate the space occupied by the fibres.

One other point is to be noted. The so-called accessory nuclei, i. e. N. emboliformis, N. globosus and nucleus of the roof, are usually described and figiired as entirely separate and distinct cell-mass. In this series of sections of the newborn babe, with the exception of the N. emboliformis, it has been difficult, indeed impossible, at certain levels, to separate these nuclei. The N. emboliformis forms a perfectly definite cell-group, in the lower (distal) sections, appearing as a thin, tongue-like ribbon of cells almost entirely occluding the liilus of the corpus dentatum. Sections at the level of the middle of the nucleus show it changing its shape, suddenly becoming thicker and shorter, but clearly separated from the corpus dentatum on one side and the nucleus globosus on the other side by thin, deeply stained bands of white fibres. The nucleus globosus also appears as a definitely limited and separate group of cells in the lower (distal) sections, appearing in sections a little above the beginning of the hilus of the corpus dentatum as a small oval area of gray matter. At a higher (proximal) level this oval mass is divided, as already indicated. At the highest levels it is not to be separated from the nucleus of the roof.

Corpus Dentatum. — It is embedded in the cerebellar hemisphere "like a peach stone" (Stilling). The distal end lies more deeply buried in the white substance; the proximal end approaches closely to the roof of the fourth ventricle, from which it is separated by a thin ribbon of white siibstance. Horizontal sections of the nucleus, as pointed out by Obersteiner, do not show the greatest diameter of the nucleus. This appears in sagittal sections.

The dimensions of the model of dentate nucleus are as follows:

1. Proximo-distal (sagittal), ID.Scin.

3. Mesolateral, (iu axis of nucleus ami nut at riglit angles to median line), 19.4 cm.

.3. Dorsolateral, (perpendicular to mesolateral axis), 7.8 cm.

Remembering that the longest mesolateral diameter forms an acute angle with the median line with the angle opening ventralwards one will understand the measurements given.

The nucleus dentatus is really a hollow shell or sac with its long axis directed antero-posteriorly (proximo-distally). This shell is flattened dorsoventrally or at right angles to its mesolateral diameter. The walls, which vary in thickness


from 0.3 to 0.5 mm., are thrown into numerous folds also varying in number and size in different parts of the nucleus. The folding of the walls gives to the svirface an appearance not unlike the surface of the cerebral hemispheres or to the gyri and sulci of the inferior olive. The shell of gray matter is not closed but freely opens above (proximally), while the ventral and mesial walls are incomplete in the anterior (proximal) two-thirds of the nucleus. This opening in the walls forming the so-called hilus — hilus corporis dentati — looks median-, ventral- and cerebralwards. In the distal one-third of the nucleus the walls are complete and in transverse sections appear as oval closed rings or ring of gray matter.

The hilus in the more distal sections opens directly medianwards; in sections at a higher level (cerebralwards) the opening increases rapidly in size, the ventral wall becoming less complete, while the dorsal wall forms a complete covering. As a result of this progressive shortening of the ventromesial wall the hilus comes to open wider and wider ventralwards. This direction is further emphasized by the relation of the nucleus emboliformis. In the most distal sections lying within the mouth of the hilus it is in very close relation with the dorsolateral border, indeed in the distal sections it may be considered as a continuation of the dorsolateral surface on to the mesial surface, being separated by a very thin band of white fibres. This relation continues throughout the entire length of the nucleus, there being only a thin space of separation through which pass the most dorsal fibres escaping from the Markkern of the nucleus dentatus.

In addition, the dentate nucleus presents for description two surfaces, (1) dorsolateral, and (3) ventromesial; and four borders, (1) mesial, (2) lateral, (3) proximal, and (4) distal.

Dorsolateral Surface, — This is the largest surface of the nucleus (Fig. 2). It is irregularly quadrilateral in shape and lies parallel to the surface of the cerebellar hemisphere. The lateral and antero-posterior (proximo-distal) curves are slight, the surface being quite flat. In this connection it is interesting to note that a portion of the corpus restiforme lies over this surface of the nucleus, forming a shell enclosing the dorsolateral surface. This surface terminates mesially by a sharp thin border in its upper (proximal) two-thirds, by a rounded mesial border in its lower (distal) one-third. Laterally it is limited by the thicker, irregular and rounded lateral" border. The proximal border also thin forms with the median line an obtuse angle opening spinalwards. The distal border is parallel to the proximal, is thick, rounded and is broken into by deep sulci. By reference to Fig. 2 it will be seen that the lowest sections of the nucleus includes only the mesial- portion of this border.

The dorsolateral surface is traversed by five parallel deep fissures, which run parallel to the long axis of the nucleus. Beginning with median line these may be designated as A, B, C, D and E. These fissures divide the surface into six columns or gyri. Besides these five primary fissures there are five secondary sulci, which are shallower and incompletely divide the primary columns or gyri into secondary gyri. By reference to Fig. 2 the following jioints will be noted: Fissure


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[Nos. 131-122-133.


A is parallel to the mesial border, it is relatively deep and its corresponding gyrus on the inner surface of the nnelens looks lateralward (Fig. 3). The proximal end of fissure A curves laterall)'. Fissures B and C present three curves, the pro.ximal and distal with convexities pointing mesially, the middle vi'ith convexity laterally. Fissure C is incomplete, its proximal end not reaching the proximal border. Fissures D and E form acute angles with fissure C with their proximal ends pointing obliquely medialwards. It will also be noted that the distal extremities of the columns or gyri are larger, thicker and divided by extension on to this surface of the fissures from the ventromesial surface. The deep fissures of the ventromesial surface alternate with the fissures on the dorsolateral surface. An exce])tion to this is in fissure D, which is really an extension on to the dorsolateral surface of the lateral fissure of the ventromesial surface. There is no evidence of distinct lol)ulation visible on this surface.

The secondary sulci are limited chiefly to the three gyri nearest the median line. In other words, the folding of the dorsal wall of the nucleus is greatest nearer the mesial and proximal borders; it is thickest nearer tlie lateral and distal borders.

Ventrolateral Surface. — This surface is incomplete in its upper two-thirds. It difi'ers markedly from the dorsolateral surface. It presents two deep fissures radiating from a point near the hilus about the level of the middle point of the nucleus. These fissures may be designated as (1) internal and (2) lateral. AVithin the internal fissure and nearly covered over by its projecting edges is a gyrus, broad at its base (distal end) and tapering above, becoming lost in the most proximal part- of the fissure. This gyrus, partly concealed within the internal fissure, divides thi^ fissure into two, both of which extend so as to appear on the dorsolateral surface. These two fissures, internal and lateral, of the ventromesial surface, divide this surface into three lobes, (1) internal, (3) median, and (3) lateral. The internal is the smallest and continues below the hilus on to the mesial border, being distinctly marked off from this border by a shallow s\ilcus. This lobe is broad at its proximal end, tapering off distally. The median lobe, broad at its base — distal end — narrows toward the point of divergence of the two fissures, internal and lateral. The internal and median lobes form the most distal part of the nucleus as viewed from its ventral aspect. They slope with a considerable curve to meet the almost perpendicular dorsolateral surface. They present no secondary sulci.

The lateral lobe is the largest. It forms the lateral border and extends on to both dorsolateral and ventromesial surfaces. On the former it lies lateral to fissure L\ while on the latter it is limited mesially by the lateral fissure. This lobe is most irregular in outline, is broken up by numerous depressions and several secondary sulci. One of these sulci, more conspicuous than the others, runs parallel to the upper two-thirds of the lateral border.

The upper two-thirds of the ventromesial border is incomplete; the margin is very irregular as will Ijost be understood


by reference to Fig. 3. In general, it may be said that this surface, as compared with the dorsolateral, presents (1) deeper fissures, which give the appearance of lobulation, (3) thicker walls, and (3) fewer foldings of the walls.

The proximal end of the nucleus being open this border is limited to the thin edge of the dorsolateral surface, and the very small part of the ventromesial surface. This border slants obliquely spinal- and medianwards. The other borders have been referred to in describing the surfaces and the hilus.

llie Accessory Nuclei. — The form and outline of the accessory nuclei, i. e. the nucleus emboliformis, nucleus globosus and nucleus of the roof, have been already referred to. Figs. 5, and 7 show these nuclei in relation to the dentate nucleus. In Figs. V, and 7 the nucleus embnlifurmis is seen as a long thin sheet of gray matter separated from the dorsolateral surface of the nucleus dentatus by a narrow space already described. Its most distal end nearly occludes the hilus corporis dentati (I'ig. 7), while proximally it changes its form, becoming thicker and shorter, encroaching less on the hilus. It will also Ije noted (Fig. 5) that its axis changes; at first running dorsoventrally in its distal extremity, it comes to lie more latei'ally in its proximal ]iart. corresponding in direction with the dorsolateral wall of the dentate nucleus. This nucleus is practically sc])arate throughout its entire length, being the most definitely outlined of the accessory nuclei.

The nucleus globosus (Fig. 5) is also seen as a distinct oval mass of gray matter in its distal ]iortion, beginning a little above the appearance of the hilus. In its proximal end this nucleus is represented as fused willi the nucleus of the roof (I'igs. 5 and 1).

The nucleus of the roof appears in the reconstruction as a large irregular mass, distinct in its distal portion, becoming fused with the nucleus globosus in its proxinuil portion. The outlines of this nucleus are indefinite in this series, its ventral surface being in very close relation with the gray matter of the roof of the fourth ventricle.

DESCRIPTION OF PLATES XXIX-XXX.

Fig. 2. — View of dorsolateral surface of model of N. dentatus. Proximal end corresponds to top of figure; median line is to left. J/, mesial border; T, lateral border; ,1, B, C, J), Ji, are placed over primary fissures; n, b, i; d, e, over secondary sulci; /, is extension on to dorsolateral surface of tUe internal fissure of the ventromesial surface.

Fio. 3. — View of ventromesial surface of model of N. dentatus. Median line to rii;lit. 7, internal fissure ; L, lateral fissure ; i, internal lobe; i/i, median lobe; I, lateral lobe; H, bilus.

Fig. 4. — View of mesial border of same at right angles to median line. Relations of hilus to dorsolateral and ventromesial walls are shown. Distally the hilus is narrow, increasin;;- rapidly as one passes cerebralwards.

Fig. .5. — View of mesial border of N. dentatus with accessory nuclei in place.

S, nucleus emboliformis; O, nucleus globosus; S, nucleus of the roof; o, narrow space through which escapes UK^st dorsal fibres from MarkUern.

Fig. 6. — View of dorsolateral surface of same. Legend as in Figs. 3 and .5.

Fig. " View of ventromesial surface of same. Legend as in Figs.

3 ami 5.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL-MAY-JUNE. 1901.


PLATE XXIX.



Fig. 3.



Fig. 3.


Fig. 4.


THE JOHNS HOPKINS HOSPITAL BULLETIN. APRIL-MAY-JUNE, 1901.


PLATE XXX.



Fig. a.


Fig. 6.



Fig. 7.


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155


USK OF THE 3IATKIUAL OF TIIF DISSECTIXd ROOM FOI! SCIENTIFIC ITRFOSES.

By C.'iiAJti.ES i;i>--^i:i.i. Bardeen, M. D., A.ssoi'idh' ill Analiiiitij. J</liii^ IloiiIiHis I ' iii rrrsili/.


L'liseiiln'i'g. in ;i ruL-eiit iirticlr.' Ii;is failed atli'iitioii to ihe oj]|i(irtunitic>.s that the disseeting room offers I'or seientilic investiuation. He gives an interesting siunniarv of the various atteni]its that have been made to take advantage' of tlv s.' ojiportnnities. and calls |iartieular attention to the records obtained by Selnvalbe at Strassburg. by C'nuningham at Dublin, and bv tlie Anntonncal Society of (ireat l'>ritaiii and Ireland.



Fig. I.

It has seemed In me that the mctlinds employed In utilize the material of the dissecting room ami the work of the students for scientific purjioses in Professor MalTs lab(jratory at the Johns Ilojikins TTniversity, iialtimore, uuiy ])rove ol' interest, ]iossibly id' value, to those engaged rl.-c\vliere in anatomical instruction.

The immense amount of study that luis been given to thi' structure (d' the human b<idy during the last foui- ci'uturies reiulers it nnli]<ely that tlu' stiulent's initrained eye and hand could be utilized to advantage in a search for unrecorde 1


' Mi>r|'li(iluu:isr'lK's .Talnhiich, isii.i


facts of gross structure even if tinu' [lermitted him to delve in those little nooks and corners where the records are still incomjilete. The very considerable amount of variation, howevei'. which the individual liodies present in the structure, form and relatioiislii])s <>( their various organs, olfeis a rich field for cxdtivation.

Since tlie time of ])arwiu much attention has been given to the study of variations in plants and animals. The greater part of the attenticn. however, has been given to external features, to variation in size, color, and e-xternal fmni. Few studies have Ijcen made of the frequency of variation in the internal organs. Yet ]irobably the body of no animal is more suited to this study than that of man and none is studied with care by so great a number of indi\iduals each year.

Until couiparali\ely recently the variations brought to light by the dissector have lieen recorded only when of an unusual nature. These observations, however, have been so numerous that we may assume that most of the variations likely to be brought to light have previously been recorded. While the limits of variation of the various organs of the liody are thus fairly well understood, the fre(|ueucv of variations has Ijeen determined but for few organs and for them only incom]iletely. The true "'normal'" or "most usual" is unkniiwn. lleiile. in his anatomy, pictured tlud as nnriual which his experience led him to think the most usual. Most of the other leading anatomists have done likewise. No two books, otlier than comjulations from siuular scuii-ces, give the same account of the normal form of the various organs. The great ojijiortunity whicli the dissecting room olfers is that of determining the curve of frequency of the various {'(u-ms presented by bodily structures, and thus to make the normal a question of measurement rather than one of jiidguumt. To render this jjossible. accni-ate records of the ccinditions found in each body must be uuide. of such a nature that they may be afterwards compared and reduced to tables.

The method u( rec(U-d thus becomes a question of paramount importance.

In the Anatomical I/aljoratory at the Johns Hopkins Hniversity the first attemjits at making systematic records of conditions of structure revealed at the dissecting table were begun in tlu' fall <d' IS'i:.. It was determined to make a study (d' the variatiiuis in the <list ributioii of tlie ei'auial and s]iiiial nerves, especial attention lieiiig paid to the cervicoiu-achial and the lumbosacral plexuses. .\l the instigation of Professor JIall, Dr. .V. W. h'lting. at that time Assistant in Anatomy, prepared three record-charts, one for tiie nerves of the head, one for the nerves of the neck, arm and upper half of the thorax, and one feir the lower half id' the body. On these charts a iceord v\'as made (d' the sex. color, and aiie


as well as of the nerve distrilmtion in the body of tlie individual dissected. The seheme for recording the latter was as follows. On separate .successive lines the numerical designation of a given cranial oi- spinal nerve was placed, followed hy a list of the names of tlie nerves (o which the given main nerve li'unk was assumed to conti'ihnte. In the preparation of this table the standai'd anatomies were consulted. A few


The student.s were requested to compare carefully the nerves in the part dissected witli tlu' outline scheme, to unileiliuc Ihe names of those nerves wliich were found to coi'rcspond willi the sclu'me. to cross out the names of the nerves whicli did not thus correspond, and to insert these names in llic prii|iei- place. Complex conditions, such for instance as ai'c fmind in the cervicohrachial and the lundjo


Fui.


lines from the " ( 'cr\ico1ii-acliial Chart" may sulllce to make clear the general nature of this scheme:

C. VI. I'oST-liU. AnT-BU. _roST-TI10UAClC. SUISCI.AVIUS. SUPiiA scAP. Com. C. VII.

C VII- PosT-Bit. AsT-uit. — Extant TiioKAcic. Com-post. coud. Outer Cord. Musc-cut. — Vor-brai-h. Biecps. hr-ant. Ant. Post. OuTEii-ilEAP-MEDiAN. — Aiit-inUros. raliii-cut. Tliinnb-hr. .5 DiijitaU.

C. VIII. PosT-nu. AxT-mt. Inner Cord. Post. Cord. Sii!SCAPS. — Upjjir. Middle. Lcwrr. CiiicuiiFLES.. — Siip. Inf. Art. Muse. Spiral. — Musi: Int-eut. Ert-np-ciit-hr. A'.rt-lou<-cut-bi: Mnsc. Radial. — Exl-bi: Inl-bi-.t. 4. PoST-lNTEiios. — .l/"sr. .1/7. CoJi. 1). I.


saci'al plexuses, woe illustraled liy diagrams drawn on the backs of the charts.

These outline schemes were well arranged and Ihem'elically should have workeil well, '^'ei they did not prove a success in the hands of the students. The suggestion induced by print seemed continually to lead the student into reading the scheme into his "]>art." The task of verifying the charts thns became a severe one. Another diltlculty came from the fact tluit names can mean little so long as the '■ mirmal " is unknown. While the larger nerves arc so constant in position that the names cin'reut in the text-books


Ai'1!1l-May-June, 1901.


JOHNS HOPKINS HOSPITAL BULLETIN.


157


could be used without confusion it was I'diiud that many of the smaller nerves could he definitely rcennlcil nniy l)y attachiufj a sjieeial definition to the name, 'i'lic iliohi/iiof/aalric and the ijcnUocrural nerves may lie iiiciil inncd as examples. The value of these earlier charts lies rather in tlie ilhistrative diagrams of the plexuses placed on llie liaiks of the charts than ill the records made on the tabulation seiiemes.

Ill the fall of 1897 I undertook the iiniiiediaie sii|iervisiiin of these records. I discarded In a coiisidiTablc cxlcnt the use (if thi- ]iriiited schemes. The students were ciicouraLjed to record the distribution of the nerves by making free-hand


of tlie front of liie thigh; one for the sacral plexus; one for the })erineuiii; one for tlie back of the thigh, etc., in all 36 charts.'. Separate charts are used for the riglit and left sides (if the hoily.

In these diagrams tlie bdiu'S and the surface (lullinr of the body after the remciva] (if the skin and tlie superHcial fascia are indiealed by hue Hues |ii-inled in brown iii1<. The scale of the charts varies I'l-diii niir-balf to full bl'e size, according to the I'egioii to bi' charted. In this way the general average jirojiorf ions of tlie vari(nis parts of tlie body are furnished the student. JMarked variations from these proportions can



Fic.


diagrammatic sketclies to illustrate the cdndilinns found in the parts dissected. "Many of thi' drawings ihii,~ made were well executed. Yet few of the stmh'Uts are snnicieidiy skillful draughtsmen to make even these simple sketches without a, great expenditure of time. I therefore devised a si't ol' simple outline diagrams on which the nerve distribution can lie recorded. These diagrams are arranged for llu! various parts of the body. Thus there is one for tlir alHldiin'ii, which can hi> used cither for the nerves of the alMldiniiial walls cr for the liiiiihai' plexus (see Figs. 1-3); anotbci' fcir the nerves


readily be imlicaliil by changing the faint outlines of the skeletal scheme. .Vflci' removing the skin from a given part of the body the stiiclcnl draws on the appropriate diagram the course (if the superficial nerves as lie finds them running in the fas<'ia. When the muscles have been dissected out the ner\i.' supply of the various muscles is charted. Muscles and other slructures are drawn in to show the g<'neral relations of

- ■flii'si- cliiii-ts liMvr lirrn |.n li I i sliL'd ill iniiiiplili-t fonii; •' Oiitliiii'. lli'cnra Charts." ■flii.' J.iiins lloiikins Press, Baltimore, IHUO.


158


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. ] 31-12-2-123.


llic iKTvef!. The best ix-fovd.s have been obtaiiicrl when the student luis attempted to record only a few siiiipli' iimditidns nil a sinnh' chart. Tims in cliartini;- the nerves id' llir rnnil uT the tlii.^Ii separate eliarts are used to record the ihslrilui


J./" MS/,„


Fig. 4.

tioii io tile siiiii)rliis rnusck^, to tlie redii-^ muscle, to tlie dei'p c.i:teiisur muscles, to the adductur lo)i(jii.s muscle and the (jranlis. to the adductor lirevis muscle, and lo llu' addndur iiiiiijims and rxleninl ohlurator muscles.

To illustrate the method of using these charts a few ex


amples may be aiven. I'^ip. 1 I'cpresents the outline diafrram used For the alMhuiicii and the lumbar region. Fip. 2 shows the distribution oi the main ventral trunks of the abdinninnl nerves as dissected out and recorded by two students, fiu. 3 represents the lumbar plexuses and the distribution of the ' Ijorder nerves" found in the same subject. The lateral branches of the abdoininal nerves are shown in auntlu'r chai't (Fig. 4).

Of course one cannol hope to get from students the com])lete and accurate records which one could get by }iersonal di.ssection. It is cnily rarely that perfectly satisfactory records are ol)taiiied of (he [leripheral distribution of all the nei'ves. On the other hand, it would be a physical impossibility by personal dissection to get the same number of records in the same si)ace of time. Mistakes are more likely to be those of omission than of a jiositive nature. The student may destroy some fine nerve twig before it has been seen by an instructor, and thus it may csca])e record. The conditions that the average student finds and records are, however, of great value. Thus only may we ho])e to get that large number of records frcun whiih a curve of frciiucncy may be detei'inined.

In aihlition to the oi.tline diagrams I have devised a simple printed scheme for keeping record of the race, sex, age, size, skeletal peculiarities and marked variations from the normal in the various organs of the body. This latter set of records is made out Ijy the instructor who verifies the charts.

The verification cjf (he charts is one of the most important features of the undertaking. Without careful verification by one man who gives his time in the dissecting romn mainly, if not wholly, to this task the charts can be of little valu ■.

Active co-operation on the part of all the instructors and of the students in the dissecting room is also essential.

The conditions which at iircsent prevail in our nu^dical department render it also perhaps more than usually easy to get the co-operation of the students in carrying out work of this kind. The standards of admission to this school bring us a much nuu-e highly trained class of students than thos.' usually found entering the average American medical schocd. On the other hand, the routine of a graded com-se, while inferior as a method of education to that freedom of choice which nuirks the German university, renders it much easier to win the co-operation of the students in this work. The number of students dissecting each year since the beginning of the undertaking has averaged about one hundred.


O===N THE DEVELOPMENT OF THE HUMAN DIAPHRAGM===


In a paper on the development of the human cadoni, puljlislicd several years ago, I was not able to give a detailed description of the separation of the body cavities from one


' Mull, Jour, of Morph., vol. la, 1897


By Fhanklix P. Mall,

Professiir of Aiiuloini/. Johns Hopl-ins UniveisUy.

another, because the specimens at my disposal did not include all the necessary stages. For that study I used 19 human embryos between 2 and 2-1 mm. long, in which various stages of the development cf the body-cavities were shown, but a number of the important stages were missing.


Ai-eil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


159


During the past three years the collection of human euihryos in the anatomical laboratory has grown very rapidly anil all the missing stages for the study of the formation of the body-cavities have been supjilied. The following table gives a list of these embryos. It will be seen from it that

TABLE OF E.MBRYOS.




Time






tJrL'atost


between tln' be^innill;:' or tbe la.-^t period and


Direction




Ni).


lenji:th in mm.


of the seetion.


Fi


iin whom obtained.




the abortion.





XII


2.1


41 days


Transverse


Dr


Ellis, Elkton, Md.


CLXIV ...


3 . .5



"


Dr


MaoCalhmi,

Baltimore.


CXLVIII .


4.."


3S days


"


Dr


Hoen, Baltimore.


I.XXVI. ..


4.. 5



"


Dr


.Vliteliell, Cliieago.


LXXX ...


.5



(1


Dr


Brauham,

Baltimore.


CXXXVI .


5


.56 days


Sagittal


Dr


Campbell,

Halifax, N. S.


CXVI


6.5


5.5 days


"


Dr


Ryan,

SpringHeld, 111.


II


7


53 days


Transverse


Dr


C. O. Miller,

Baltimore.


CXIII


S



Sagittal


Dr


Gray, Washington.


CLXIII ..


9


5 weeks


Transverse


Dr


Lamb, Washington.


CXIV ....


10



Sagittal


Dr


Gray, Washington.


CIX


11



Transverse


Dr


Cusliing,

Baltimore.


CXLIV ...


14



Sagittal


Dr


Watson,

Baltimore.


XLiir ....


10



"


Dr


liookei',

Baltimore.


LXXIV...


li>



Transverse


Dr


Irving Miller,

Baltimore.


the series from 2 mm. upward is very complrir with the e.\ception of stages between 11 and 14 mm. long. Fortunately, the missing stages are not important. All the embryos given in this talile are practically perfect, the imperfect ones liaving been excluded. The present study is based u|hiii !•") embryos, only 3 of which are included in the 19 specimens considered ill (he earlier communication.

Il has often been stated thai Ihe development of lln diaiihrngin, i'S]i('cial]y in the Inmian embryo, is one ol' III!' iiiiisl (liHiciill |ii'ol)lenis of embryology, fiarty because (if the dilliciilty ill obtaining the iiecessaiy s|ii'ciiiii'ns ami partly heeaiisi' there are no fixed points rioni whiih In enleulate. Ill its (h'\i'loi)ment the wliole ilia|ilii'aeiii wiuiilers rrom the head (o the abdomen, passing Ijy as well as iiinilil'vino the structures and organs along the way. Sn. while vmi Baer recognized that the diapjliragm wandered in its development, picking up its nerve in so doing, a fairly clear pic tiiiv of the whole process was not given until Ilis studied eaicfiilhthe develo|iiiieiit of the iieelc, heart, lungs and intestine. In his studies His recognized the Aiihiijc of the diaiihiagin in a mass of tissue located with thi' liearl ainniiesl struct iiics lieloneing to the head and eonlaining within it the \'eiiis to the heart as well as the An/age of the liver, 'i'his mass of tissue ITis termed tbe septum transversuni. Ilis's studies


were made ui)on the human embryo, mainly by the method of reconstruction, and .shortly after they were published Uskow made a very careful study of the further growth of the septum transversuni. Uskow recognized the great importance of two additional structures in the formation of the pericardium and adult dia])hragm from the septum transversum; these he termed the iileuro- pericardial memhranc, containing the phrenic nerve, and the pillars which form the dorsal ends of the diaphragm. The pillars of Uskow have been termed the plcuro-periioncal memhranes by Brachet, and as the lattiT lei'in is more appropriate than the former I shall employ it in the present paper.

j\ly own studies show that the pleuro-pericardial and pleuroperitoueal membranes arise from a common structure, which extends from the lobe of the liver along the dorsal wall of the ductus Cuvieri to the dorsal attachment of the mesocardium. Ijater this structure grows towards the head to complete the jileuro-pericardial memlirane and then towards the tail to complete the pleuro-peritoneal mendirane. This stiiietnre, which I shall term the pulmonary ridge, is located in the sagittal plane of the body-cavity with cephalic and eandal horns on its dorsal side. The ductus Cuvieri lies between these horns (Fig. 29).

The purpose of this paper is to follow carefnlly the fate of the septum transversum and the origin and fate of the liulmonary ridge in the human embryo. In so doing il is of course necessary to consider the division of the body-cavity into the pericardial, pleural and peritoneal cavities. According to liis, the body-cavity in early embryos is divided into the Parietallwhle and Bumpflwhlen. The communicati-ou between these spaces he has also termed the recessus parietalis. The parietal cavity from its earliest appearance contains the heart and is destined to form the pericardial cavity. T shall term it the pericardial coelom. A portion of the recessus ]iarietalis forms the pleural cavity; it surnninds the lung bnd throughiuit its development and I shall term it the pleural eoeloin. The revnainder of the recessus |iai-ielalis to the origin of the liver has developed in it the liver and stomach; this is added to the general peritoneal cavity and I sliall term it the periloneal cculom. In the early embryos the whole eieloni lies far out of place; in F.mbryo XII nearly Ihe entire cadoin lies in the region of the head and iieek ami in the further develn|inieut of these parts the cadom with Ihe surrounding organs wanders away from the head to its |iermanent location. .\s long as the serous cavities arising from the codom are in tlu' process of wandering and are mil fnlly separated from one another I shall term them ]ileuial, pericardial and peritoneal coelom: when they are fnlly established I shall call tlieiii cavities.

Ill Embryo .\li, lig. 1, the cceloni of the embryo forms a fi'ee s|iaee eueiicling the heart and extending on either side of the body over the om|ihalo-mesenterie veins to the root of till' nmhilieal vesicle. This canal of commuuieation has ile\ elo|ieil wil hill il t he lung, stomaeh and li\'er, nml I hroiighoni its eai'lier ile\elo|iiiienl it measures in length ahoiit one-fourth of thai of Ihe hoilv (iMiibrvos XII, (IXLVIII, LXXVI,


IGO


JOHNS HOPKINS HOSPITAL BULLETIN.


[JJos. 121-122-123.


LXXX,, II and C'J.Xlll). The appearam-i' of the lun,;;- and liver marks the sul)divit;ion of the (•(I'loni iiiio the jileural and jjeritoiieal cadojii. W'ilh tlie dexeldpnient of tlie liver, limy and stomacli tlie e(eliini einilainiiiL;- them gradually dili:te>' until the emhryo is ahout !• nun. long, when the canal evaginate.s, so to speak, and Inrns the liver and stcnnaeh ont into the general pei'iloiienl cavity. The Wolllian liody, which (iniqiiod the dorsal A\all of this canal, gradnally degenerates and the Inng takes its place. From these statements it is readily inferred that the canal extending from the pericardial cceloni, Ilis's recessns parietalis. gives rise to the ]ilenral codoni on its dorsal side and to the peritoneal cielom on its ventral side. The line of division is formed hy the plenro-jieritoneal memlirane extending from tlic ductus ( 'uvieri to the adrenal.


am



Ar.



<•« 


0'

Fig. 1. — Pniiilc recmistnictiou of tliu eiiibryo 2.1 mm. loug. No. XII X liT times; m/i, amnion; iii\ optic vesicle; nc, auditory; vesicle hc, umbilical vesicle; h, lieart ; I'om, omi>lialo-meseuteric vein; mr, septum trausversum ; Oj, tUird occipital myotome; t'j, eiglitli cervical myotome.

The earliest emhryo in my collection in which the sejitum transversnm is well formed is No. XII, 2.1 mm. long, and about two weeks old." The specimen is very valuable for the .study of the beginning of so many structures that it also Ijecomes a good starting [loinl fur I lie study of the dcNclnpment of the diaphragm.

Figs. 1 and 2 give the external fcuin and oulline id' Ihe neural tube and alimentary canal drawn from a reconstruction. It is seen that the c(el(nH sends two canals into the


■-' Ditfereut pictures of this emliryo will be fimiul in the; .ImiiiiMl of Morpli., vol. 13; Ilis's Arcliiv, IS'.lT; .lolins Iloplviiis Hospital Hnllctin, IS'.IS; and the Welch Festschrift, .lohus llopkius Hospital Heports, vol. '.I.


head on either side of the neck which comniuiiicate with each dlhei- ill tile immediate neighliorhood of Ihi' nKUith. This U-slia|ied canal is sepaialed fidiii the exocielom on its ventral side by a Ijridge of inesodermal tissue connecting the umbilical vesicle with tlij embryo at the juncture of the head with the aiimion. It follows that this liridge of mesodernial tissue, the sepliim transversuni, is also U-shajied, as is shown in l-'igs. 1 an<l 2, iST and ilA//. ll forms a jiortion of the ventral wall of the pericardial cadom and sn]iports the omphalomesenteric and nmliilical veins. Sections of it are shown in Figs. 3, 4 and 5, which are from three sections through the head end of this embryo in the neighborhood of the first cervical myotome. The Aiilage of the liver is shown in Fig. t. which is located in this stage in a region belonging to the head.



>>„


'C


o


Fui. 2. — Parlial dissection of the reconstruetiou of the embryo 2.1 mm. long. No. XII x 37 times; dm, amnion; m, mouth; Hi', Br", lirst and second braneliial pockets; /, thyroid; p, pericardial coelom ; .■i^ septum transversuni ; I, liver; kc, nQibilical vesicle; /«•, neurenteric canal.

Figs. G to 9 are from an emhryo (CLXIV) slightly more advanced in development than No. XII. The embryo is from an ovum measuring 1 T x 17x111 mm., found in the uterus at an autop.sy. W'lii'ii the uterus was cut o])en the knife entered the ovum and |Hissil)ly distorted tlie emliryo, for when it came into my hands it was foimd that the emliryo was lloating in the cavity nf Ihe ovum Imt il was still adherent to its walls. This mechanical injury iindoiilitedly caused the body nf the embryo to straighten and at the attachment of the iiiiibilical vesicle the body <if the embryo is bent towards the \entral side, as is the case in a number of the His embryos (for instance, I'>H). The ventral wall over the heart, was also slightly torn. The entire uterus and ovum had been


ArRIL-MAY-JuXE, 1901.


JOHNS HOPKINS HOSPITAL BULLETIN.


161


liTcservod on ice fni' 2[ linurs, mid wlicn it was jiiven io iiie Iiy l»r. ^lacCalhiiii tiic i.'iitiic s|MMiiiic'i\ was iila<Til in sti-on>^ formalin. The si't-tioiis dl' tlic ciiilirvo sliiiw thai the tissuesi ore slightly iiiaceiTited Imt in i^cncral they arc well ]ire?orv<'(l. The spinal ecinl is (■l(ise<l ihnui.uhont its extent Iml thi' iiourcniore is still open. The thyi'oiil iiland. ii]i(ic and otic



UV


'W


Fig. o. — Section tlirougU tlic lirad <if tlie embryo '2.1 mm. loiii;-. No. XII X 50 times; rue, coelom ; /</i, pluiryiix ; /, liver; xl, seiitum transversura ; irr, umliilic.il vesicle.

vesicles, heart and veins, are but slightly more developed than ill N^o. XII. If this enihryo were curled up as No. XII it would measure froni 2.5 to 3 mm., whih' if the two had lunn hardened in the same way (Xo. \ll was hardciicil in ahohdl) they would ])rolialily measure alike.



Fig. 4, — Section tlnnnu'li tlie tliird occipital myotome of the cmhryo 2.1 mm. Ions. -"I mm. nearer llic lail tlian Fii;. 11 x .">(! times; (l.j, tliirel occipital myotome ; c«c, coelom ; /■, vein ; .■</, septinn transvcrsnm ; !, liver; pli, pharynx; "c, umbilical vesicle.

The figures given sliow the general relation as sei'ii in I'lmliryo .Xll with e;u-h id' the st laict ui'cs hut slightly iuhaiii-ed. The septum transversum is much the same as it is in .Xll, while the pericardial co'lom is puslied more to the ventral side of it and (he diverticidinii to tnini the liver is more marked. The iindiilical vein has extended somewhat (Fig. 9) and the jugular vein has made its appearance (Fig. T).


The tissue of the septum transversum in the two embryos is formed of irregular round cells, between which there are numerous vessels, of irregular diameter, which commnnicate freely with the veins to the heart.

The next stage of the develupment of the septum trans


'A ' ' !'


3-^-c.


Coe ;'




■^vu

(-VOM


Fig. 5.— Section throusli the first cervical myotome of the embryo

i.l mm. lonic, .'IS mm. nearer the tail than Fiir. 4 x .iO times ; f\ lirst cervical myotome; toe coelom ; ;■», umbilical vein; ;"'/», omplialo-mesenterie vein; iiiiib, umbilical vesicle.

versnm is found iu an embryo 4.3 mm. long (CXLVII), obtained from llr. Iloen.' The specimen is perfect and normal, as it was obtained through uiechanic;il means. The entiro



(S^^-:^


Fig. (i. —Section throun-h the head of the embryo 3. .5 mm. long. No. CLXIV X .'iO times; y</(, pharynx ; i«, bullius aortae ; cc/j/, ventricle.

ovum was hardened in S(i |ier cent alcohol shortly after it was expelled from the uieiais. This of course fi.xed the embryo in its natural shape, as was the case with No. XII. iioth embryos are cnrved, but in the emliryo 4.3 mm. long the lii-aiiehial region occupies relatively more space than it


'A photograph of this embryo is given in the Welch Festschrift.


1(52


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nds. 121-122-123.


does in the embryo 2.1 mm. long. In proportion to the length of the embryo.? this distance h;is inerensed 3 times, Tlie pericardial cfrlom has receded i'roni the head in |)r()]iortion to the inerenso of the growth of the branchial arches. In the emliryo 2.1 mm. long i\\v kead end of the |ici-ieardiai crelom is oiiimsHe (he otic vesicle, while in the end)rvo 1.3



Fig. 7. — Section tlirdiiuli tlu' embryo o..5mm. loiiir. .14 mm. nciirur the tail tb.au Fis;. x ."'O t mcs ; p/i, jiljai-ynx; lui, auricle; rent, venfiicle; .■it, septum tr.ansversum ; <;/, jugular vein ; /'», umbilical veiu.

mm. it is o])]iosite the first occipital myotome. The puint u\' comnnmication between the peritoneal coelom (encircling the liver) with the exococlom has also receded. In the embryo 2.1 mm. lung it is opposite the second cervical myotome; in embryo 4.3 mm. long opposite the second tlioraeie myotome



Fig. S.— Section tlirougb the embryo S.6 mm. long, .'2 mm. nearer the tail than Fig. 7 x .50 times ; I, liver; wiit, ventricle ;.«»■, siuus renuieus; coc, coelom.

(compare Figs. 1 and lU). Ilis's embryo Lr (4.2 mm. Imig) is intermediate between the t\V(i embryos just compaicil. In Lr (see liis's Atlas, Pis. IX and XI | llie ]ierieardial. |ileural and peritoneal creloni encircling tlie liver extends from tlie first occipital myotome to the sixth cervical, and the omphalomesenteric veins jirotrnde into these canals of the co'lmn. The liver has extended into the septum transversnm but does not yet encircle the omphalo-mesenteric veins as it does in


my embryo 4.3 mm. long. This detailed descri])tion is given to show the fate of the ccelom ' of the hea<l and neck. It gives rise to the pericardial and ]iit'ural cavities, and tliat portion of the ]U'ritoneal cavity encircling tlie liver of (he adult. Sections of the embryo 4.3 mm. lung ( Xo. C.XIjVIII. Figs. 11 and 12) show the livei' sprouts growiiio' in all dii'cc


FiG. 9. — Section through the embryo 3..'> mm. long, .is mm. nearer the tail than Fig. S x .50 times; rvw, coelom; ii:l, intestine; rum, (^mphaln-mcsenteric vein ; /■//, umlulical vein.

tious tlinuigli the sejitum transversum. encircling and ramifying through the omphalo-mesenteric veins, making a condition slightly in advance of that in Ilis's embryo Lr. The sections of this embryo show clearly that the heart, lungs, liver and li'Wer peritoneal cavity arise in tissues surrounded by that portion of the cadom extending into the head in Embrvo XII,



Fig. 10. — Outline of the embryo 4.:! mm. long. No. CXI.VIII x 1.5 times. ,, first cervical myotome; r',, ei!?t cervical myotome, 'llie line imlieates tlie dii'ection of the sections.

Fig. 1. Fig. 11 is taken from a section through a plane cutting the root of tlie arm and the otic vesicle, and can readily lie placed in the outline, I'ig. 1(1. It is seen that the lung.-arise wlicre the pericardial ecelom goes over into the pleural, /. ('. high up in tlie region of the head. Immediately on the dorsal side of them is the beginning of the lesser ]ieritoiieal


' Kopfbohle ; ITalsboble; I'arietallioblc ami recessus |i;n-iel:ilis.


Ai'hil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


163


cavity, and the intestinal tnbe struck in this section is the stoniacli. All these stnietnrcs lie on the cephalic side of the first cervical myotome. Projecting into the peritoneal ccelom, encircling and penetrating the omphalo-mesenteric veins are the projections of the liver. Figs. 11 and 13, L. The two lohes rrai-h I'rom the tip of the Inngs ami the foramen of Winslow to the point wliere the entodermal cells of the liver arise from


X







ryj)


YC


n


Via. 11. — Section tlirougb the embryo 4.3 mm. Innsr x 2.5 times; T,, lirst tlioracic myotome; C, C,, and (\, cervical myotomes; .s', stomacli ; fti, brdnchus; /i, heart; (, thyroid; /<■•, pericardial cavity; I, liver; />, foramen of Winslow.

llic aliinentaiy canal, or in this ease the iluodcimm. The lobes of the liver lie entirely within the canals of the coelom on either side of the head. The caudal ends of these coelom canals have migrated from opposite the second cervical myotome ill Emliryo XII, Fig. 1, to opposite the second thoracic




.. ^T^


/




UV /



J



-'#^^


-5^)/,



L *



■-■/


Fig. 12.. — Section throush the embryo 4.:i mm. loun, .4 mm. deeper than Fis;. 11 x 2.") times; /, thoracic myotomes; ;, intestine; /, liver; /', ventricle; bii, bulb of the aorta; nm, amnion; iii\ umbilical vein.

myotome in Embryo CXLVIII, Fig. 10. It has moved towards the tail eight segments, while the cephalic end of ilie canal, the ]iericardial ccelom, has been kinked over to correspond with the bending of the head, has dilated to correspond with the growth of the heart, and has receded from the otic vesicle to (lie extent of the gi'owlb of I he linincliial arches. We have in this embryo the necessary stage to Imnte tlie organs which arise in the neighborhood of tin; sepiiim tiaiW'


versnni, as well as to give the fate of the ccelom in their immediate neighborhood.

A stage somewhat in advance of CXLVIII is ]A.\^M. The embryo is slightly larger, measuring 4.5 mm. in greatest length. It was obtained from the uterus 7 hours after death. The entire ovum was placed immediately in aljsolute alcohol.




Fig. 13. — Section through the embryo i.n mm. long. No. LXXVI x 2.5 times; /'c, cardinal vein; l/jc, lesser peritoneal cavity; <lc, ductus Cuvicri; xc, sinus vcnosus.

It was impossible to obtain a picture of the embryo before it was cut. but the specimen proved to be an excellent one. The direction of the sections is more nearly transverse than



l


H


Fig. 14 Section llirougli the embryo 4.5 mm. long, .il nnn. deeper

than Fig. IS x 25 times; we, cardinal vein; u, aorta; nnii. omphalomesenteric vein; fii, umbilical vein; /i, heart.

in CXLVIII. In CXLVIII the neuropore is closed with a thickening of the e|iidermis just over the point of closni'e; the umbilical vein entei's the liver and its direct connection with the ductus ('ii\ieri through the body wall is cut oil'. In LXXVI the neiiid|ioic is completely closed and the eiiilii'yo is somewhat lai'ger than hefore (compare Figs. i:i and I I with II and 12); the umliilical vein, however, coiiiniiinieates with I ill- (liictus Cuvieri tiirough the body-wall on the left


164


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-1^2-123.


side. This Ls an instaiifc nf rctardcil (li'vclii|inii'nt of a part, as tlie left iimliilical vein t^liniild lia\r \alli^lu■d liy lliis time. Fig. 13 gives a seel ion lliniiigli llie tdi-anien nf Winslow imniediately on tlie caudal side (if tlie lung liuds. as shown in a lateral view of the nuidel of the eniljvyo. Fig. 1-"). The



Fig. I.


se]ituni transversuui and liver have increased in fpiantily. as a e(nn|iarison of tlie dilVerent tigui'es will show. In tliis



Fig. 1G.

Figs. 1.5 .iiul Ifi. — Riirlit aud left views o( ,t roconst ruction of the embryo 4.. T mm. long x 2n times; n, aort.i ; ph, pli;ir\ii\ ; Im, hulbus aort;e ; me, coelom ; /), purieardiiil coeloin ; /, lung'; li, liver; Wb, Wolffian body ; ■«, stomach ; ./>, foramen of Winslow ; .«■, sinus veuosus ; "I, septum transversum.

stage we have the extreme bending of the head, which throws 'the heart to its most ventral ])oint with the septum transversum aliout parallel witli long axis of the embryo. The

PC DC



Fig. it. — Lateral view of the reconstruction of an ciuliryo .5 mm. long. No. LXXX x 17 times; I, hinir; li, liver; s, stomach: dc, ductns Cnvieri ; pr, pericardial coelom which communicates fully with pi euro- peritonea I coelom.

position of the heart, lungs, liver and their relation to the cadom is much the same as in the younger embryo with the


exception of the lesser ]ieritoiieal cavity, which is now more to the i-audid side i.if the limits.

While ill the embryo 4..'! uini. long llie niyoiomes were well formed and hollow, in the iMuliryo 4..") they are solid and contain embrvonic muscle ii'nes. The dorsal ganglia are also



._DC



Fin. Its. — Section through the nceU and heart of embryo LXXX x 2.T times; ,, fourth cervical nerve: iv, cardinal vein; </(-, ductus Cuvieri; Of, oesoi>liagus ; //-, ti'achea : .sr, sinus renniens.

more developed. In the I'lubiyos ."i mm. long (LXXX and ('.XXXVI) the myotomes are still further difTerentiated with nerve tiimks. composed of lioth dorsal and ventral roots, which are growing into the body-walls of the embryo. Figs. IT-.'O give the general form of this embryo, in reconstruction





Fig. 111. (Section through embryo LXXX .:.'•_' mm. deeper than Fig.

IS X ;i.") times; C, fifth cervical nerve ; fv, cardinal vein ; .i, subclavian vein; ih; ductus Cuvieri ; I, lung; pli, phrenic nerve.

as well as in section. The se]itum transversum is not as perpendicular as in either younger or older stages (LXXVI and II), but in general this embryo is intermediate between them. A separation between the jiericardial and ]ileural ca^lom now Viegins to make its appearance by means of a constriction in its walls, the ductus Cuvieri encircling the cwlom at this point. The hing buds hang free into the pleural ccelom,


Apkil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL 15ULLETIN.


1G5


iiiul the liver and stomacli into the peritoneal eo'lmii. Tli.^ dnctus t'livieri lieb in a riilue of tissue eneirclini;- tiie lanal di coniniunieatitin lictween the pericardial and pleiiial iddniii. In this eniliryo the ridge has no mesentery, as descrilied by His {V\g. 18), hut in sagittal sections of the same stage (CXXXVI) tlie mesentery is yiresent. As yet there is no




KiG. 20, — Section tlirousili embryo LXXX, .2(i mm. deeper tli;iii Fiij. li) X 2.5 times; <',.,. si.xlli cervieiil myotome; <i, aorta; iv, eardiual vein; .«, stomach; ", iiinljilical vciii ; //«•, lower peritoneal cavity.

indication of a line of se|iai'ation between the plciiial and peritoneal cceloni in LXXX. Imt in ('XXX\'l ihei-e is an elevation on the d(ii>;d wall (d' llie |il('iiial cii'lniii, lig. 21, wliieh encircles the long ami joins the dnrsal end of the s('|itnni li'ansversniii, 'i'his is one of the ]iillars of Uskow



FiG. :ll. — Sa'jiltal section tliroii2;li an embryo, ."> mm. lonii;. No. CXXXVI X 2'} times; /i, lieart; i-i\ cardinal vein; xl, septum transversuni ; ', hoii;-; .s, stomacli; k, arm; jir, pulmonary rid:;'e.

(ir the beginning <>( a ridge which I shall term the juiliiioiiiiri/ ridi/e.

Fig. 20, coni]iared with Kig. 1o. shows that tlu> foramen ol" Winslow has moved more lapidlv Inwards liie tail than the Iieart. A section through it strikes the heart sqnarely in one case, while in the nther it does not tmieh the heart hwi strikes the li\cr mily. This is in [lai't i\\tt' ti> the direction of the sectiiiii in thi' Iwd specimens, and in |iiii'l to the shifting of till.' fdrameii uf Winslow with (lie recession of the


stomach. The cervical nerves are sefiarated in No. LXXX with the exception of an anastomosis lielween the fourth and the liltli. j-riim this piiint the pliri-nic nerve arises. Fig. 19, and passes to the lateral side of the parietal ccelom and lung. In a later stage it reaches the se])tum transversum through the plenro-]iericardial menilirane of I'skow.

I have now followed the transformation of the relatively sim]ile C(el(iiii of the head and neck from the time it is well I'diiiied ill an embryo of the end id' the second week to the end of the tiiird week. During this time tiie pericardial cadom has moved away from the head and the pericardial cavity is well lUitlined. but the membranes which divide the ccelom intii pcriearilial. pleiiial and jieritnncal spaces have not yet



FiQ. 'J2. — Rccoustnictiou of embryo No. II x 30 times; 7>, bronclins; X, liver; P/i, plirenic; 1, ,?, ,?, 4 branchial pouches.

appeared. During the foui'th week both of these membranes a]ipcar, but llicy are not well delined iiiilil the fifth week.

Fig. 22 is from a profile rcconslniclinn of I'hnbryo 1 1, showing the relation of the organs to tme another. A cast of the colon of this embryo is given in Fig. 23. The extreme ventral kinking of the heart is shown in this stage and from now on it begins to sink more and more into the body as the liver recedes, 'i'lie cinnmunieation lictwecii I lie pericardial cielniti and the |ilciiral eoelom is reduced to a narrow slit lietween the Cephalic end of tlie lung bud and I lie iliictus Cuvieri. It a)i]iears as if a simple adhesion of the walls of the slit would. com|ilctr the closure of the pericardial space. Fig. 24 is a .section Ihroiigh this space, striking the seventh cervical myo


16G


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-123-123,


tome and the tip of the phrenic nerve. It shows that the nttachnient of the ductus Cnvieri is no longer hroad, as in rnibrvd IjXXX, Ijiit is narrow, formino- a mesentery as de


fiG. 23. — Cast of coelom of embryo II x 20 times; /', perieiirclhil coelom ; L, coelom encircling to liver.

scribed by His. On the dorsal side of the ductus there is a ridge wliicli liegins as tlie ductus projects into the coelora and gradually I'luis over into tlie lobe of the liver. Tliis ridge is very pi-ononiiced and is also well shown in llu> sections of


CV



-:^^4-U


Fig. 24. — Section tlirousb the seventh cervical segment of the embryo 7 ram. long. No. II x 2.5 times; ('., seventh cervical myotome; rv, cardinal vein ; ili; ductusCiivieri ; ?<)•, brachial iilexus; /(/•, pnlmi>?i;ny ridge; ///(, jihrenic nerve; h, bronchus; h, heart; hn, bulbns aorta'.

His's emljryos. A and 1>, as given in his Alhix. The relation of this ridge to tlie phrenic nerve as well as its form in older endiryos makes of it the Anlfuje of both the pleuro-])ericardial and pleuro-pcritoneal membranes. It lies in the sagittal plane


of the coelom and as it passes the region of the fourth and fifth cervical noi-ves receives into its substance the phrenic nerve which ]iasses on tlie caudal side of the ductus Oiivieri. Soon the lung bud grows against this ridge, causes it to bulge. and with the rotation of the liver towards the head the ridge



Fig. 35. — Section through the embryo 7 ram. long, .6 ram. deeper than Fig. 24 X 2.5 tiraes ; T,, first thoracic myotome ; ci\ cardinal vein: Tl'fi, Wolffian body; .<:, stomach; Ipc, lesser peritoneal cavity; ?, liver; //, heart; kI, septum transversum.

is divided into two parts; (1) the cephalic end which retains the phrenic nerve and ductus Cnvieri and forms the pleuropericardial membrane, and (2) the caudal end which remains attached to the tip of the dorsal end of the septum trans


Ph :'^



-y7'


^h


fr'


PR


, ^ Li.


Fig. 26. — Sagittal section through the embryo (>..5 mm. long. No. CXVI X 25 limes; /jA, ]>haryn\; /j/-', first branchial arch; 6'(, bulbns aorta'; (f, auricle; /'. ventricle; ^ Inng ; //, liver; />i\ pulmonary ridge.

\ersum and the liver mi the one hand, tlie body-wall on the other, til f<iriii the ]ilcui(i-|ieritoneal membrane.

Figs. 26-28 show tliis ridge in sagittal sections in Embryo rXVI. a specimen not (piite as large as No. II, but somewJiiit


Ai'eil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


IG'i


more advanced in developnu'iit. In P^ig. 26 its cephalic end a])])ears as a broad menibiaiie which in a section nearer the middle line extends to the liver on the ventral side and'



k


^


^ L'.v


\^^:v>^:v.^>^^


vs-^^v


y^PR


A


Fig. 27.— Section tliiougli tlic embivo 6..5 mm. louir, .1 mm. deeper than Fig. 26 x 2.5 times, /i/i, pbarvux ; <(, arm; pi; ijulmonary ridge ; I, luug.


it begins to widen at its dorsal end hand in hand with tlu rotation of the liver. Fp to this time the se]itnm transversnm is pai-allel witli the vertebral eohimn. with the heart


a


H





i^i^


wb'pr" "~"'

Fig. 28. — Section tlirough tlae embryo 6..5 mm. long, .13 mm. deeper tliau Fig. 27 x 2.5 times; <«■, oesophagus; n, aorta; I, lung; li, liver; 11'/), Wnltliuu body ; jir, pulmonary ridge.



Fig. 29. —Lateral view of the iniliiionary membrane and surrounding parts of the embryo 7 nun. long. No. II x 30 times; «, auricle; , ventricle; /, lung; /(, liver; II A, Wolllian body; ///•, pulmonary ridge; ., eighth cervical myotome.


aecoiMpaiiics the ductus Cnvieri to the body-wall mi tlic dorsal side, I""ig. 21, pr. Stil more towards the midlino the ridge ends as a decided elevation iiuiiicdiately to the eainhd side of the ti]) of the lung.

After the lailnionary ridge is well formed (as in I'hnbryo IT)


on its venti-al siiU' ami tlie liver on its dorsal side projecting into the ]ici-itoiieal eodom, as shown in No. H. This eondition was hruught about at the time of the bending of tln' head when the viscera were forced towards the tail and into this position. The cejihalie end of the pericardial crelom


168


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


is tluis Lent over the septum transversum but the nuiin part of the head (•<vloiii remained parallel with the si)iiial eoliiiiin on either .side ol' llie liody. This process may he termed tlu: rolling over of the heart.

In the next stage the heart rolls in a dorsal diret-lioii and the liver in a ventral direi-lion. 'i'his process has already hegnii in endiiyo CLXIII and C^XllI. In so doing the lung buds become Ijuried deeper in the body of the embryo and the liver gradually changes its |iosilion from the dorsal side



Fig. 30. —Lateral view of the pulinoniiry membraue and siinomuliii!;parts of tlie embryo '.I mm. lont;; No. CL.XIII x 13i.< times, (\, eiiihtli cei-vical myotome; //.liver; I, liiuir; ■■-■, stomach; 1I'6, Wolfliaii botly ; y>/(, plirenic nerve; y«', pleuro-perieardial membrane ; ^/yj. pleuro-peritonuMl mcnihraue.

of the septum transversum to its ventral side. The septum transversum undergoes almost a half-revolution. The cudom containing the liver lobe evaginate.s and becomes incorporated with the general ahdiuniual ca\ity.



I'"iii. 31. — Section through the filth cervical myotome of the embryo '.I mm. Icing, No. CLXIII x l-}^ times; (',,, llfth myotome; (•<■, cardinal vein; tir, ductus cuvieri ; br, brachial ple.xus; jih, phrenic nerve; /ir, cephalic end of the pulmonary ridge forming the beginning of the pleuro-pericardial membrane.

\\'itli (lie rolling of the heart the cielom connecting the pericardial with the pleural space is kinked at the points of juncture between these cavities. At this point the duct of ( 'uvier enters the heart. Soon fi-om its dorsal boi'iler the ]nihnonary ridge arises which is semicircular in form and reaches from the liver to the dorsal walls of the credom as ilescribed under I'hid.iyo II. It is shown in section in Fig. 'H, and in a lateral reconstruction in Fig. 20. The pulmon


ary ridge is really an extension of the septum transversum from the lobes of the liver to the tij) of the AVolffian body. ,Vs the heai-t nio\'es in the dorsal direction and the liver in the ventral dii'ection it is the dorsal end of the septum trans


'^•^'HCoc/— -^ ^^e^, — ' — Ph


PCoe



Fig. 33. — Section through the embryo '.I nun. louir, -Wi mm. deeper than Fig. 31 x 12,'.; times; ('„, si.xth cervical myotome; •■/•, cardinal vein; p/i, phrenic nerve; jjc, pleuro-pericardial membrane; ////, plcuroperitoneal membrane; pl-cve, pleural coeloni ; /j-mc, peritoneal coelom.

versum which moves most ra])idly in the cbrection of the tail. In so doing the pulmonary ridge grows rapidly and divides at its dorsal end into two memtiranes, one containing the



Fig. 33 Section through the embryo '.I mm. long, .10 mm. deeper

than Fig. 33 x 13)^ times; C^, eighth cervical nerve; pp, pleuro-peritoueal mcmbi-anc.



Fig. 34.— Section through the embryo !) mm. long, .84 mm, deeper than Fig. 33 x 13).^ times; y,,, third thoracic myotome; //«■, lower peritoneal cavity ; 117), Wolfliau body.

duct of Chivier ;ind phrenic nerve, and the other still encircling the lung bud. In this division we have the beginnings of the jdeuro-pericardial memhrane of ITskow, and tlie pleuroperitoneal mendjrane of Brachet.


Apiul-May-June, 1901. J


JOHNS HOPKINS HOSPITAL BULLETIN.


IGi)


'Pill' iiiiliiiiiiiary ridpo is well formed in Embryo II. It appears as a ridge of tissue passing towards the head from the lobe of the liver on tlie dorsal side of the ductus Cnvieri and then aloui;- th.e dorsal walls ol' the rcrhim to the meso





^f."-'



^LPC


Fig. 3.5. — Sagittal section tlirnuijli the unibrvo s nini. loiii:. No. C'XIII x 10 times; J, lower jaw ; .s-^z-uc, siuus lu-aecervicalis ; ;, fouitli cervical nerve, /)/(, phrenic nerve; st, septum transversuin; ih\ iluctus Cuvieri ; /)<•, pleuro-pericarilial membrane; pp, pleuro-peritoiieal membrane; /, lunif; ,v, stomach; 'yjr, lower peritoneal cavity ; T'/i, Wolffian body.

(■ai-(liuiii. \\liere it ends in the pillars of Uskow. As the einhryi) gidws larger tlie ductus t'uvieri separates more and mnic friiiu the latei'al liody-^all. and in a incasurt' sliifts intn the [lulmonary ridge, whieh at its nidst emne.x point grows in the form of a ridge towards the heart. This secondary ridge, which is present in C'LXIII. linally se|)arates the ]ilenral from the pericardial cavities and comiiletes the jilcnro-pericardial membrane.



Ki<i. :i(I. — Section through the embryo S mm. lony nearer the mitldlc line tliau Fiif. 3.5 x 10 times; ;/'■, ductus Cuvieri; I, lung; .«, stomach; Pli, pleuro-peritoncal membrane.

Tile piilniiiuary ridges from thcii' beginning to tlieir separation into the pleuro-pericardial and pK'urn-pri'itcnu'al niemliranes a]ii)ear as two ears to the se[)tum transversiun, c-\tending along the ducts of Cuvier in tlie sagittal plane id' the body and at right angles to the phiiie of tlie septum trnnsversnm. Judging by tlie relatimi n\ the phrenic iier\c to the ])ulmonary i-idge tlie poi'tion (d' it I'n tlie dorsal siih' (if the ductus Cu\ieri Clint, Lining the phrenic nerve, the pnrtimi containing the ductus Cuvieri. and the sccimdaiy ridge nf the


ventral side of tlie ductus Cuvieri, form the pleuro-pericardial membrane, 'i'he portion of the pulmonary ridge on the caiuhil side nf tlie ]ihrenic nerve gives rise to the pleiirnperitiiiie;d mend ii a lie. In so doing it gradually shifts over


PP


■Sl;


Fig. S7.— Sagittal section through the embryo 10 mm. long. No. CXIV X 10 times; /(/j, pleuro-peritoneal membrane.

the lung hulls and iinally t'omplctely separates the jileuial rriiui the peritoneal cavities.

The growth of the plenro-pericai'ilial meiiihr;ine towards



Fig. 3S. -Lateral view of the embryo 11 mm. long, showing the pleuro-pericardial and pleuro-peritoneal membranes. No. CIX x S.'.j times; /-, lirst rib; /, lung; 11, liver; p/i, phrenic nerve in the pleuropericardial memljrane; .s, stomach; ir6, Wollliau body; (ip. pleuro-peritoncal membrane which is not quite completed.

the head ami the ]ilenro-peritoneal towards the tail widens the dorsal projection of the septum transversuin and iiiin this wide hasi' the lung Ijurrows throwing the jileuro-ii.'ricard-ial membrane with the phrenic nerve to its medial side. The fate of the pulmonary ridge is shown in Fig. 3(1. which is from lOmbryo CL.XIII. Sections of this embryo are shown in l-'igs. 31 to 31. They show again that the pulmonary ridge reaches rroiii the diietus Cuvieri to the ti|i of the lung, and the phieiiie nerve. It is readily seen from Figs. 30 and


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JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. iai-122-123.


o2 liow the ])lirenic nerve is pushed to its permanent position liy the further rotation and recession of tlie septum (ransversum and livei'. ajid the lateral growth of the lungs to encircle the heart.


PC .


"it \



iMmMiK




Fig. 30. — Section through the body of the embryo 11 mm. long. No. CIX X 10 times; /i/i, plirenic nerve; yjc, pleuro-pericardial membrane; .s7, septum transversum ; //. humerus; .;, tirst rib; .', second rib; /, third rib.

Figs. ;J.j and 3lj are from sagittal sections of iMnlu-yo (.'XIII, which is of the same stage as CLXIII. The iihrenic nerve is shown throughout its whole course from the fifth cervical nerve to the pleuro-])ericardial memhrane. The nerve receives a second hi'anch a few sections deeper frmn the sixth cervical which unites with the main trunk hefore it enters



(^


.f W-^



/


?h/


\y:^


" ^ -S[


Fio, 40. — Section through the embryo 11 mm. Ion;;; .IS mm. deeper than Fig. .39 x 10 times; /;/<, phrenic nerve; st, septum transversum; P'-, pleuro-pericardial membrane; pjj, pleuro-periloneal membrane; J, ,.-', ,)', 4, ribs.

the pleuro-pericardial nienil)rane. Hanging from the pleuropericardial memhrane is a section of the pleuro-|ieritoneal, which in Fig. 36 unites with the dorsal wall of the cndom at the head end of the Wolffian body.

About this time the portion of the ])ulinonary ridge des


tined to heconii' the plcuro-]ieiicardial membrane unites with the root of the lung hud and com]iletely closes the pericardial cavity, Fig. 37. By this union the course of the duel us Cnvieri is from the body-wall to the heart throtigh the pleuropericardial mendirane, and the plane of the pleuro-pericardial



Fig. 41 Section through the embryo 11 mm. long, .46 mm. deeper

than Fig. 40 x 10 times. The pleuro-peritoueal membrane is incomplete on one side, .;, j, .7, i:, ribs.

membrane is jiractically that of the septum transversum, the two together being transverse to the body of the embryo. The phrenic nerve at this time is in the plane of the septum transversum and reaches its dorsal tip through its projection, the pleuro-pericardial membrane.

Immediately aftei the completion of the pleuro-pericardial


v3^^^



V^-^'


Fig. 42. — Sagittal section through the embryo 14 mm. long. No. CXI.IV X 10 times, ///>, phrenic nerve; /'/, tenth rib; .s, stomach ; /,-, kidney; 11', Wolllian body.

membrane the rotiition id' the liver and septum transversum is accelerated, and by the time the embryo has grown to be 11 mm. long (CI.X). tlie liver is practically in its adult position. The rapiil rotation of the liver, especially at its dorsal end, has elumged the relation of the planes between the


April-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


171


pleuro-pericardial membrane to tlie septum transversiim from parallel to right angles. Now the septum transversum is in ^ the plane of the plenro-peritoneal membrane (Fig. 38). With' the recession of the septnm transversum, especially at its


i


\^ -'


'L


rU


PP-: <PP


>i




■J 3


Fio. 43. — Section tlirough tbe opening between tlie pleur-il and peritoneal cavities in the embryo 14 mm. long x .'50 times; .s, stomach; I, hing; /<p, pleuroperitoneal membrane; nr?, adrenal.

dorsal end, the evagination of the co?lom containing the liver and stomach is complete, throwing them into the general peritoneal cavity.

Figs. 39, 40 and 41 are sections through the plenro-peri


■ mi




M \


Fio. 44 Sagittal section through the body of the embryo 10 mm.

long. No. XLIII X 10 times; .9, ninth rib.

cardial and plenro-peritoneal membranes of Embryo CIX, Fig. 38. They give the relation of the pleuro-pericardial and plenro-peritoneal membranes to the surrounding structures. The heart is now in its permanent location in the thorax and


the liver is in the abdominal cavity. The septum transversum with its extension, the pleuro-peritoneal membrane, stretches across the body from the tips of the embryonic ribs. But in the thorax lie the lungs, and their further growth into the lateral walls of the embryo and septum transversum will make them encircle the heari:, thereby enlarging the pleuropericardial membranes and changing j)osition of the phrenic nerves.

After the heart, lungs, liver and stomach are located in their permanent positions the plenro-peritoneal membrane grows rapidly and soon closes the opening between the pleural and peritoneal cavities. Fig. 42 is from a section lateral to the opening showing the phrenic nerve throughout its greatest extent. In this specimen the marked growth is in the pleural cavity. Fig. 43 is from a section through the opening on a larger scale, including also the adrenal. A stage slightly more advanced is shown in Fig. 44. In this specimen, as in the one above, both pleural cavities communicate with the peritoneal. In Embryo LXXIV, Fig. 4."i, the iileum


FiG. 4.5. — Transverse section through the embryo 14 mm. long. No. LXXIV X 10 times; 7, seventh rib. The plenro-peritoneal membrane ; pp, is incomplete on one side.

peritoneal nienibrane is complete on the right side and incomplete on the left side. The reconstruction of this embryo shows that the opening is very large and extends from the seventh rib towards the tail. It may be an instance of retarded development, because in embryos 19 mm. long the membranes are as a rule complete on both sides of the body. To what extent the permanent diaphragm is formed from the pleuro-peritoneal membrane it is difficult to determine. Undoubtedly the portion of the diaphragm on the caudal and dorsal sides of the pleuro-pericardial membrane is formed from the pleuro-peritoneal membrane. That portion of (lie diaphragm on the cephalic side is formed from the septum transversum. Itut the diaphragm is greatly extended on the lateral sides of the heart after the embr}'o is 20 mm. long by the extension of the pleural cavities around it. It appears from the models that this portion of the diaphragm is also formed directly from the periphery of the septum transversum.


172


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


OBSERVATIONS ON THE PECTORALIS MAJOR MUSCLE IN MAN.

By Warren Harmon Lewis, M. D., Assistant in Anatomy, Johns Hopliiis University.

The Adult Muscle.


The peculiar twist in the sternocostal portion of the pectoralis major muscle is described in the various text-books on human anatomy. In general, the descriptions would indicate that the posterior layer of the tendon of insertion is formed in such a manner that its highest fibres have the lowest origin on the thorax, and the lower the fibres at the insertion the higher their origin on the thorax. There must thus be a crossing of fibres. This crossing is generally represented as


direction of the fibres which form the apparent twisting. For this purpose specimens were taken from the dissecting room, from 1)odies embalmed with the carbolic acid mixture.' The muscles were placed in equal parts of glycerine, water and nitric acid for 24 to -18 hours. In most of the specimens thus treated the direction of the fibres was easily obtained as the connective-tissue elements were partially disintegrated and easily torn.


.— Gq


— h



Fio. 1. — Diagram of an adult peetoralis major muscle, c p, clavicular portion; s <• p, sternocostal portion; 1, 2, 3, 4, 5, 6, are overlapping bundles of fibres of the same ; 6 u, portion of the posterior layer of the tendon of insertion comirg from fi; /i, humeral end of the muscle.


taking place at or near the concave portion of the lower or axillary border of the muscle. I have found many anatomies incorrect or very incomplete in their description of the formation of the posterior layer of the tendon of insertion as well a.s the direction taken by the remaining sternocostal fibres, which go to the anterior layer of the tendon. These descriptions correspond fairly well with the direction the fibres appear to take when one examines the muscle superficially.

I have examined carefully twelve muscles to ascertain the


My dissections have shown in every case, (1) that the lowest fibres of origin go to the lowest end of the posterior layer of the tendon of insertion (Figs. 1 and 2), (2) that there is no crossing of fibres forming this posterior layer, and (3) that a peculiar fan-like arrangeuuMit of the bundles of fibres in the whole sternocostal portion is present (Figs. 1 and 2).

After the maceration, I found the muscle had a tendency

IF. P. Mall, The Preservation of Anatomical Material for Dissection, Anat. Anz., Bd. xi, p- TBO, 1836.


Apeil-Mat-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


173


to split into several overlapping bundles (Figs. 1 and 2; 1, 2, 3, 4, 5, 6). The number aijd size varies in different muscles. It will be seen from the diagram (Figs. 1 and 2) that the overlapping is more and more marked toward the humeral insertion.

The clavicular portion and upper five bundles form the anterior layer, and the sixth bundle the posterior layer, of the tendon of insertion. The lower fibres in each bundle, wliich are the superficial overlapping ones, reach to the lower end of the tendon, while the upper, deeper ones are more and more overlapped and pass to the u]iper edge or near to the upper edge of the tendon. Each bundle, as it approaches the tendon of insertion, spreads out and becomes thinner.


Development.

I have attempted to trace the development of the muscle in a series of human embryos and to explain the origin of the peculiar arrangement of its fibres. For this purpose I have studied the muscle carefully in embryos varying in length from 9 to 40 mm. The first indication of the muscle I have been able to note was in an embryo of 9 mm. in length. In an embryo of 40 mm. the adult form is present. Reconstructions of the younger and dissections of the older embryos were made to study them.

In a human embryo measuring 9 mm. in length (No. CLXIII),^ the pectoralis major and minor muscles are repre



FiG. 2. — Diagram of cross-sections ot tlie muscle talcen at //;, ; 1. ,1, auterior laj'er of tendon ; P, posterior layer.

Tlie distance to which the muscle fibres go outward toward tlie humerus decreases from above downward and thus aids in keeping the distal end of the muscle thin.

The posterior layer of the tendon is continuous with bundle 6 (Figs. 1 and 2). It gradually spreads out and becomes thinner on approaching the luimerus. As in the other bundles, its lower fibres reach the lower and its upper fibres the upper border of the tendon. The size of this bundle varies greatly, especially in the amount of overlapping toward the origin. Most of its fibres constitute the abdominal portion into which the muscle is sometimes divided. The accessory bundles of muscle having, as a rule, costal origin and which lie beneath the main muscle, arc inserted into this posterior layer.


i; op; and rij, in (Fig. 1). Numljers and letters remain as Fig.

sented by a mass of closely packed cells without sharp limits. As there are no muscle fibres in this tissue I shall call it premuscle tissue. The other muscles of the arm and shoulder girdle are also represented more or less clearly by this premuscle tissue. There are, however, muscle fibres in the muscle-plate system. Here the muscle plates have fused into a continuous column and in the costal region extend along the intercostal spaces, partially surrounding the ribs and fuse together beyond their tips into a ventral plate. This muscle-plate system contains fibres, is farther advanced


'The numbers here given correspond with those in the catalogue of the collection of human embryos in the Anatomical Laboratory of the Johus Hopkins University.


174


Johns hopkins hospital bulletin.


[Nos. 121-122-123.


and has a different appearance from the premuscle tissue, which is lateral to it and in the arm. In Fig. 3, which is from a wax reconstruction of the right arm region of this embryo, the costal portion of the mnscle-plate system is seen (m.pl.s). Lateral to this is the lateral premuscle mass {t.pin). At the level of the first rib (cI.) the pectoral premuscle mass ip.pm) leaves the lateral to join the general arm premuscle sheath (a.pm.) along the ventral side of the proximal half of the condensed tissue which represents the humerus. The proximal end of the humerus lies opposite the interval between the fifth and sixth intervertebral disks (dVc, dVIc), the distal end opposite the first rib {cl.). The


tion into masses, such as the pectoral, latissimus dorsi and levator scapulfe and serratus anterior. It is impossible for me in the case of the pectoral mass to determine how far caudally into the lateral premuscle tissiie it extends, or just where to draw the line between it and the neck premuscle mass. Its humeral end is lost in the general arm premuscle tissue. Its location and correspondence with the muscle in the next stage and its nerve supply lead me to believe this to be the pectoral mass.

The pectoral premuscle mass is supplied by three nerves, from the brachial jdexus, the fibres of which come from the 1'/, VII and VIII cervical and I thoracic nerves. It will


apm



Fig. .5.— Ventral view of a wax reconstruction of tbe arm region of a liumaii embryo measuring 9 mm. in lengtli (No. CLXIII). Enlarged TM times. AB, median liiie; c I, c II, <■ HI, -■ IV, ribs one, two, three and iour; d IV <■, (/ V c, d VI c, d VII c, fourtli, fifth, sixth and seventh cervical intervertebral dislis; a. iiiu, premuscle mass eusheathing the arm; I. pin, lateral premuscle mass;

j. pin, pectoral premuscle mass; s. /)»i, scapular premuscle mass.


scapula lies imbedded in the scapular premuscle tissue (s. pm). The clavicle is not present at this stage. The intervertebral disks are of condensed or closely packed cellular tissue {dIVc, etc., to dIVt). The ribs are of condensed tissue and project ventrad from the adjoining parts of the intervertebral disks and vertebral bows.

It is very difficult to determine the exact limits of the premuscle tissue; in a few places it is very sharply marked off from the surrounding mesenchyma as at the ventral end of the neck premuscle mass. The entire arm between the central skeletal core and the integument is filled with this tissue. At the root of the arm there are signs of a separa


be seen at this stage that the pectoral mass is mostly cervical and lies in the region of its nerve supply.

The fibres of the brachial plexus are directed laterally and have scarcely any caudal inclination.

In an embryo measuring 11 mm. in length (No. CTX),' there is great advance in the musculature of the arm. Many of the arm muscles, especially the proximal ones, can be


3 Mall, (F.). The value of Embryological Specimens, Maryland Med. Journal, October 20, 18!)S. A Contribution to the Study of the Pathology of Early Human Embryos. Contributions to the Science of Medicine, dedicated to William H. Welch, Johns Hopkins Hpsi)it«l Reports, vol. ix, I'.IOO.


Apeil-May-Juxe, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


175


recogiiizi'd. Insti'ad uf premusole tissue we liiive distinct fibrillation.

The pectoral nuiscle mass extends from the rejiion lateral to the ends of the first three ribs cephalolateracl to the cephalic border of the humerus. Its cephalic portion is closely associated with the medial end of the clavicle (Figs. 4 and 5, cp.). There is no definite attachment of the mnscle to the ribs. The pectoralis major and minor are closely united. The latter is indicated by a bulging toward the coracoid process {p.min., Figs.. 4 and h). I have with difficulty traced the general course of the fibres in the major portion of the mass, as will be seen in Fig. -5. The fibres from the clavicle do not appear to overlap the sternocostal fibres but occupy the proximal part of the insertion, whih' the sternocostal fibres occupy the distal. See Fig. 6, which is a diagram of the relation of these fibres close to their insertion into the humerus.


It is also worthy -of note tiiat the pectoralis muscle has extended caudally to the level of the tip of the third rib.

In an embryo measuring 16 mm. in length (Xo. XLIII)/ the two pectoral muscles are eutii-ely sejiarate. The pectoralis major muscle assumes much more the adult form than in the previous stage. The entire arm has migrated caudally and with it the pectoralis major mnscle. It now extends to the sixth rib (Fig. 7, cVI.). The clavicle has extended to the tip of the first rib, where it joins the cephalic end of the sternal anlage (si.. Fig. 7). The clavicular portion of the muscles is carried with the clavicle toward the median line. The humeral end of its filjres are seen to overlap the sternocostal fibres near the himrerus (Figs. 7 and 8). There is a distinct gap between the clavicular portion (Fig. 7. cp.) and the sternocostal portion (Fig. 7, scp.) near their origins, The fibres of the sternocostal portion present a slight tendency to separate into bundles in which their is an overlap


lacar



N.Y.C


d.VIC


d.YHC


Fig. i. — .Mediau view of a wax reconstnictiou of tlie arm i-«;;iou of a human embryo measui-iiig- 11 mm. iu leni^th (No. CIX). Eularged 30 times. .1, acromiou; c II, second rib; c, coracoid process; riii\ carpus; ': p, clavicular portion of the pectoralis major; cZ, clavicle; i;h, chorda dorsalis split in the median line; d VI c, d VII t, sixth and seventh cervical intervertebral dislcs ; d I (, first thoracic intervertebral dislc, from which the first rib is seen arising; inrnr, metacarpus; p. m, pectoralis major muscle; p.miu, pectoralis minor bulging toward the i'or.acoid process; n,\ c, fifth cervical nerve going to join the brachial plexus; bp, brachial plexus ; c, radius; id, ulna; .•;, scapula.


Figures 4 and .) are from a wax reconstruction of the right arm region of this embryo. All muscles but the pectorals are omitted.

The ])ectoral muscle mass is supplied by four branches of the i)raehial plexus, two from the outer and two from the inner cord, the fibres of which can be traced to the Vf. VI f andVIII cervical and / thoracic nerves.

It is of special note at this stage, that the larger portion of the muscle lies above the first rib, reaching about to the level of the fifth cervical intervertebral disk; that there is no overlajiping of its fibres; and that the clavicle only reaches about one-half the distance from the acromion to the first rili.


ping of the deep portion of the lower by the superficial portion of the u]iper ones. This is more marked toward the insertion, as will be seen in Fig. 8, where the overlapping is quite complete. I liave not been able to make out at this stage anything which corresponds to the deep or posterior tendon and, as will lie seen later, it probably does not exist at this stage.


' .Mall, (F). Development of the Human Coelom, Jour, of Murpli., vol. xii, No. 2. Development of the Internal Mammary and Deep Epigastric Arteries in Man, Johns Hopkins Hospital Bulletin, Nos. 90-111, 1898. Development of the Ventral Abdominal Walls iu Man, Jour, of Morph., vol. xiv. No. -i, 1S08.


170


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-132-123.


The nerve supply is as in the adult.

Embryo No. XXII,° measuring 20 mm. in length, shows aboiTt the same condition as in Embryo No. XLIII. The separation of the sternocostal portion into various bundles is especially well marked. They have no relation to the ribs so far as the number and position is concerned.



Fig. 5. —Ventral Tiew of a portiou of the model sliowu iu Fig. 4, showing the pectoral muscle mass and its relations to the scapula, clavicle and humerus. A, acromion; c, coracoid process; cl, clavicle; /(, humerus ; p. m, pectoral miiscle mass ; c p, clavicular portiou \ » e p, sternocostal portion; p. min, pectoralis minor bulging; s, scapula.

In an embryo 32 nun. in length (No. C'XXIX)," we find that the j^osterior layer of the tendon of insertion has made its appearance (Fig. 9). The fibres which go to this tendon come from the most caudal portion of the rnuscle. This posterior layer is about one-fourth the width of the anterior layer of the tendon of insertion. The embryo was studied with a dissecting microscope and so far I could determine


?


-C,p

scp.


Fig 6. — Diagram of a cross-section of the pectoralis major fibres near their humeral insertion. Enlarged 50 times. P, proximal end of the same; c p, clavicular fibres; s c p, sternocostal fibres.

the arrangement of its fibres was otherwise similar to the adult.

In an embryo 36 mm. in length (No. XC). we find the posterior layer of the tendon of insertion nearly three-fourths the length of the anterior (Fig. 10). Otherwise the muscle appears to be much as in the adult. The pectoral region was studied with a dissecting microscope.


s Mall, Maryland Medical Jour., October 3'.l, 1S!I,S. Ibid., .Tour. Morph., vol. xiv. No. 3, ISOS. Ibid., Johns Hopkins Hospital Reports, vol. ix, 1900.

"Mall, Contributions to the Science of Medicine, dedieated to William H. Welch, Baltimore, liiOO, Johns Hopkins Hospital Reports, vol. ix, 1900.


In an embryo of 40 mm. in length the posterior layer of the tendon exceeds the anterior in width, and the muscle presents the adult form.



Fig. 7. — Ventral view of the pectoralis major muscle in an embryo measuring 16 mm. iu length (No. XLIII), taken from a wax reconstruction of the arm region of the same. Enlarged 30 times, hi c p, sternocostal portion, various artificial divisions of which a, h, c, cl, are shown near their insertion in Fig. s ; ,■ I, c II, <• V, c VI, euds of first, second, fifth and sixth ribs, which, with the third and fourth join together to form the left half of the pectoralis major muscle; A, humerus, p. m, pectoral muscle mass; scp, sternocostal portion ; s, body of the scapula; M, sternum; c p, clavicular portion; <■;, clavicle"; !i, humerus.

Summary.

It is thus seen that the pectoralis major muscle arises in common with the minor from a premuscle tissue which is



Fig. .s. — Diagram of cross-section of the pectoralis major muscle seen in Fig. 7, near its insertion into the humerus. Enlarged .30 times. P, proximal; ant, ventral surface ; c p, clavicular portion ; a, b, c, approximate position of the corresponding muscle bundles of Fig. 7.

located for the most ]uirt aliove the fir.^t ri1:i. It gradually migrates or sliifts to the costal region, as has already been noted by Dr. Mall.' During the course of this migration it splits into bundles. The clavicnlar portion i.s the fii'st to split off. Later the sternocostal portion splits into the major


■ Mall, Development of the Ventral .Abdominal Walls iu Man. Jour, of Morph., vol. xiv, No. 3, IMIIS.


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


17


and minor. The major becomes arranged into a series of overlapping bundles. As we have seen, the clavicular portion is the upper and most superficial. During the migration the overlapping of the sternocostal Inuidlus is such that superficial fibres of each l.iundle have descended farther than the deeper, owing perhaps to the greater friction of tiie


-a


Fig. 9. — Diagram of tlie insertion of the peetoralis major muscle in an embryo 30 mm. in lengtli (No. CXXIX). Enlarged 16 times. A, anterior layer of the tendon; 6, posterior layer.

latter against the chest wall or to their earlier attachment. The lower bundle seems to be the last to be differentiated, and its tendon, the posterior layer of the tendon of insertion, appears to gradually spread out toward the proximal end of the humerus after the superficial or anterior layer is well formed.

The early entrance of the nerves into the muscle while still in the cervical region explains the adult nerve supply.


Explanation of Varieties. It would seem that in the conditions existing between an embryo of 9 and 11 nun. in length might be found a partial explanation of such varieties as absence of the sternocostal or clavicular portions and of the peetoralis minor with the sternocostal portion. We have here a condition in which


-a


I

Fig. 10 Diagram of the tendon near

its insertion of the peetoralis major muscle of an embryo 36 mm. in length (No. XC). Enlarged 16 times. A, anterior layer; 6, posterior layer.

the clavicle is absent and no attachment to the ribs exists. The subsequent attachment to one or the other might not occur and that portion of the muscle found wanting in the adult. With absence of the sternocostal portion would be associated that of the peetoralis minor owing to their early fusion. In the tendency to split into bundles, with the shifting of the muscle and fibres, the muscular bands which are often found as the costocoraeoidens, sternalis, chondroepitrochlearis, etc., may have their origin.


ON THE BLOOD-VESSELS OF THE HUMAN LYMPHATIC GLAND.


By AV. J. Calvert, M. D., U. S. A., Palhological Laboratory, Board of Health, Manila, P. I.


The lynipliatic glands removed at autopsy from pest cadavers have enabled me, on account of the extreme congestion incidental to the disease and the reduction in the density of the nuclear elements of the gland, to follow in detail the course of the smaller vessels; the pathological changes referred to are not of sufficient degree to destroy the landmarks of the organ or to change the general relationship of the parts.

In an earlier communication I showed the course of the blood-vessels in the lymph follicle in the dog, and the present report is made because it demonstrates that the same arrangement is present in the human lymphatic gland.

The glands were fixed in Zenker's fluid, hardened in alcohol, sectioned in celloidin, stained in hematoxylin and eosin and mounted in balsam.

The illustrations show the origin and distril)ution of the follicular artery, the arrangement of the capillaries in the follicle and the origin of the veins. The course of the


arteria; and vena; lympho-glandulae and the vessels of the cord have been illustrated.'

From the above illustrations and the many typical pictures seen in the slides the following scheme for the blood supply of the human lymphatic gland may be described: The arteri* lympho-glandulffl enter the gland at the hilus, pass through the hilus stroma to enter the trabecule. In the trabeculae arterial twigs are distributed to all portions of the gland. On reaching the portions of the gland near the proximal ends of the follicles small arteries arise which run in the lymphatic structure more or less parallel to the surface of the gland. These arteries give rise to the follicular artery (Figs. 1 and 2) and supply the adjacent portions of the pulp cords.

The follicular artery runs a straight course in or near


> The Blood-vessels of the Lymphatic Gland. By W. J. Calvert Anatomiscber Anzeiger, xiii. Band, Mr. 6, 1897, p. 176.


178


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


the centre of the ]yiii]ih cord of its particiihir follicle, to ahont the junction of I lie jiroximal with the middle third of the follicle. The ftillicular artery may give off branches to .«u])])ly the adjacent jmrtions of the cords. Near the centre of the follicle the artery breaks np into a number of small, straight, long capillaries which diverge to the periphery of the fdllicle. In some cases these capillaries branch, in others they do not.

Just beneath the periphery of the follicle these capillaries turn and branching form a rich plexus of capillaries wdiich in turn unite to form small veins (Fig. 6). The ])Iexus of capillaries in the follicle is continuous with a similar plexus in the cords.

The veins formed in the follicle run toward the jjroximal end of the follicle to join a rich plexus of veins.

The arteries supplying the cords are, as a rule, quite short.


run in or near the centre of the cords and rapidly end in a rich capillary plexus near the surface of the cord. This plexus soon unites to form snudl veins which also run in or near the centre of the cords, but in a |iortion of the cord other than where the artery is found. The veins of the cord soon join veins from neighboring cords, through the anastomosis of the cords, to form larger veins which leave the cords to join the vensE lymjilio-glauduliP.

The veins from the follicles and adjacent jiortions of the cords unite to form a rich venous plexus, which lies within the lymphatic structure. This ])lexus may bo considered to be the origin of the ven;B lymjiho-glandula', which, like the arteries, run in the trabecula? to leave the gland at the hilus.

The lymph channels are free from blood-vessels.

This arrangement of blood-vessels is also found in the lymph gland of the monkey.


NORMAL MENSTRUATION AND SOME OF THE FACTORS MODIFYING IT.

(PRELIMINARY NOTE.)

By Cleli.v Duel Moshee, A. LL, M. D.,

Gi/nwcolor/iral E.rlcrne in the Johns Uopl'ins Ilospital Difiiciisarij.


The conclusions stated in this note are liascd on two kinds of data — clinical and experimental. The first consists of serial menstrual records of more than 300 women, collectively extending over more than 3000 nienstnud periods. A large number of these records were made by the writer, month by month, when the women Avere under her personal observation in the Stanford University Gymnasium, and then were continued by the women themselves during holidays and vacations away from the university. The records were supplemented by preliminary statements, careful intermenstrual notes, and subsequent letters. The usual physical examination for admission to the gymnasium was made by the writer in many cases; to this was added an intimate knowledge of the conditions under which the women were living and working. Second. laTioralory experimental data on the i-es])ii-alioii,' urine, tcm])erature, pulse and l)lood — blood |)ressure, blood counts, hemoglobin estimations and so on. Experimental work on the effects of clothing was also included. This work luis been done in the physiological laboratories of the Stanford and the Johns Hopkins Universities, and in Dr. Kelly's laboratory. The first work was done in May, 1893, in California, has been continued as o|i|iortunity offered and is still in progi'css.

Some of the more important conclusions, which are based largely on the blood-jiressure experiments and clinical data will be reported at this time.


• "Respiration in Women," Preliminary report as thesis for M. A. degree, Stanford University, May, 1.S94. Also paper presented at California Science Association, .Ian. 3, IS',16.


McthuiL — Daily records of the blood pressure were made on 14 persons— woincn and .'J men. The \vomen were selected as representing normal conditions of menstrual health. The iiK'U were all healthy adults and 4 were athletic, ^n attempt was made to continue the records long enough to cover at least two periods of change in pressure; in some cases the observafions extended over 49 days and some are still in progress. The blood-pressure records were made with the sphygmomanometer of Mosso. The tracings were taken daily at the same hour and under uniform conditions, perfect rela.xation being secured and all varialile factors excluded as far as possible.

Conchisions. — That a rhythmical fall of bl(jod pressure, at definite intervals, occurs in iKith men and women. The daily records of the blood-pressure with the sphygmomanometer of Mosso on men and women inider similar conditions of life and occu|)ation give curves apparently indistinguisliahle in chai'acter. The fall in pressure in women occurs near or at the menstrual period. In all of the 14 series of records the fall of blood-pressure was gradual from the mean average pressure. This from day to day shows oscillations .within rather definite limits. The maximum fall of ]iressure may extend over two or three days and the coi-responding rise to the normal average jn'ossure is gradual. There is usually a jireliminary rise, above the normal average jiressure; this occurs from 3 to 5 days before the onset of the main fall of pressure, wdiich constitutes the principal feature of the rhythm. Tn every case there was a preliminary fall, abrupt and definite, but usually not so extensive as the main fall of pressure; this preliminary fall was followed by


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXXi


Fig. 1.— The follicular artery and its capillaries. One of the long capillaries is seen to join a venous capillary in the periphery of the follicle; on either side of the follicle small veins are seen. Transverse sections of several veins are also seen.

Measurements: artery before dividing. 41 microns; and capillaries from 8 to 10 microns iu diameter


^«^« 



^-'ny^'^f^f


(^rr,




Fig. 2. — The origin, course aud distribution of a long follicular artery.

Measurements: at origin, o4 microns; and before dividing, 31 microns; capillaries in follicle, from 7 to 8 microns.


^5gft-.




■~^&




■A:


Fig. .5.— Two follicular artery an artery is seen end of the follic


follicles with their veins. The follicle on the right shows a portion of a entering the centre of the follicle. Below the proximal end of the follicle running parallel to the surface of the gland to turn toward the proximal

le ; here it is lost.


Fig. 3. — An artery arising some distance below the proximal end of a follicle, running toward the follicle to turn at a right angle aud run to the centre of the proximal end of the follicle; here it again turns at a right angle to enter the follicle, where it divides iu the usual manner.


^S??Sf^?SQ3:?'SWfS9i%.


%^'




$



l«^


Fro. 4. — A double arterial siipjily to the follicle.


Fig. 6. Long curved capillaries, c, near the periphery of the follicle.


Apbil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


179


a return to tlie iiimiuil or hijrhcr })ressurc' Ijet'ore the iiriiieipal i'all oeeiirred. In 4 cases tliere was a distiiiet rise above normal after the main fall of pressure before the return to the normal daily oseillations. These variations were not peculiar to either sex.

A curve constructed on tlie subjective observations of the sense of well lieini;'. shows ups and downs eorrespondiiii;' to the marked vai'iations in pressure; the sense of maximum efficiency of tlu' individual corresponding to the time when the pressure is hii;]i. and lessened efficiency to the ]ieriods of low pressure. Tiie observations were carried on iiulopendently of each other. In no case was the change sufficient to incapacitate the indixidual. The time of low pressure appears to l)e, in Loth sexes, a jjeriod of increased susce]iti])ility. If symptoms of any kind are shown they are apt to he given by the point of least resistance. For exauqile, if a man oi' woman having a tendency to digestive disturbances, the symptoms from the digestive tract are likely to occur at the jjcriod of l(]\v blood pressure: or when a slight chronic catarrh exists, as so fre(|uently ha])pens in this climate, there may be marked increa-e of symptoms from the resjiiratory tract.

In Women the fall in blood jiressure most frecpiently occurs before the menstrual How. the maximum fall being coincident witli the onset of the flow; there is a gradual ret^irn to tlie lujrmal mean pressure by the time the menstruation ceases. Occasionally llie fall oecui-red during the flr.w.

Wliile true dysmenorrlnea is far too fretpicnf. much of the so-called menstrual sutfering is not dysmenorrhcea but simply coincident functional disturbances in other organs, induced, l)ossibly, by 'the favoring conditions of a lowered general lilood pressure occurring near or at the time of menstruation, ((.ioodman's restricted definition of menstruation is adhered to — ^" A periodic sanguineous defluxion from the genital tract.")

When tile attention is of necessity directed to so obvious a


l)rocess as the menstrual flow, untrained women, especially if without absorbing occujiation, naturally refer their lessened sense of w'ell being and diminished sense of efficiency, which may accompany the lowered general blood pressure occurring near or at the menstrual flow, to the fnnctiou of nu'iistruation. When we remendier how firmly fixed is the tradition that a woman nuist sufl'er and be incapacitated by this normal physiological function, it is .readily understood how many women would call the depression due to lowered blood pressure, menstrual suffering.

All statistics, however extensive or carefully taken, arc likely to exaggerate the percentage of women suffering fi'om dysmenorrhcea, because the errors just mentioned are so difficult to eliminate.

The conception that functional disturbances in other organs are considered and recorded as dysmenorrhcea was first derived from the study of the clinical data and later strengthened by the blood-iiressure experiments supplemented by tlie notes of the ]ier,sons studied.

The conclusions of this paper would have been impossil)le had my clinical data consisted merely of isolated statements ba.sed on the general impressions, as to their own conditions, of individual women filling out a single menstrual record, and without a personal acquaintance with, and an intimate knowledge of, the haliits of life and conditions of work of the women studied.

Although S]iace forbids detailed acknowledgements at this time, I wish to state my obligations for many favors received at Stanford University in the earlier work; to Dr. Howell and his associates, Dr. Dawson and Dr. Krlanger of the Pliysiological Department of the Johns IIoi)kins ITniversity; to Dr. Kelly's lilierality and generous encouragement which have made possible all of the later work. The intelligent cooperation of my former students and many friends and of the nu'U and wcunen who have recently given and are giving so much of their valuable time, has made this work possible.


RETROJECTION OF IIILK INTO TIIK I'AXCKEAS, A CAUSE OF ACUTE IIEM01II!11A(IIC

FANCREATITIS.


I;v W. S. II.\L8TED, M. D.


Mr. T., aged 18, a cor|julenl and robust looking man, Jiad been subject to attacks of " indigestion," attended with pain in tlie epigastrium and a feeling of distention, for several years. These attacks would .sometimes incajiacitate him for business, lie had a severe attack of this kind la-st Christmastide. He described also attacks of "vertigo," which had laid him U]) for S or 10 days every spring, with perha]is one exception, for the past ten years. At the end of April, 1901, be arrived in Baltimore after a hard railr(ia<l trip of about S days. On the way, suffering with indigestion, he bought a two-ounce package of bicarbonate of soda, half of wbieb lie consumeil. After Inneheon on the dav of liis arrival he


was seize<l (piite suddc^nly with a severe pain in the abdomen; he was nauseated and expressed his desire to be relieved of the "gas in the stomach." His physician administered calomel, and later nux vomica and carminatives. For 2-1: liours he was relieved; then, -after eating buckwheat cakes, the pain returned. Occasionally driiddng large quantities ■^of water, he forced himself with difficulty to vomit. He suffered almost constantly more or less pain for a week, Init took his meals regularly and slept about as well as usual. About noon on the Htb of May, the pain became very severe; morphia administered hypodermically three times during the afternoon. J grain in all, did not give much relief.


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Inhalations of chloroform had to be given. At 9 j). ni. I was asked to sec him by his attending i)li3'sicians. As I entered liis bedroom, lie was walking al)out in his pajamas, excited and iiervous, and his teeth chattei'ing; he seemed to be in great pain. His pulse was full and regular, 92 tlie first count and 87 the second. When I attempted to examine him he made an effort to keep quiet but in a moment had to spring up again. He was sensitive to pressure over the epigastrium, but not exquisitely, the point of greatest tenderness being a little above and, I thought, to the right of the umbilicus. He was "somewhat cyanosed. My attention was called to the cyanosis by the print of my fingers on his abdominal wall. His condition was so good tliat I tliought, with his physicians, he was jirobably suffering from gall stones. He refused to go to tlie hospital. Hot baths during the night relieved him, I am told, for the time, but he had to be chloroformed frequently. In the morning he was anxious to go to the hospital and was operated upon immediately after his arrival, about 11 a. m.

Operation. — The cyanosis of the patient was much more striking as he was laid on the ojierating table, and lie vomited as he was being antesthetized. The abdomen was not distended, but the panniculus was very deep. On opening the belly through the middle line blood-stained fluid escaped and at once it was noticed that the omentum showed abundant fat necroses; these necroses were to be seen in the subperitoneal fat, in the mesentery, along the lesser and greater curvatures of tlie stomach, etc. In order to explore more fully the pancreas and to make sure that a certain hemorrhage in the wall of the stomach, near the pyloric end, had not produced any serious lesion, the omental bursa was rapidly opened. Nothing that could be designated as a tumor mass was made out; the entire region of the pancreas could be palpated. The tissues over the pancreas were slightly infiltrated with blood-stained scrum. The common bile duct, however, was distended to the size, perhaps, of an index finger. The presence of a stone in the diverticulum was of course suspected, and a careful though luirried search made, but none could bo felt; the fluid in the abdominal cavity was rapidly sponged out and a gauze pack placed over th(' head of the pancreas. The abdomen was then closed. The patient died within 23 hours.

Pain, vomiting, distention of the abdoiiien, sometimes an clastic swelling in the region of the pancreas, fluid in the peritoneal cavity, pulse 140 to IGO or higher, cyanosis, collapse -tliese arc the symptoms which the surgeon calls to mind when he pictures to himself a case of acute hemorrhagic pancreatitis, and hence it is that this disease has so many times been considered acute intestinal obstruction. My patient was strong, restless and walking about the room, not collapsed; his pulse was 92 the first count, 87 the second; the abdomen was not only not distended but. according to the patient, had greatly diminished in size during the few weeks preceding this illness; the reduction in the size of his waist, as evidenced by the considerable space between the band of his trowsers pnd his abdominal wall, was a matter


which ajiparcntly gave him some concern, for he referred to it more than once. Vumiting, it' present, was so inconspicuous a .symptom that it had not been noticed; the ]jatieiit had perluqis 3 or -1 times tickled his pharynx because he tluiught it relieved him to gag and bring up a little mucus from his stomach. When I saw him about 13 hours before the o])eration and again an hour before it, pain in the epigastrium and slight cyanosis were his only symptoms. But the pain must have been intense and seemed greater than I had ever seen it in cases of gall stone. I had the misgiving that I was in the presence of an unfamiliar affection and was prepared for a surprise when I opened the abdomen; and yet acute pancreatitis did not occur to me, my conception of the clinical picture was so different. But I shall not soon forget this case; the excruciating pain in the epigastrium and the cyanosis; altogether, a clinical picture difEerent from anything that I could recall. To save my colleagues and students the humiliation of making the same mistake, I have thought that it might be well to represent graphically the only sign which this obseurc case ])resented, the white print of fingertips in a slightly cyanosed field just over the site of greatest pain. Attacks of acute hemorrhagic pancreatitis, mild and severe, are probably much more common than is generally supposed, and I am sure that the clinical picture is sufficiently definite to be easily recognized by the general practitioner.

The autopsy was most carefully made by Dr. Opie, whose description of it will follow. The .stone, which I could not find in my hurried search at the operation, was almost too minute to have been detected under the circumstances, and even at the autojisy it was only after prolonged handling and probing of the papilla itself outside of the body that the presence of a stone was determined. Opie has found that gall stones have been present in the majority of the more recently reported cases of acute hemorrhagic pancreatitis. In some instances they were, imdoubtedly, not carefully searched for, in a few they may have been overlooked and in others they may have passed the papilla, having been arrested in the diverticulum long enough to produce the lesion in the pancreas. If it is true, as this case and Opie's experiments recorded below prove almost beyond question, that acute hemorrhngic j^ancrcatitis may be caused by liile retrojected into the pancreatic duct, the inference that milder lesions and subacute and chronic changes may be produced in the pancreas by the mere presence of bile in its ducts is natural. The fact that the entire pancreas is not always or even usually involved, normal areas being found here and there among the hemorrhagic ones, makes it seem not unlikely that quite small patches may at times be afEected and that the symptoms after very limited involvement might be overlooked or misinterpreted. Epigastric pain, rapid pulse, nausea, vomiting and possibly hematemesis coming on either soon or long after operations upon the common duct might in some instances be attributable to lesions in the pancreas.

The Mechanism, — The arrangement of the parts concerned


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in the production of acute hemorrhagic pancreatitis reminds me of the liydraulic ram in its primitive form. The ductus clioledochus is the feed pipe, tlie pancreatic duct tlie delivery pipe and the calculus the ball valve or stop cock. Although I know of no experiment to determine the force with which bile may be ejected from the gall bladder, it is conceivable that the sudden and complete interruption of the flow of bile during digestion by a calculus might give rise to a retrojection spurt of considerable volume and velocity. But whether this force is considerable or not, since the pancreatic juice and the bile are secreted at almost the same, quite low (3j^ini. of water) pressure, it would probably be suflicieiit, as Dr. Opie will show, to drive the bile into the pancreatic duct under the proper conditions.

Why is pancreatitis hemorrhagica acuta such a rare disease?

1. That bile may be retrojeeted into the pancreatic duct, the stone must be (a) too small to occlude the pancreatic duct or interfei'e with the force of the jet aud at the same time (6) too large to pass the papilla.

2. A narrow papillary orifice, such as we found in my case (a rare condition), would predispose to this affection, because many stones small enough to fulfill (a) the first condition are too small to fulfill (b) the second.

3. One calculus would be more likely to cause the pancreatitis than several, for other stones in this duct, unless very small, would weaken the force of the bile-spurt which drives the ball valve against the papillary orifice. I have elsewhere called attention to this fact.'

4. The gall bladder must perhaps be normal or nearly so; not thickened, shrunken or weakened by inflammation. Accordingly, one must have a calculus or calculi which have produced insignificant changes, if any, in the walls of the bladder.

5. The anomalies which Dr. Opie will consider protect a certain proportion of cases.

6. A predisposition may be necessary, as is given by adiposis and excessive use of alcohol.

Apropos of what I have said as to the possibility of mild attacks of hemorrhagic pancreatitis after gall stone operations. Dr. Finney has just told me the story of a most interesting and perhaps not wholly unique case. Four months ago he did a choledochotomy for 2 large soft stones in the common duct. The duct was enormously dilated, the gall bladder atrophied. The stones were almost as mushy as damp salt, and crumbled to pieces in the duct. The detritus was removed with extreme care and the duct afterwards repeatedly flushed with the physiological solution; notwithstanding this it seemed to Dr. Finney that some grains still remained in the duct. The incision into the common duct was sutured and the convalescence was entirely uneventful except for a trivial leakage of bile beginning about the 7th day p. o. A few days ago, when in robust health, the patient was seized with excruciating pains in the


' Halsted. Contributions to tlie Surgery of tl\e Bile Passages. Tlie Johns Hopkins Hospital Bulletin, .January, 1900.


epigastrium, unlike any that he had ever experienced. Dr. Fiuney was telegraphed for promptly and reaching the patient in a few hours found him vomiting, collapsed, cyanosed and suffering pain so severe that morphia in large doses did not control it; tb.e pulse was aliout 160, pressure over the pancreas was unendurable, the abdomen was distended. Acute pancreatitis was suspected, and operation, considering the collapsed condition of the jiatient, deemed inadvisable. The following day the patient was brought to the Johns Hopkins Hospital, his condition was greatly improved and 48 lioui's later he seemed perfectly well.

Is it not probable that in this case one of the fragments increased in size may have been responsible for the attack? Was the fragment passed? What were the lesions in this attack ? Acute pancreatitis just beginning to be understood will probably soon become a household word.

Trealmeni. — We must learn to make the diagnosis pronijith-, and to distinguish gall stone attacks per se from those attended with pancreatic complications.

To search for and remove the stone in the diverticulum as soon as possible after the appearance of the first symptoms would be the correct procedure in some cases if the true nature of the attack could be recognized early enough. If this patient of mine had been operated upon and the stone removed at some time prior to the onset of his severe symptoms, perhaps at any time within the first seven or eight days of his illness, it seems probable that his life could have been saved. Without operation there was little if any hope for him, for the conditions responsible for the lesions would have persisted. It was evident at the operation that the common duct was obstructed but the patient's condition absolutely eontraindicated prolonged search for the cause, which probably could only have been determined by opening the common duct or the duodenum, so minute was the calculus. Operation should not be undertaken upon cases in collapse, but the bloody fluid, probably highly toxic,' may he hastily evacuated by laparotomy (local anaesthesia) in cases too ill for radical operation.

Of 25 cases of acute hemorrhagic pancreatitis operated upon only two have recovered,' a case operated upon by me eleven years ago" and Hahn's case recently reported.*

In his recent article Prof. Hahn expresses a desire to learn if the operation performed by me in the case which recovered was prolonged by the usual search for some cause of intestinal obstruction, and the hope that, in future, inoculations of culture media will be made from the blood-stained abdominal fluid. It gives me pleasure to be able to reply and to state that fat necrosis was at once observed, the diagnosis promptly made and the operation, therefore, probably a short one: drainage was not employed. This patient is alive and apparently well. In the second case, inocula


sHahn. Deutsche Zeitsehr. f. Chir. Brt. 8.5. Heft 1. 3 Kortc. Die Chirurgisehen Krankheiten unci die Verletzungen des Pankreas.

Hahn, 1. c.


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tious from the bloody abdomimil Ihiid wore made, aud witli negative results.

It seems not improbable that, as Hahii states, the rapid evacuation ol' the bloody tluid in the abdominal cavity may in some cases be benelicial. llahu believes that this fluid is highly toxic and perhaps inlectious, and emphasizes the fact, e.\emplified by one of the cases which he reports, that large retroperitoneal extravasations of blood cause incomparably less disturliaiice than we see in these cases ol' hemorrhagic pancreatitis in which the loss of blood is insigiiilicant. I had read llalurs article only a few days prior to the o])eration upon tliis case and was acting u[ion his suggestion, but coming so quickly upon the dilated common duct 1 lelt myself compelled to make a hurried scari'h for the cause of the obstruction. I have little doul)t that my operation hasteiu'd the death of the [latient.

If a stone in Venter's diverticulum was the cause of the pancreatitis in my first case, the one that recovered after oj)eiatiiin, we must conclude that it passed the |ia)iillii, prolialily dnring the attack, for it had [u-oduced no symptoms fronr the time of the operation, May. 1890, until June, 189."), when he was examined in the hospital by Dr. F)loodgood. I fiml that I misinformed Dr. Korte' when I wrote hiui that my recovered case had had a subsequent attack. The attack referred to oecu"]i'e(l in aiiotlier case, one of suppui-ative pancreatitis, operated upon and cuied by my associate. Dr. I""inney.

Kitrti* ; Die Cliifu ri;is(!lii-'ii Ki':tnkliriti*n iiiid die \'t*ii('1zniii:"i-ii dcs ?:iulirciis. Deutselii- Cliir. IS'.IS, ji. 171.


TTTE ETIOLOGY OF ACUTE HEi\IOKRTIAGIC PANCKKATITJS.

JjY Eugene L. Orn:, M. D. fiislruf/iir ill Paihologij, Johns IlopMn.i Uiiiirrsilji.

(Fi-inii III, l;il/i„lv,/ir,i/ Liihiiiiitfiri/ of l/ii .h.hiis lli'iikuis C.iiviKil,/ ,n,d J[..s,nl.,l.)

Pathological Eepoht.

In many reported cases of hemorrhagic and of gangrenous pancreatitis symptoms of cholelithiasis have been associated with the fatal illness and at autopsy calculi have been found in the gall bladder or in the bile jjassagos. In a recent article ' I collected from the literature thirty-one cases of this character and described an additional instance. In eight of these cases, including the one which I reported, a gall stone was found at autopsy lodged near the orifice of the common bile duct or there was evidence that one had shortly before death occupied this position. Since the common bile duct and the duct of Wirsung unite to form the diverticulum of Vater before they enter the intestine, a calculus so located might occlude both ducts. In the greater number of these collected cases though calculi were found at autopsy, none


' Opie. Amci'. Jmir. of tlie Med. Se


I'.Kll,


exxi. [1.


were situated near the junction of the two duets. Nevertheless since, as was pointed out, death with intense hemorrhagic inflammation of the gland has in several instances followed within forty-eight hours the onset of symptoms and a ealeulus has been found near the duodenal orifice of the eommiin duet, it is readily conceivable that a stone tein|)oi'arily lodged in the position indicated might produce grave alteration of the gland before its final expulsion into tlie duodenum. In seven of the thirty-one cases death followed the onset of symptoms, intense abdominal [)ain, vomiting and profound coflapse, within forty-eight hours, and at autopsy the jiancreas was the seat of hemorrhagic infiltration. In seventeen instances in which tlu' fatal illness was of longer duration, seven days to four months, the paiu-reas was gangrenous and there was often evidence of pi'evious hemorrliage. There can be little doubt that gangrencuis p;ini-r('atitis is a late stage of the hemorrhagic lesion.

That acute pancreatic disease is fre<pieiitly iissociaied with ebolelilhiasis has been conliiined by cases ie[iorted since the preparation of the article referred to. The two conditions were |)resent in three cases recently described by Lund," in two by Bryant' and in one by Stockt(Ui and Williams,' by Struppler ' and by Ilahn. The relative frequency with which acute pancreatitis is accompanied by cholelithiasis is dillicult to estimate. In some cases the lesion has been tbagiiosed upon the operating table and, no autopsy being obtained, the condition of the bile jiassages has not been determined. In a very large proportion of the cases the nntojisy report is so meagre that the presence or aljsence of gall stones is not evident. Lund records the relatively large number of six cases of acute pancreatitis, one siqipnrafive, five hemorrhagic or. hemorrhagic and gangrenous. Two of the five cases he describes as hemorrhagic peripancreatitis. ill three of these live cases the gall bladder or the bile passages contained small calculi in large number, wliile in the remaining two no autopsy was obtained. In the two cases reported by liryiint hemorrbngic pancreatitis was associated with gail stones. In only one of the five cases of Ilahn were gall stones present, but in one of his cases hemorrhagic infiltration of the gland followed a pistof shot wound and in another recovery followed operation, (lall stones were, therefore, present in six of eight cases with autopsy described by three writers who have recently reported more than one instance of the disease.

In view of the fact that in several instances a calculus has been found at autoj)sy so lodged as to occlude the jianereatic duct, there can be no douljt that the frequent association of the two conditions is the result of an etiological relationship. The common liile duct and the larger pancreatic duet lie side by side as they penetrate the wall of the duodenum and are often separated near their junction only by a thin mem


'I^iiiid. Boston Med. and Surg. Jour., 1!>00, exliii, p. M?y.

' Hrynut. Liinoet, IflOO, ii, p. lo41.

■•Stoclcton .ind Williams. Philadelpliia Med. .Tour., I'.lOd, vi, p. (;4!l.

'•Struppler. Dcutsehe Arcli. f. Ulin Med., liieo, Ixix, p. JOC.

«Hahn. Deutsche Zcitschr. f. Cliir., Umo, Iviii, p. 1.


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branous septum, while before entering the duodennm at the suiumit of the bile papilla they unite to form a short channel, the diverticulum of Vater. From a study of the case previously reported it seemed not improbable that a calculus lodged in the common bile duet near its termination might cause partial occlusion of the pancreatic duct and subsequent changes in the pancreas as the result, possibly, ol' bacterial invasion. This case, as well as those recorded in the literature, alforded, however, no explanatirm of the pathogenesis of hemorrhagic inflammation. Tlie autopsy recently performed upon the case described Ijy Dr. Halsted has dciiionslruted a mechanism by which this lesion is produced.

Aulopsij. — The body, which is still warm, is tliat id' a large man with very abundant subcutaneous fat. The skin has a bluish cyanotic appeiU'ance. Passing downward from the right costal margin to a point 10 cm. from the symphysis pubis is a longitudinal incision, closed in great part by subcutaneous silver wire sutures. Crossing tiie epigastric region and meeiiug the hrst at right angles is a second incision. At their angle of junction the wound is unclosed for a short distance aiul gauze packed aboid by rubln'i- protective passes into the abdonunal cavity.

The jiei'itoneal cavity contains a moderate excess of l)ioodstained serous lluid. The general peritoneal surface is smooth. l<'at is present in very great amount in tlie omentum, in rnml (it the peritoneum of the ant<i-i(ir alidoniinal wall below tlie umbilicus, in the mesentery, in the retroperit(}neal tissue and as appendices epiploic^ upon the surface ol the large intestine. Studding the fat in the various situations named and conspicuous upon its translucent surface are small usually round opaque white, areas 2 to 3 mm. ^n diameter, often surrounded by a narrow zone of injection: They ai-e sujjerficially situated and extend usually less than 1 mm. below the surface. They are most abundant in the omentum and in the retroperitoneal fat adjacent to the pancreas. The gauze drain previously mentioned passes between the stomach and the transverse colon and lies in contact with the retroperitoneal fat immediately below the head of the pancreas. Here tlie tissue has a reddish-black discoloration.

The pancreas is represented by a blackish sw(dleu mass extending from the descending part of the duodenum to the spleen. The fat in contact with its splenic end has a similar blackish color and is soft and friable. The pancreas is greatly increased in size, is irregularly cylindrical in shape and measures 5.2 cm. antero-posteriorly, 5.5 em. from above down, and 16 cm. in length. The anterior surface is smooth and has an almost uniform black color in places with a reddish tint. On section the gland substance is found to be in great part transformed into black and reddish-black material. The head of the organ for a distance of 2.5 em. from the duodenum is firm, gray yellow, with well marked lobulation, and has the appearance of the fresh normal pancreas. Tissue « hicli is in immediate contact with this well preserved gland substance is soft and black in color, mottled here and there with small areas of dull red; gland lobulation is still very


obscurely marked. The distal half of the organ shows a similar mottling of black and reddish areas with in places small islands of yellowish, relatively preserved tissue. The largest of these, which is of reddish-yellow color, gradually passing into the surrounding reddish-black, is 1.5 cm. in diameter and is situated near the middle of the body. At the splenic extremity is a slightly smaller mass of intact gland substance. On opening the splenic vein where it lies in contact with the jiancreas the intima is found to lia\( a mollled yellow, blackish and red appearance, due to cbanges iu the underlying tissue. Occupying a portion of the lumen is a mixed red and yellow thrombus mass, fifin in consistence and adherent to the intima.

The duodenum was opened and the common orifice ol' tlir bile and pancreatic ducts examined. The papilla is prominent but its orifice is of small size measuring 1 mm. in diameter. The common bile duet which near its termination is completely embedded in the substance of the pancreas is slightly distended. By very firm pressure on the gall Idadder .-everal drops of liile can be squeezed with dithculty into the duodenum. The gall bladder when opened is found to eontain a moderate amount of viscid blackish bile; no concretions are present. The termination of the pancreatic duct, which is surrounded by the well preserved pancreatic substance in contact with the duodenum, was exposed by dissection and found to unite with the common bile duct 10 mm. from the summit of the bile papilla. A probe passed dow^n the common duct was stopped -1 mm. from the latter point, and it was not possible to touch it with a second probe passed into the narrow orifice. Careful examination disclosed a small graywhite, very firm concretion 3 mm. in diameter, snugly filling the diverticulum of Vater from which it could not escape through the narrow duodenal orifice. The pancreatic duct, where it passes through the intact tissue of the head, is like the common duct stained firight green with bile.

The heart and lungs are -apparently normal. The liver weighs 1350 grins. The surface is smooth and of yellowish color; upon the upper surface of the right lobe are conspicuous slightly depressed dull red areas which are irregular in ■ shape, the larger about 2.5 em. across. The cut surface of the organ has a bright yellow color, the periphery of the lobules being golden-yellow, the central part reddish. Corresponding to the superficial red areas the liver substance has a similar dull red appearance, the periphery of the lobules being marked by narrow yellow zones. Such altered tissue has at times an irregularly wedge-shaped outline and within it are found portal veins distended and plugged with red thrombus material. Following the vein in one of these areas toward the main portal trunk, the thrombus stops abruptly and near its end is of yellowish-white color, representing probably embolic material from the thrombosed splenic vein. The spleen is not enlarged and weighs 140 grms. The organ is flaccid but fairly firm in consistence.

The stomach contains a small amount of blackish semifluid material. The duodennm and remainder of the small intestine contain similar material. The kidneys, weighing


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together 290 grms., appear to be normal, except for the presence of opaque yellow striations near the apices of the pyramids. The adrenals, the bladder, the seminal vesicles and the prostate are normal. Upon the intima of the aorta are a few slightly raised opaqiie yellow patches of small size. The urine contained in the bladder does not reduce Fehling's solution.

Microscopic examination of the pancreas. — A section passing through tlie line of demarcation between the intact parenchyma in the head of the gland and the adjacent necrotic tissue shows a very abrupt transition from the one to the other. On the one side the pancreatic tissue is well preserved, the secreting cells are normal in appearance and their basal zone stains deeply with haimatoxylin, while islands of Langerhans are fairly abundant and appear to be normal. The loose interlobular areolar tissue is everywhere infiltrated with red-blood corpuscles; polynuclear leucocytes are present in large number and often form collections of considerable extent. Eosinophilic leucocytes are numerous and fibrin is abundant. Between the acini are a few polynuclear leucocytes. Within the margin of the intact tissue are several small areas where the parenchyma is undergoing necrosis. The secreting cells no longer stain with hfematoxylin, but assume a homogeneous clear pink color with eosin; the nuclei which are still preserved are much smaller than those of the normal cells and unlike the latter are irregular and distorted and stain homogeneously. Small hemorrhages have taken place into the interacinar tissue of such an area, and polynuclear leucocytes are present in moderate number. Nearby in similarly localized areas the process is more advanced and the parenchymatous cells are replaced by formless material which staining faintly is mingled with a few nuclear fragments and is densely infiltrated with polynuclear leucocytes and red-blood corpuscles.

The transition from relatively normal parenchyma containing a few islands of necrosis to wholly necrotic tissue is very abrupt and is marked by a zone composed of nuclear fragments, polynuclear leucocytes, red-blood corpuscles and fibrin. That part of the section which corresponds to the black and reddish-black material seen macroscopically is necrotic, nuclei are no longer present and though the architecture of the gland is still obscurely definable both parenchyma and connective tissue stain only with eosin. At intervals in areas of varying extent the tissue has a dark brown discoloration due to the presence of brown pigmented material which appears to be changed blood.

Sections from the body and tail of the organ present the appearance described above. In the intact tissue of the tail well preserved islands of Langerhans are particularly numerous. In a section from the body nuclei still persist immediately about an artery, though the surrounding tissue is universally necrotic. Its endothelial cells are swollen and in places are almost cubical. In the media and adventitia, of which the vasa vasorum are preserved, polyaiuclear leucocytes are very numerous.

In sections stained by Weigert's method for the demon


stration of fibrin was noted a histological detail inconspicuous by other methods. Capillary vessels in the living tissue near the margin of necrosis as well as in the immediately adjacent necrotic part liave undergone hyaline thrombosis and form conspicuous deep blue, often branched, lines as though injected. Examination with high magnification demonstrates at times a close meshwork of fibrils in these vessels. In sections stained with hannatoxylin and eosin their contents take a homogeneous briglit pinkish-red stain and red-blood corpuscles are no longer seen, as in adjacent capillaries.

lu sections stained for bacteria with niethylene-blue, with gentian violet, and by Weigert's method, none were discovered.

Bacteriological e.vamination. — Plate cultures in agar-agar were made at autopsy from the heart's blood, peritoneal cavity, pancreas (aerobic and anaerobic on hydrocele agaragar), gall bladder, liver, spleen, and kidney. They were studied by Mr. V. II. Bassett to whom I am indebted for the following report. Cultures from the heart's blood, spleen, and gall bladder gave negative results. The anaerobic culture from the pancreas showed no growth after an incubation of seventy-two hours. The aerobic agar-agar plate from the pancreas contained at the end of twenty-four hours a single superficial colony of a pigment forming coccus whose cultural characters indicated tliat it was a contamination from the air. The streptococcus pyogenes and the staphylococcus epidermidis albus were isolated from the peritoneal cavity. Tlie colon bacillus was present in cultures from the liver and kidney.

Anatomiral diagnosis. — Cholelithiasis; calculus impacted in the diverticulum of Vater partially filling it and occluding its duodenal orifice. Aeule hemorrhagic pancreatitis; disseminated abdominal fat necrosis. Partial thrombosis of the splenic vein; embolism and thrombosis of branches of the portal vein.

The preceding autopsy has disclosed a condition which explains, I believe, the pathogenesis of those cases of acute hemorrhagic and gangrenous pancreatitis which are associated with gall stones. The diverticulum of Vater was 10 mm. in length. Lodged at its apex, blocking its duodenal orifice, was a small calculus only 3 mm. in diameter, but too small to pass the narrow opening. Though it occluded the duodenal orifice of the diverticulum it was so small that the orifices of the common bile duct and pancreatic duct were unobstructed. The two ducts were therefore, converted into a continuous closed channel from which it was not possible for either bile or pancreatic juice to escape.

On dissecting the pancreatic duct where it passed through the unchanged parenchyma in contact with the duodenum it was found, like the bile duct, to be stained bright green with bile. Where, as in this case, the two ducts become a closed channel, the entrance of bile into the pancreas or of pancreatic juice into the bile passages would depend upon the relative pressure in the two ducts. The pressure at which bile and


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paneroatic juice are secreted being small, any slight difference tliat might exist would be overcome by the gall Ijladder, a ijiuscular organ Avhicli at intervals forces bile in considerable quantity along the common duct.

A small calculus only partially tilling the ampulla of Vater can convert the two duets into a continuous channel, while a larger stone might simultaneously oTistruet the duodenal orifice of the diverticulum and the orifices of the two ducts wliicli enter it, thus damming liack bile and pancreatic juice upon their respective glands. In the present case, as previously mentioned, the diverticulum measured 10 mm. in length, the calculus 3 mm. in diameter. In many cases of hemorrhagic and gangrenous pancreatitis gall stones found in the gall bladder and bile passages at autopsy have been small and are often described as pea-sized. This statement is made in the reports of Pay,' Cutler,' Ivennan,° Simpson," Chiari " (two cases), Smith," Ehrich," Fraenkel," Korte," Morian,'" Eolieston," Grawitz," Opie,'° Bryant =° and Lund" (three cases).

Anatomical peculiarities of the diverticulum of Vater miglit favor or prevent' the conversion of the two ducts into a closed channel. The description of the ampulla given by Sappey,™ Testut," Henle'* and Quain '° does not differ materially. It may be described as a somewhat conical cavity into whose base open the two ducts; the apex situated at the summit of the diverticulum is their common duodenal orifice. Its length varies from 6 to 7 mm. according to Testut, from 7 to 8 mm. according to Sappey. Occasionally the two ducts have no common channel, but open by separate orifices upon the summit of the bile papilla. Claude Bernard '" described a variety of termination which has since been observed. The bile duct is prolonged as far as the mucosa of the duodenum, upon which it opens by a circular orifice. The terminal part of the pancreatic duct embraces the bile duct like a gutter and its. orifice has the outline of a crescent. Where the ampulla is very short or the two duets open separately into the duodenum it is evident that an impacted calculus could not render continuous the lumina of the two ducts.


'Day. Boston Med. ;iiul Surg. Jour., ISOi, cxxvii, p. .563.

Cutler. Ibid., 1S95, cxx.xii, p. 354. "Kenn.in. Brit. Med. Jour., 1806, ii, p. 1443. '"Simpson. Ediuburiili Med. Jour., 1897, ii, p. 24.5. " C'liiari. Wiener Med. Wocliensch., lS7(i, xxvi, p. 3iU ; Ibid., 1880, XXX, pp. 139, 164.

I'Smitli. Brit. .Med. Jour., 1897, ii, p. 468.

"Elirich. Beitrii^e z. lilin. Cbir., 1S98, xx, p. 316.

" Fraenkel. Miiuch. med. Wochenscli., 1896, xliii, pp. 813, 844.

isRorte. Arcli. f. klin. Cliir., 1894, xlviii, p. 721.

".Morian. .Miinch. med. Wochenscli., 1899, Ixvi, p. 348.

" Ilolleston. Trans. Path. Soc. of London, 1893, xliv, p. 71.

'«Grawitz. Miincli. med. Wochensch., 1899, xlvii, p. 813.

lii in 81 x,„. ,.if

■^■Sappey. Traite d'anatomie descriptive. Paris, 1889. '■'Testut. Traite d'anatomie humaine. Paris, 1894. =* Ilenle. Handbuch der Systematischen Anatomic des Mcnsclien. Braunschweig, 1873.

■'■Quain. Elements of Anatomy. London, 1896. '5 Quoted by Sappey.


I have recently examined the diverticulum of Vater in a small number of cases available. In three specimens (Nos. 3, 11 and 13) the ducts opened into the intestine by separate orifices. The following figures represent the length of the ampulla in these cases:


5 mm.


No.


1

2


.... 5 mm.

(; "



3


... "



4


4 "



5


.... 5 '*



6


. . . . 7 "



7 . . . .


... 10 "



8


.... 7 "



9


... .5.5"


Jo. 10 ...


3.5


" U



" 13...


6.5


" 13


...


" 14 . . .


. ..55


" 15


1.5


" 1()


1


" 17


11


No. G is from the case previously reported, No. 7 the one described in the present article. The figures are cited to show that the length of the so-called diverticulum varies considerably.

Another anatomical factor of considerable importance is the size of the duodenal orifice of the ampulla. Ilyrtl " states that this opening is narrower than the lumen of the gall duct at any point or is at least less distensible so that gall stones often remain here im]iacted. In the autopsy describetl the opening measured only 1 mm. in diameter. In most instances it measured 2 to 2.5 mm.; in specimen No. 9 the diameter was 4 mm.

EXPEHIMENTAL StUDT.

Hemorrhagic pancreatitis has been produced experimentally by the injection of a variety of irritating substances into the iiancreas, but no attempt has been made to reproduce the lesion by the use of bile.

Thiroloix "' injected several drops of deliquescent chloride of zinc into the duct of Wirsung in a dog. Death occurred suddenly after a short interval and the pancreas was represented by what appeared to be a blackish clot. Hlava " injected artificial gastric juice into the pancreatic duct. This fluid, containing hydrochloric acid in the proportion of 1 to 1000, caused death in three days; the pancreas was hypersemic and in the fat of the omentum and of the mesentery were numerous foci of necroses. Death on the tenth day followed the injection of 5 cc. of artificial gastric juice with hydrochloric acid 4 to 1000; the pancreas was the seat of hemorrhagic infiltration and the omentum and mesentery contained foci of fat necrosis. He suggests that in human cases hyperacid gastric juice may be forced by antiperistaltic action of the intestine into the pancreatic duct, thus causing the condition. Hlava has produced a hemorrhagic lesion of the gland Iiy injecting cultures of the bacillus coli communis, lincilliis lactis aerogenes, and bacillus capsulatus of Friedliiuder, but thinks that the change is the result of the acid products of these organisms.


"riyrtl. ITandbuch der Topographischcn Anatomic. Vicuna, 1882. '"Thiroloix. Quoted by Carnot (see below). "Illava. Quoted by Flexner (see below).


186


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


Oser '" records the injection of 4 cc. ol ^'u normal sulphuric acid solution into the pancreatic duct of a dog. Deatli followed in twenty hours. In the duodenal part of the gland was a hemorrhagic area the size of a pea where the tissue was destroyed and its structure no louger recognizable. By tlie injection of tiie fi'rment, papaine (0.2 grnis. in 30 cc. of water), inio |]ie duel of a ilog, C'arnot '" caused the deatli of the animal in twenty-five hoiirs; the pancreas was every wlierc inllltrated with blood but there was no necrosis of fat. Smaller doses did not produce hemorrhagic lesions. The same wi'ilcr pi'odueed hemorrlnxgic pancreatitis by the injci-lidii 1)1' the diphtheria toxinc into the pancreatic duct of a rabbit. A suspension of the bacillus coli connnunis (12 cc.) caused a similar lesion fatal in twenty-four hours. Subsequent injections of the same organism caused inllanimatory rliaiigcs wilbnut hemorrhage.

More varied ami successful experiments have been performed by Dr. Klexner^" in this laboratory. In ten experiments pei'l'iirnied ujiim ddgs bydnu-hloric acid varying in strength in dilfcrent instances from 0.5 to 2 per cent, and in amount from 3 to 8 ec, was injected into the pancreatic dui't. In six instances there resulted hemorrhagic inflammation of the gland, accompanied in five by focal fat lu'croses. In three of these cases death followed the operation within twenty-four boni-s; in [wo the animals wei'c killed. In tlie remaining experiments purulent or chronic inteistitial inflammaticni resulted. Hemorrhagic lesioms were produced in two dogs liy the use of nitric acid (1 cc. of a 2 per cent solution and 5 cc. of a 1 per cent solution); in one, by the use of chromic acid (8 cc. of a 1 per cent solution). In a second series of experiments sodium hydroxide solution (21) to .5 cc. of solutions varying in strength from 1 per cent to 2 per cent) was employed. Hemorrhagic lesions resulted in three cases and were accompanied by fat necrosis in at least two. Suspensicnis of bacteria were used in a third series, llenmrrhagic inflammation was caused liy the bacillus pyoej^aneus and in three experiments by the bacillus diphtheria' but was unaccompanied by definite fat necrosis. In two ex|ieriinents the lesion followed the injection of 5 cc. of a 2 [ler cent solution of formalin into the duct and was associated with fat necrosis.

The experiments cited show that a variety of substances injected into the duct of the pancreas cause hemorrliagic inflannnation. How far they can he used to explain the pathogenesis of human cases is doubtful. The suggestion of Illava that gastric juice may be driven by antiperistaltic action of the intestine into the duets is not supported by any evidence. The relation of hemorrhagic pancreatitis to bacterial invasion from the intestine has not been demonstrated. The condition observed in the autopsy described has suggested a mechanism by wliich an irritating substance can make its way into


3" Oser. Die Erlii-aukuugeu des Panlireas. Nntliuagel's Spec. I'ntli. u. Ther., xviii, ii, p. 2S6. Vienna, 1S'.)S.

3' Carnot. Paris Tliesis, 189S.

■'■ Flexncr. Contrilmtiiius tn the Science of Medicine, Dedicated to Wm. H. Welcli, M. D., p. 74;). Baltimore, I'.IOO.


the organ. Can the hemorrhagic inflammation observed in human cases and produced in animals by means of various irritants be reproduced by the injection of bile into the pancreatic duct?

In the following experiments the duodenum of dogs was opened for a distance of several centimetres opposite the larger pancreatic duet. Tlic blunt pointed nozzle of a syringe was inserted into the orifice of the duct and bile obtained from the same or from a second dog was injected into the organ. The ojierations were performed with the usual antiseptic precautions and the duodenal wound was closed by submucous nuittrcss sutures. I desire to express my thanks to Mr. Bassett, Mr. Haskell and Mr. W. Marshall for assistance in the performance of these operaticuis.

Experiment 1. — Into the larger pancreatic duct was injected ■") cc. of bile obtained from a second dog. The animal was killed seven days later. The peritoiu'al cavity contains a small anu)unt of bloody Hnid and the surface is injected. 1'lie large and several loops of the small intestine are firndy adherent to the splenic arm ol' the pancreas, and on separating them are exposed pockets containing very thick viscid fluid ol' dull red C(dor. The walls of these pockets have in places the opaque white aiipearance of necrotic fat. The splenic ]iart of the gland and the duodenal part, above the duodenal orifice of the main duet, is firm in consistence and both ujion the surface and on section shows a mottling of opaque yellowish-white areas se])ai'ated by dec]) hemorrhagic red. Over a considerable area at the junction of the duodenal and splenic parts of the gland the tissue is almost uniformly grayish-yellow and is in places softened and disintegrated. Cultures and coverslips from the peritoneal cavity and from the substance of the pancreas contain no bacteria. Microscopic examination of the splenic and duodenal parts of the gland show that wide areas of parenchyma including entire groups of lobules are necrotic and the -secreting cells, whicli have a homogeneous hyaline appearance and are stained deeply with eosin, contain no nuclei. At the margin of such areas red-blood corpuscles and polynuclear leucocytes are present in great number and fibrin is abundant. In places the bodies of the secreting cells have been converted into formless detritus mingled with red-hlood corpuscles ami leucocytes. The interstitial tissue may be implicated in the general necrosis but often it has undergone very active proliferation and has in small part replaced the disintegrated acini. Islands of intact parenchyma still persist in places and are surrounded by newly-formed fibrous tissue, containing red-blood corpuscles and polynuclear leucocytes.

U.rperimeiit 2. — Bile (.5 cc.) from a second dog was injected as before. The animal was killed at the end of five days. Lightly adherent to the part of the pancreas which is in eontact with the duodenum are several loops of small intestine. In the omental fat are several opaque white areas of fat necrosis, while near the splenic extremity are several inconsjiicnous foci of a similar nature. In the duodenal part of the gland in the neighborhood of the orifice of the larger duct for a distance of 3.5 cm., there is extensive henun'rhagic infil


Apeil-May-June, 1901. J


JOHNS HOPKINS HOSPITAL BULLETIN.


187


tratiou separating islands ui' paruuchyma. In places the gland substance is soft and of gray necrotic appearance. The .splenic part is lirm in consistence and at several points are areas of hemorrhagic inliltration. Microscopic examination of sections from the hemorrhagic duodenal part shows wide areas of necrosis implicating both lobular and interstitial tissue. The pareiiehynuUous cells are hjaliue and without nuclei. Copious hemorrhage has taken place into these areas and at the margin of intact tissue polynuclear leucocytes an; numerous. I'^ibrin is abundant in the necrotic interlobular tissue. Where widespread destruction has not occurred there has lieen active proliferation of interstitial tissue replacing in part destroyed parenehyina and containing numerous red blood corpuscles and polynuclear leucocytes. The remaining acini are often separated by newly-formed interstitial tissue and there is the appearance of advanced chronic inhamniation. In the splenic part of the gland foci of necrosis with hemorrhage occur and in small scattered areas there is newlyformed connective tissue.

Experiinenl 2. — After opening the duodenum o cc. of biK^ obtained from a second dog was injected into the pancreatic duct. Death followed within twenty hours. The peritoneal cavity contains several cubic centimetres of bloody Muid anil the peritoneal surface has an irregularly distributed, deep red injection. The entire omentum is studded with conspicuous oi)aque white areas of fat necrosis, usually round, 1 to 1.5 mm. in diameter, and surrounded by a zone of injection. They are most abundant in the neighborhood of the s])leen, where superlicially and on section they occupy about one-half the exposed surface. In the mesentery of the duodenum near the pancreas they are numerous, but in the remainder of the mesentery of both large and small intestine they are sparcely scattered. Similar foci are present in the retroperitoneal fat and in the properitoneal fat below the diaphragTii. The splenic arm and the upper half of the attached duodenal part of the pancreas are swollen and osdematous in appearance and the lobulations are separated by tissue iidiltrated with blood. The cut surface has a mottled dull red and gray color, the interstitial tissue being hemorrhagic, wjiile minute heaiorrhages wrv. in places seen within the lobular substance. The left lung is the seat of a mucopurulent bronchitis. A culture made from the peritoneal cavity remained sterile. A short bacillus was grown from the pancreas. Microscopical examination shows that the dull red areas of the ])ancreas represent foci of necrosis where the parenchyinMti}Us cells stain only with eosin and no Imigi'i contain nuclei. The blood-vessels hero are widely dilated and abundant hemorrhage has frequently taken place. Polynuclear leucocytes are present but are not very numerous. Such an area of necrosis and hemorrhage is at times limited to the central part of a lobule group, while the acini furtbeiU-inn the central duct are intact. The interstitial tissue particularly of tlie duodenal part of the ghiud has an (edematous appearance and contains red blood corpuscles, polynuclear leucocytes and fibrin.

Experimenl J/. — iiy means of a sliai-p pointed needle 3 ec.


of bile was withdiawu from the gall bladder and injected into the larger pancreatic duct. The animal was killed at the end of seven days. Upon the surface of the pancreas where it is in contact with the duodenum are a few sparcely scattered opaque white areas of small size. In the omentum near tlie gland are a few suuilar foci of necrosis. The pancreas is normal in consistence aiitl no change is noted macrosco2jicall3^ Microscopic examination sliows the interstitial tissue of the splenic and duodeual parts of the gland modeiately iufiltrateil in iilaces with blood corpuscles, while here and there it is distended and has an oedematous appearance. The pareneliyma is normal in tlm sections examined.

ExiJCiiinenL 5. — The operation previously described was repeated and 2.5 cc. of bile was withdrawn from the gall bladder and after opening the duodenum injected into the larger pancreatic duct. The dog was killed at the end of four days. The pancreas which is not adlierent to the adjacent structures is hrm in consistence and has throughout a reddish-gray color, but is nowhere hemorrhagic. (Ju the surface of the duodenal part in contact witii the duodenum are sparcely scattered opaque white areas of fat necrosis. Microscopic examination of a section from thi- duodenal part of the gland shows that newly-formed celhdar eonnecti\e tissue has in a small area replaced the glandular elements. I'roliferation of cells has occurred in the adjacent interlobular tissue which contains in abundance red" blood corpuscles, polynuclear leucocytes and fibrin.

Should bile enter the pancreas after occlusion of the distal end of the diverticulum of Vater, its only opportunity for escape would be by way of the lesser pancreatic duct. In order to reproduce this condition, in the following experiments the duodenum \vas not opened, but the duet was exposed wdiere it approaches the intestine, ligated close to the' duodenum and partially cut across. JJy means of a syringe with a blunt nozzle, bile was injected into the distal end of the duct which was then ligated.

Experimenl 6. — Into the larger duct was injected 5 cc. of bile obtained by puncture from the dog's gall bladder. The animal died twenty-four hours later. The peritoneal cavity contains no excess of tluid. Opaque white areas of fat necrosis are numerous upon the surface of the duodenal part of the pancreas and in the immediately adjacent fat of the duodenal mesentery. Similar foci are present in both layers of the )nesentery near the stomach and pancreas and in the fat in contact with the splenic part of the gland. The interstitial tissue of the duodenal part over an area near the orifice of the larger duct, 2.5 cm. in width, shows deep red hemorrhagic infiltration. The parenchyma throughout the gland is mottled, .small dull red areas alternating with more normal gray yellow gland substance. This hemorrhagic appearance of the parenchyma is most marked in the duodenal part of the gland wdicre there are homogeneous dull red areas of considerable extent. Both lungs contain extensive deep red areas which are feirly firm in consistence and exude very abundant frothy serum. Microscopic examination of all parts


188


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


of the pancreas shows the presence of numerous foci of necrosis. The ghind cells have assumed a hyaline appearance and have lost their nuclei. The blood vessels in these areas are widely distended and at times there is abundant extravasation of red blood corpuscles. Polynuclear leucocytes in moderate number are seen between the necrotic cells. The interlobular tissue is in many places much distended, containing red blood corpuscles, poljmuclear leucocytes and fibrin.

Experiment 7.- — The operation already described was repeated and 3.7 cc. of bile obtained from the gall bladder of the same dog was injected into the larger duct. The animal was killed three days later. Upon the surface of that part of the pancreas which is in contact with the duodenum and in the fat immediately adjacent to the splenic part are a few opaque areas of necrosis. Tlie pancreas is very firm throughout. On section the glandular lobules are found to be separated by septa of interstitial tissue which are firmer and thicker than usual and near the termination of the larger duct infiltrated with blood. In the duodenal and splenic parts of the gland microscopic examination demonstrates within the lobular tissue numerous small areas where newlyformed, very cellular interstitial tissue replaces groups of acini. The interlobular tissue is infiltrated with red blood corpuscles and often contains in great abundance polynuclear leucocytes and fibrin.

SYNOPSIS OF EXPERIMENTS.


I. — Duodenum Opened and Duct Injected.


Amount Mode of bile. of death.


Pancreas.


No. 1. . . .5tc.

No. 3 5cc.

No. 3 5cc.

No. 4 Src.


Killed in Hemorrhagic iuflamma 7 days. tion and sclerosis.

Killed in Hemorrhagic inflamma 5 days. tion and sclerosis.

Died in Hemorrhagic inllamma 30 hours. tion.

Killed in Slight hemorrhagic


Fat.

Eat necrosis near pancreas.

Fat necrosis.

Extensive

fat necrosis.

Slight

fat necrosis.


J, > o t;.. Killed in Slight hemorrhagic in- Slight "■ ■ 4 days. tiltration and sclerosis. fat necrosis.


No. 6.


. 5fc.


II. — Duct Opened, Injected and Ligated. Died in Hemorrhagic iullamma


24 hours.


tion.


^Fat necrosis. Slight


„ r. o 7,. Killed in Hemorrhagic intlamma ■ ' "' 3 days. tion and sclerosis. fat necrosis.

The injection of 5 cc. of bile into the pancreatic duct caused hemorrhagic inflammation of the gland in four dogs, two of which died within twenty-four hours after the operation. Death did not follow the use of smaller amounts and the changes produced in the organ were less wide spread and severe. In every case necrosis of the adjacent fat accompanied the lesion of the pancreas, and in the two instances in which death occurred spontaneously foci of necrosis were abundant and disseminated. In Experiment No. 1, though the entire splenic arm of the gland was the seat of an intense inflammatory reaction, eoverslips and cultures demonstrated the absence of bacteria. The presence of bacteria in the pancreas of dog No. 2, which died twenty hours after the


operation, is not surprising since the injection was made through the duodenal orifice of the duct.

Microscopic examination confirmed the diagnosis of hemorrhagic pancreatitis and demonstrated the identity of the experimental lesions with that which occurs in human cases. The injected bile first causes necrosis of the parenchymatous cells with which it comes into contact. They loose their nuclei and their protoplasm assumes a homogeneous hyaline appearance and stains deeply with eosin. The injurious action of the irritant upon the blood-vessels is manifested by the occurrence of hemorrhage into these necrotic areas. An inflammatory reaction now ensues and is characterized by the accumulation of polynuclear leucocytes and fibrin in the interstitial tissue and in the necrotic parenchyma. Tlie necrotic material undergoes disintegration and a rapid new growth of interstitial fibrous tissue in part or wholly replaces it. Where death docs not rapidly follow the primary effects of the operation opportunity is given for the occurrence of secondary changes in the gland. The experimental lesion is not in all cases so extensive as that recorded in the accompanying autopsy report. In these experiments a single injecy tion of bile is made, while in the human case bile is repeatedly poured into the organ.

Conclusions.

(1) A small gall stone impacted in the diverticulum of Vater may occlude the common orifice of the bile duct and duct of Wirsung and convert tliem into a continuous closed channel. Bile enters the pancreas by way of tlie pancreatic duct and the pancreas becomes the seat of inflammatory changes characterized by necrosis of the parenchymatous cells, hemorrhage and the accumulation of inflammatory products. Anatomical peculiarities of the diverticulum of Vater do not permit this sequence of events in all individuals.

(2) Injection of bile into the pancreatic duct of dogs causes a necrotizing hemorrhagic inflammation of the pancreas resembling tlie human lesion, and like it accompanied by fat necrosis. Necrosis of the parenchymatous cel