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[[The Johns Hopkins Medical Journal|The Johns Hopkins Hospital Bulletin]]
 
[[The Johns Hopkins Medical Journal|The Johns Hopkins Hospital Bulletin]]
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BULLETIN OF THE JOHNS HOPKINS HOSPITAL.
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Vol. Xll. - No. 118.
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BALTIMORE. JANUARY. 1901.
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==Contents - January==
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* The Removal of Pelvic Inflammatory Masses by the Abdomen after Bisection of the Uterus. By Howard A. Kelly, M. D., . . 1
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* Abstract. The Bacteriology of Cystitis, Pyelitis and Pyelonephritis in Women. By Thomas R. Buown, M. D., 4
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* The Intrinsic Blood- Vessels of the Kidney and their Signirtcauce in Nephrotomy. By Max Brodel, 10
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* Notes on jiC.obic Spore-Bearing Bacilli. By \V. W. Foud, M. D., r^.t.R., 13
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* Summaries or Titles of Papers by Members of the Hospital and Medical School Staff Appearing Elsewhere than in the Bulletin, 16
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* Proceedings of Societies:
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The Johns Hopkins Hospital Medical Society, 17
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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
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[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].
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Notes and News, 38
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Notes on New Books, 29
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Books Received, 30
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THE REMOVAL OF PELVIC INFLAMMATORY MASSES BY THE ABDOMEN AFTER
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BISECTION OF THE UTERUS.^
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By Howard A. Kelly, M. D.
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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.
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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
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■ An address delivered before The Southern Surg. & Gyn. Assoc, Atlanta, Ga., November 13, 1900.
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sible, as by doing this we conserve the function of menstruation as well as that of internal secretion of the ovary.
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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.
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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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.
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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.
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1 controls the left ovarian vessels.
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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.
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4 represents the division of the cervix exposing the right uterine vessels controlled by n.
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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.
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6 is the ligature on the right round ligament and 7 that on the right ovarian vessels.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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,
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE I.
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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.
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Ligatures may be placed on tlie ovarian vessels as shown before cuucleatinir the uterine tubes .and the ovaries, when the vessels are accessible.
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'ecMi^'r/ce
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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.
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rfi
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE II.
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Fig. .5. — After freeiuy; the cer\ix directiou from below up.
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from its vaglniil end it is held up and the bisettiun cuuiijlrtnl as shown here, iu a
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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.
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January, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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I have had abundant opportunity to demonstrate the practical value of this method of treatment in my clinic this year.
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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.
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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.
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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.
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Another patient in my private hospital had tubercular disease of both tubes (S., April, 1900), which was extirpated with bisection of the uterus.
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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.
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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.
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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
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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vessels in an indiscriminate fashion the nreter may be easily included in the clamp.
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I suppose, too, that it is easily possible with sufficient carelessness to cut a hole in the bladder.
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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.
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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:
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1. Additional space for handling adherent adnexte, afforded by the removal of the uterus.
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2. Great increase in facility for dealing with intestinal complications.
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3. Better access by new avenues from below and in front to adherent lateral structures.
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4. Elevation of structures to or above pelvic brim or even out into the abdomen, bringing them within easy reach of manipulation and dissection.
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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.
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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.
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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.
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I have found since writing this that a similar plan of operating has been advocated by J. L. Faure of Paris.
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ABSTRACT.'
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THE BACTERIOLOGY OF CYSTITIS, PYELITIS AND PYELONEPHRITIS IN WOMEN.
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By Thomas E. Brown, M. D., Assistant Physician The Johns Hopkins Hospital Dispensarij.
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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.
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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.
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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
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I The paper in full will appe.<ir in Volume. X, The Johns Hopkins Hospital Reports.
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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.
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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.
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The complete article will be subdivided into the following sections: I. The method of obtaining the urine aseptically;
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II. The chemical and microscopical examination of the urine;
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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
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January, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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5
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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.
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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).
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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.
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I. The Method of Obtaining the Urine Aseptically FROM Bladder and Kidney.
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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
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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.
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II. The Chemical and Microscopical Study of the Urine.
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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.
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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.
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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.
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6
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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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.
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III. The Bacteriological Study of the Ueine.
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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.
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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.
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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.
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INFECTIOXS of THE BLADDER.
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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.
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IV. Cases of Acute Cystitis.
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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.
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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
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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
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January, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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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.
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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.
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V. Cases of Chronic Cystitis (non-tuberculous).
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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.
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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.
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VI. Tuberculous Cystitis.
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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
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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.
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VII. Cases avitii Symptoms of Cystitis bttt with no Infection.
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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.
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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.
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pyelitis and pyelonephritis.
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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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8
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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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.
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VIII. Acute Pyelitis and Pyelonepheitis.
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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.
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IX. Chronic Pyelitis and Pyelonepheitis
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(non-tuberculous) .
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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.
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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.
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X. The Cases of Tuberculous Pyelitis and Pyelonephritis.
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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
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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.
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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.
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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.
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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.
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Discussion.
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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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January, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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9
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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.
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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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10
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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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.
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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.
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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
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tered throughout the kidney. The bladder mucosa seemed entirely healthy.
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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.
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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.
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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.
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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.
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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.
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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.
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THE INTRINSIC BLOODVESSELS OF THE KIDNEY AND THEIR SIGNIFICANCE
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IN NEPHROTOMY.
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By Max Bbodel.
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[PRELIMINARY COMMUNICATION.!]
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In view of the enormous number of investigations of the different structures of the kidney recorded in the literature
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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.
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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
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jANtlARY, 1901.]
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JOHNS:: HOPKINS HOSPITAL BULLETIN.
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11
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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.
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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.
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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.
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The Pelvis of the Kidney. — From a surgical standpoint all forms of pelves may be classified under two main groups.
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(1) True pelves with major and minor calices.
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(2) Divided pelves, where there is no free communication possible between all of the calices inside of the kidney.
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(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).
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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.
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p i! I employed Schieferdecker's corrosion-method, sliglitly modified by
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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.
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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.
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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.
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(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.
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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).
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Fig. 3 B demonstrates this in a schematic way. The sec
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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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12
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. lis.
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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'.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.
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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
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE III.
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o
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-o
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rt
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QJ
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P
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>
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 +
CO
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 +
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o
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 +
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a
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c3
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CM
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S
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OJ
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Q
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?
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05
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1=1
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if s
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<
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c 2 '*^
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_jy.n/w iv^'
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-3 «J b/; .
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S :3 ■= S 5 1-J vi 3J <aJ —
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ft. -p ,a 15 M o
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3 s
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE IV.
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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.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE V.
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Kui. ;;.— TliL- rc-inil iirtLTV :ni(l tlit- ilisti ibiitioii i>f its tiiMiiclies ill relation to tlic pelvis.
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.\. 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.
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y> o s t
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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.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE VI.
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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.
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Fig. 5 Variation of the median branch. Tliis brancli may be larsrer than usual and arise separately from the main artery at
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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.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE VII.
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Fig. 6. The renal vein and the relation of its branches to
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the pelvis of the kidney.
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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.
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B
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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
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE VIII.
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\;>^
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^
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THE JOHNS HOPKINS HOSPITAL BULLETIN. JANUARY. 1901.
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PLATE IX.
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-*-. ■ .^
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CNI
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C^
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"^
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\
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"'7 JJW"* * ... "^
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-i
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i.y::MH
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oo
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-;',v<!*t^
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<r'
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EC —
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CO -—
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^ — o ^ 72 i- ?; jj
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O) 5 U "" T*
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■^ ii s ^
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^H ^ o - C
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.2 = ^ < ^
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33 2 -^ <: 23 o
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THE JOHNS HOPKINS HOSPITAL BULLETIN, JANUARY, 1901.
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PLATE X.
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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.
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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.
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(!«' Lateral convex border of kidney.
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bh' Position of lateral column of cortical substance containing the vessels.
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<rc' Best incision.
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B. (le Incorrect direction of ineisii>n. I'x Correct direction of incision.
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Fio. 11. — Imaginary transverse section through a kidney similar to Fig. !l B, showing manner of ])lac-ing the mattress sutur-e^.
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January, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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13
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vessels of the kidney (three-fourths nf the arteries and all of the veins) are found (see also Figs. 3 and 6).
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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.
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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.)
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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.
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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.
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I wish to add a few suggestions as to the incision itseli and also as to the subsequent suture.
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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.
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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.
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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.
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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.
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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.
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IV. The capsule is then closed in the usual manner (Fig. lid).
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NOTES ON AEROBIC SPORE-BEARING BACILLI.
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By W. W. Ford, M. D., D. P. H., Felloiv in Pathology, McGill University. Montreal.
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{From the Mnhnn Pathological Laboratonj.)
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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.
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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.
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14
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Under Group 1, pathogenic spore-bearing bacilli, have been included five different varieties:
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Bacillus 4 is a capsulated bacillus which bears some re
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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.
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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.
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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.
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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.
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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.
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
Bku
 +
 +
 +
IGV.
 +
 +
 +
 +
 +
 +
 +
Patho
 +
 +
 +
 +
 +
 +
 +
 +
Morphology.
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
GKMCITV.
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
CULTURAL FEATURES.
 +
 +
 +
 +
 +
 +
 +
lUOCHKMICAL FEATURE
 +
 +
 +
^^.
 +
 +
 +
"MICE.
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
Broth.
 +
 +
 +
Ag-av.
 +
 +
 +
Gelatin Plate.
 +
 +
 +
O
 +
 +
o
 +
 +
 +
Fermentation Tube.
 +
 +
 +
£
 +
 +
 +
-_^
 +
 +
 +
=•
 +
 +
 +
Liquefaction.
 +
 +
 +
Ga-s production.
 +
 +
 +
 +
 +
 +
 +
 +
 +
Milk.
 +
 +
 +
Ag-ar.
 +
 +
 +
3* O
 +
 +
 +
Typk.
 +
 +
 +
Name.
 +
 +
 +
Source.
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
C
 +
 +
 +
 +
I
 +
 +
 +
7i
 +
 +
 +
si
 +
 +
 +
 +
 +
£ o
 +
 +
-3
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
^
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
.i|
 +
 +
 +
 +
 +
 +
 +
S
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
U
 +
 +
 +
 +
 +
3 u
 +
 +
 +
«
 +
 +
K i
 +
 +
 +
^ 3
 +
 +
 +
ca 3
 +
 +
3 O
 +
 +
 +
 +
 +
 +
 +
 +
 +
3
 +
 +
If,
 +
 +
 +
boo
 +
 +
 +
o
 +
 +
 +
i
 +
 +
 +
,
 +
 +
 +
 +
 +
3
 +
 +
 +
i
 +
 +
 +
si
 +
 +
 +
'v.
 +
 +
 +
 +
 +
il
 +
 +
 +
 +
 +
<
 +
 +
 +
o o
 +
 +
 +
 +
 +
1
 +
 +
 +
3
 +
 +
 +
as
 +
 +
s
 +
 +
X
 +
 +
 +
g s
 +
 +
 +
i s
 +
 +
tr.
 +
 +
 +
5
 +
 +
 +
 +
 +
'a
 +
 +
B
 +
 +
 +
■a o
 +
 +
o
 +
 +
 +
t.a,
 +
 +
 +
3)
 +
 +
 +
 +
 +
£' 5
 +
 +
 +
 +
 +
= .3
 +
 +
o g
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
g
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
 +
 +
P
 +
 +
 +
f
 +
 +
'-'
 +
 +
 +
> +
 +
 +
 +
-t
 +
 +
o
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
o -1
 +
 +
-1
 +
 +
Q
 +
 +
 +
 +
 +
 +
>-)
 +
 +
 +
la
 +
 +
 +
r^
 +
 +
 +
<i
 +
 +
 +
O
 +
 +
 +
<
 +
 +
 +
o
 +
 +
 +
ti.
 +
 +
 +
f.
 +
 +
 +
"
 +
 +
 +
 +
 +
 +
Bacillus A.
 +
 +
 +
Liver of ) rabbit <j
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
n
 +
 +
 +
Bacillus B.
 +
 +
 +
Kidney of )
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
-t
 +
 +
+
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
-1
 +
 +
+
 +
 +
 +
-t
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
_
 +
 +
 +
 +
 +
 +
 +
 +
 +
-1
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
rabbit j
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
0) o
 +
 +
 +
Bacillus C.
 +
 +
 +
Kidney of ) rabbit f
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
-f
 +
 +
 +
-1
 +
 +
-1
 +
 +
+
 +
 +
 +
-1
 +
 +
-f
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
5 g: Bacillus D.
 +
 +
£•3 1
 +
 +
 +
Kidney of ( rabbit f
 +
 +
 +
+
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
4
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
-1
 +
 +
-1
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
-t
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
-t
 +
 +
^ Bacillus E.
 +
 +
 +
Pleural } exudate f
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
__
 +
 +
 +
_
 +
 +
 +
+
 +
 +
 +
-(
 +
 +
-1
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
-1
 +
 +
-1
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
_
 +
 +
 +
 +
 +
 +
-t
 +
 +
_
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
_
 +
 +
 +
_
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
'u
 +
 +
 +
B. Subtilis.
 +
 +
 +
 +
 +
4
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
+ —
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
a
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
_
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
?
 +
 +
 +
+
 +
 +
 +
?
 +
 +
 +
 +
 +
 +
 +
 +
y
 +
 +
 +
 +
 +
 +
" 2
 +
 +
 +
B. Mesenterieus.
 +
 +
 +
? I
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
+ 1 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
-t
 +
 +
-t
 +
 +
-1
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
+
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
II
 +
 +
OJ o
 +
 +
 +
Bacillus F.
 +
 +
 +
Liver of ) guinea-pig f
 +
 +
 +
-1
 +
 +
1 — 'n
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
_
 +
 +
 +
_
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
n
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
S5
 +
 +
p. =3 CO P.
 +
 +
 +
Bacillus G.
 +
 +
 +
Stomach ) of man j
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
^
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
+
 +
 +
 +
-1
 +
 +
 +
 +
+
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
 +
Z
 +
 +
 +
Bacillus H.
 +
 +
 +
Liver of |
 +
 +
cat f
 +
 +
 +
+
 +
 +
 +
+
 +
 +
 +
 +
 +
+
 +
 +
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4
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Note.— Tlie media hero employed were prepared according to the directions given in the 1897 report of the Committee of American Bacteriologists with the exception that the reactions have been rendered neutral to plieuol-phthalein. The plus and minus signs have also been used in the manner directed by this Committee.
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16
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 118.
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SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.
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Simon Flexnee, M. D. Nature and Distribution of the New Tissue in Cirrhosis of the Liver. — University Medical Magazine, November, 1900.
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Andrew H. Whiteidge, M. D. Eeport of a Case of Tetanus with Eeeovery. — Philadelphia Medical Journal, October 20, 1900.
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William W. Foed, M. D. Venous Thrombosis in Heart Disease. — Philadelphia Medical Journal, November 17, 1900.
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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.
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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.
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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.
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Adelaide Dutcher. Where the Dnnger Lies in Tuberculosis. — Philadelphia Medical Journal, December 1, 1900.
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William Osler, M. D. On the Study of Tubennilosis.— Philadelphia Medical Journal, December 1, 1900.
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J. Hall Pleasants, M. D. A Case of Acromegaly in a Negro Associated with a Low Grade oE Giantism. — Maryland Medical Journal, December, 1900.
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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.
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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.
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J. H. Mason Knox, Ph. D., M. D. Compression of the Ureters by Myomata Uteri. — The American Journal of Obstetrics, September and October, 1900.
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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.
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The cases are gathered in several groups according to the severity of the ureteral and renal involvement; thus:
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Group A. — Moderate ureteral involvement, 8 cases.
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Group B. — I'ronounced ureteral pressure, 5 cases.
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Group C. — Mechanical destruction of renal substance, 1 case. Group D. — Ureteral pressure with inflammation, associated with
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a. Chronic nephritis, 2 cases.
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6. Congenital cystic kidneys, 1 case.
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C. Pyogenic infection, 2 cases.
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d. Pyogenic infection, severe, '■> cases.
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e. Kidney, a pus sac, 3 cases.
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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.
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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:
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1. That some compression of the ureter is produced by a large proportion of all large myomatous uteri.
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2. The resulting liydroureter and hydronephrosis may continue for years and give rise to no discomfort to the patient.
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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.
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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.
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5. Exploratory incision is occa.sionally justified to establish a diagnosis.
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6. The ureters should be inspected whenever the abdomen is opened for the removal of the tumor.
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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.
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8. Such serious sequelae of ureteral compression as extreme hydronephrosis, pyelonephrosis, etc., should receive appropriate treatment.
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The references to the cases aud a table are appended.
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PROCEEDINGS OF SOCIETIES.
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Vol. Xll.-No. 119.
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BALTIMORE, FEBRUARY. !90l.
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==Contents - February==
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* Preliminary Note of a Case of Infection with Balautidium Coli (Stein). By Richard P. Strong, M. D., and W. E. Musgrave, M. D., 31
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* 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
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* Two Examples of Bence Jones' Albumosuria Associated with Multiple Myeloma. By Louis P. Hamburger, M. D., . . . 38
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* 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
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* Introductory Note to Drs. Durham and Myers's Report. By William H. Welch, M. D 4S
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* 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
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* Summaries or Titles of Papers by Members of tlie Hospital and Medical School Stall' Appearing Elsewhere than in the Bulletin, 4i)
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Notes on New Books, 50
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PRELIMINARY NOTE OF A CASE OF INFECTION WITH BALANTIDIUM COLI (STEIN).
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By' Eichakd p. Strong, M. D., Assistant Surgeon, U. S. A., Director of the Army Pathological Lahoralorij, Manila.
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AND
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W. E. Musgrave, M. D., Hospital Steward, U. S. A., Resident Pathologist to the First lieserve Hospital.
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(From the Army Falholoijkal Laboratory, Manila, P. I.)
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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.
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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.
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Malmsten,' in 1857, in Stockholm, first described the par
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' Malmsten: Infusorien als Intestinal-Thiere beim Menschen. Virchow's Archiv, Bd. sii, p. 302.
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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.
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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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32
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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.
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In 1862 Stein proposed the name Balantidinm eoli for the parasite.
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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.
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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.
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We wish to contribute another case to the literatiire of infection with this parasite.
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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.
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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
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'Mitter: Beitrag zur Kenntuiss des Balnnt. coli. Inaiig. Diss., Kiel 1801.
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^ De la Chapelle : Finska lak.-sallsk. liandl., Ilelsiugfors, 1S90; xxxviii, 1041.
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■• Opie : Twentieth Century Practice of Medicine, vol. six, 1900.
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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.
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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.
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Agar plate cultures from the heart, spleen, liver and kidneys were negative for organisms.
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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.
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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.
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HYPEREXTENSION AS AN ESSENTIAL IN THE CORRECTION OF THE DEFORMITY OF POTT'S DISEASE, WITH THE PRESENTATION OF ORIGINAL METHODS/
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By p. Tunstall Taylor, B. A., M. D., Surgeon to the Hospital for Crippled Children, Baltimore; Fellow of the American Orthopedic Association, etc.
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Any successful treatment of tuljcn-ular spondylitis must be based on a careful consideration of the anatomical, patho
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' Read, in part, at the Fourteenth Annual Meeting of the American Orthopedic Association, on May 13, 1900, Washington, D. C.
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logical and mechanical problems involved, and any method determined on must stand the test of clinical experience before acceptance.
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Let us first consider briefly some of the chief anatomical features of the spine from the standpoint of the mechanics
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Februaet, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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33
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in the causation and in the treatment of this tubercular osteitis of the vertebrje.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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'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.
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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.
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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.
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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.
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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.
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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.
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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
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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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34
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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.
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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.*
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Calot published a paper on similar operations in 1896.'
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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."
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Eedard in the same year published his method of mechanical traction in a prone position with anaesthesia and manual pressure on the boss."
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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).
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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.
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' Hadra, Trans. Amer. Ortbo. Assoc, vol. iv, 20.5.
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Cl)ipauU, Medicine Moderne, No. 20, Sixieme Ann^e.
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9 Calot, Trans. Acad. M^d., Paris, 1896.
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I" Goldtliwait, Trans. Amer. Ortlio. Assoc, vol. ir, 1S89.; Boston Med. and Surg. Jour., July 28, 1898.
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"Eedard, Archivlo di Orthopedia, 1898, Fasc. 2.
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'■Transactions, vol. xii, and N. Y. Med. Jour., May 12, 1900, 716.
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This year I wish to present two recimibent kyphotones which carry out the same mechanical principles of hyperextension.
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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.
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The pressure-rod, attachments for hands and head-sling are similar to the upright kyphotone (Figs. 10 and 11).
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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).
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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.
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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).
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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.
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(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.
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IS Boston Med. and Surff. Jour., June 14, 1900.
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Febkuary, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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35
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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.
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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.
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(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.
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(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).
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(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.
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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.
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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
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"Annals of Surgery, 1899, vol. xvii, 323.
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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.
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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).
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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.
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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.
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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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3G
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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being eliminated. Fatal and untoward results have been reported by Sherman," Jonnesco," Lorenz " and others.
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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.
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As to the comparative value of the three machines, the upright kyphotone finds more general application than the
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For conclusions as to these methods of correcting the deformity of Pott's Disease and applying plaster jackets, I would say:
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First. The jackets thus applied fix the spine in the most advantageous position for lessening the tendency for the production of deformity.
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Second. The rapidity and ease with which jackets may be applied.
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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.
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Fourth. It seems comfortable to the patient, as the
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S IE 1897 11"
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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
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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.
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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.
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•5 Pacific Record of Med. and Surg., October 1.5, 1898, 73. ■'Communication to Twelfth Internat. Congress of Med. " Deutsch med. Wochen., 1897, 556.
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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.
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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.
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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.
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THE JOHNS HOPKINS HOSPITAL BULLETIN. FEBRUARY. 1901.
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PLATE XI.
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Tiihcrcuhir ioflciiiin;.
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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.
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Fi(;. 2. — Diagram showing [\) Normal position of adjacent vertebrse.
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(B) Falling forward of the vertebral bodies in caries of the spine.
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(C) The aim of treatment of Pott's Disease by means of spinal extension in its true sense.
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. — The planes of the vertebral bodies.
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. — The line of the centre of gravity and of the superincumbent weiiibt.
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Fig. .<{. The oritriuiil )'laster jacket stool. is;i,"i
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THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1901.
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PLATE XII.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY. 1901
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PLATE XIII.
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Fig. 8. — A double pliotogfiiphic- cxposuri". Lower figure shows child (II. T. i iu sittinir |"isture.
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Upper tiijurc shows rhihl ill. T.I snspciuh-d liy lu';ul, with no ri-diu'tioii in the kypliosis.
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Fir., il. —Shows cliild (II. T. ) hyperc-xteiuhHl with obliterutiou of the kyphosis.
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Fio. 10. — Case (\V. W.) showiim- di'forinit\ . Kyphotoue sci'U on the ri^■ht.
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Kic. 11. — Case iW. W.) sreu lOi the hirue ri'cuinhent kyphotone.
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Fic. \2. — Case (B. H.) and small reninibcnt kyidiotun.-.
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Fig. 13. — Case (B. H.) showint;- complete (dditcration of the deformity.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1901.
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PLATE XiV.
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Fig. 14 — Case (C. N.) scolioti
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Fid. ifi. —Case (C. N.) sliowiiiy' correction effected on large recnmbent kyphotone anil maintained by a plaster jacket.
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Fiii. 17 — Conipton Riely's moditication, adjustable by set-screws to any pelvis. Arrows indieate imints where pressure is made.
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Ki
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o. I.-,._Case (C. N.) on large recumbent kyi>liotone.
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February, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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37
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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.
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EeCENT BlIiLIOGRAPHY ON PoTT's DISEASE.
 +
 +
Anders: Arch. f. Chir., 1898, Ivi, 703.
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Aue: Ann. Euss. Chir., St. Petersburg, 1898, H. 3, 472.
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 +
Babaeei: Eaceoglitore med. Forli.. 1897, xxiv, 25.
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Barragony y Bonet: Eev. de ther. med. chir., 1899, 3-12.
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 +
Banning: Interstate Med. Joiir., St. Louis, June, 1900.
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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.
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 +
Blondez: Ann. de la Soc. Beige de chir., Brussels, 1898, vi, 72.
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Bobrofl: Med. obozy., Moscow, 1897, 696.
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Bouquet: Eev. d'orthop., Paris, 1900, xi, 217-218.
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Bradford and Vose: Annals of Surgery, 1899, xvii, 223.
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Bradford: Med. Press and Circ, Lond., n. s., Ixix, 13G137; Eev. mens. mal. I'euf., Paris, 1900, xviii, 450-455.
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Bradford and Cotton : Bost., M. and S. J., 1900, cxliii, 12, 277-283.
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Braun: XXVII Congr. deutsch. Chir., 1898.
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Broca: Presse med., 1897, 213.
 +
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Brun: Ibid.
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 +
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.
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Carleton: Yale Med. Jour., New Haven, 1900, vi, 315322.
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 +
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.
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Czajkowski: Gaz. Kek. Warszawa, 1898, xviii, 64.
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D'Addosio: Puglia Med., Bari, 1898, vi, 116.
 +
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Delcroix: Presse med. Beige, Brussels, 1897, xlix.
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Dane: Pediatrics, K Y., 1900, x, 14-17.
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De Eothschild: Proges med., Paris, 1898, viii, 497.
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Ditman: Euss. Arch. Pathol. Klin., St. Petersburg, 1898, V, 207.
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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.
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 +
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.
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Gibney: Medical News, New York, 1898, lxxiii,_ 391; Transactions of the American Orthopedic Association, 1898, xi, 83; New York Medical Journal, 1898, Ixvii, 427.
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Golthwait: Transactions of the American Orthopedic Association, 1898, xi, 897.
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Guibal: Bull, et mem. Soc. Anat. de Paris, 1899, Ixxiv. 945-956.
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Greenwell: Fort Wayne Med. J.-Mag., 1899, 413-416.
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 +
Guyot and Oilier: La Gibbosite du mal de Pott, Paris, 1897.
 +
 +
Hallstrom: Duodecjmus; Haelsink, 1897, xiii, 344.
 +
 +
Haudek : Wien. med. Woch., 1899, xlix, 1930.
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 +
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.
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 +
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.
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Jeannel: Arch. prov. de chir., 1897, vi, 383.
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Joachimsthal : 70 Naturf. u. Aerzteversamml., Diisseldorf, 1898.
 +
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Jones: Liverpool Medico-Chirurgieal Journal, 1898, xviii, 154; British Medical Journal, 1897, ii, 336.
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 +
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.
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Kummell : Ibid.
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 +
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.
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Ligorio: E. Eiv. di Chir., Torino, 1899, 1, 65-69.
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38
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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Lorenz: Deutsch. med. Woch., 1897, 556; Zeitschr. f. orth. chir., 1897, v, 343; Twelfth luteruational Congress at Moscow.
 +
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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.
 +
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Meneiere: Med. mod., Paris, 1899, x, 313-316.
 +
 +
Meyer: Zeitschr. f. orth. Chir., 1898, vi, 201.
 +
 +
Miilot: These de Paris, 1898.
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 +
Monod: Bull, et mem. Acad, de med., Paris, 1897, xxxvii, 695; Gaz. des hop., Paris, 1897, Ixx, 656; Presse m6d., 1897, No. 57.
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 +
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.
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 +
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.
 +
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Williams: Lancet, London, 1898, i, 1352.
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Wolff: Berlin, klin. Woch., 1898, Nos. 7, 8.
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WiiUstien: Arch. f. klin. Chir., 1898, Ivii, 485; Centrbl. f. Chir., 1898, xxv, 705.
 +
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Young: Internat. Med. Mag., Sept., 1900.
 +
 +
Zenatski: Wratsch., St. Petersburg, 1897, xviii, 877.
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TWO EXAMPLES OF BENCE JONES' ALBUMOSURIA ASSOCIATED WITH MULTIPLE MYELOMA.^
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A PRELIMINARY REPORT.
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By Louis P. Hambuegek, M. D., Assistant in Medicine, Johns RopHns University.
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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.
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On the 13th of last month. Dr. Iglehart brought me a specimen of urine with the remark that it contained an
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' Deitnnstratiiin before the Johns Hopkins Hospital Medical Society, November 5, I'.IOO.
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February, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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39
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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10
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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.
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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.
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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.
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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.
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Some hyaline casts are present in the sedmient.
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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.
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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
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sVlrch. Arch., 1866, Bd. xxsvi, 8. 125. 3Deut. Arch. f. Kl. Med., 1869, Bd. v. S. 215.
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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.'
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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.
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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.
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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
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See Senator, Ueber Peptonurie, Deut. lied. Wochenscbr., 1S95, Bd.
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21, S. 317.
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sZeitschr. f. Biol., 1S83, Bd. xix, S. 1.59, 209; 1884, Bd. xx, S. 11. «Pbil. Trans. Royal Soc, 1848, Pt. 1, p. 55.
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Febkuakt, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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41
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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."
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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."
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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.
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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
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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.
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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.'"
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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.
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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.
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Askanazy's case of lymphatic leukemia " constitutes the second apparent exception.
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His patient was a man fifty-one years of age, who was ad
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'Med. Chlr. Trans., London, 18.50, vol. 3.3, p. 211.
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Loc. cit.
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sPrag. Med. Woclienschr., 1889, Bd. 14, 8. 33.
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'«Deut. Zeitschr. f. Chir., 1873, Bd. 3, S. 163.
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" VIII Congresso dl medicina interna, 1897, (Transactions).
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'■'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.
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"Loc. cit.
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"Deut. Arch. f. Kl. Med., 1900, Bd. 68, S. 34.
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42
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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.
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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.
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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.
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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.
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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
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" Verhand. d. Cong. f. inn. Med., 1900, S. 40R, et. spq.
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remissions in the intensity of the reaction, a fact noted by Matthes and likewise observed in the second case of our series.
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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."
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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.
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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.
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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.
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Bradshaw's patient voided a milky urine from time to time for a jenT previous to the onset of any localizing symptoms.
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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.
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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
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'5 Loc. eit.
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IS See Rosin, loc. cit.
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" Loc. cit.
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" Loc. cit.
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February, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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43
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neoplasms in the Cohnheim sense, inasmuch as they probably never metastasize.
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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.
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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.
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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:
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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.
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During the year 1880 paroxysms of intense pain, referred
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I'Loc. cit.
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20 See Hammer, Virch. Arch., 137, S. 300.
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'" Contributions to the Science of Med. dedicated to Dr. W. H. Welch. The Johns Hoplcins Press, Baltimore, 1900.
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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.
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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.
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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.
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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.
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 +
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
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44
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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."
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 +
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:
 +
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Discussion.
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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.
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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
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»3Berl. Kl. Wochenscbr., 1899, Bd. 36, S. 161.
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Febhuaey, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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45
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diagnose as l3aiipho-sarcoma, round-celled sarcoma, etc., will be found to be plasmomata.
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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
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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.
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Dk. Hamburger. — I know of no relation between the two conditions and of no literature on the subject.
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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.
 +
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Examination of Dr. Iglehart's patient now shows a slight but definite elevation over the ninth left rib in front.
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RErORT OF A CASE OF FULMINATING HEMORRHAGIC INFECTION DUE TO AN ORGANISM
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OF THE BACILLUS MUCOSUS CARSULATUS GROUP.
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By Gkorge Blumer, M. D., and Arthur T. Laird, M. D.
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(From the Bcmhr Hijijknic Laboratory, Alhaiitj, N. Y.)
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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.
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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.
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A. F., aged 20, a machinist.
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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.
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1 Howard : .Journal of Experimental Medicine, vol. iv. No. a, 1899.
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'Bordoni-Ua'reduzzi: Zeitsehrift fiir Hygiene, 1888, Hft. iii.
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3 Von Dungern: Centralblatt fiir Bakteriologie, Bd. xiv, No, 17, 1893.
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"Kolb: Arbeiten aus den Kaiserliche Gesundheitsamte, Bd. vii, 1891.
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5 Tizzoni and Giovanni: Ziegler's Beitriige, vi, p. 201, 1889.
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6 Babes: Archives de Medecine Expcrimentale, tome v, 1890.
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Past History. — The patient has always been unusually strong and athletic. His habits are excellent.
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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.
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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.
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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.
 +
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The autopsy was made six and a half hours after death in cool weather.
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The following notes are abstracted from the protocol:
 +
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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.
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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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46
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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The lungs show numerous subpleural hemorrhages with congestion, and a few elevated, finely granular, deep-red areas, suggesting fresh broncho-pneumonia.
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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.
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The liver is enlarged, soft, and markedly cloudy.
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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.
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The adrenals, bladder, prostate and pancreas are normal.
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The stomach shows a few submucous hemorrhages, but is otherwise normal.
 +
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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.
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The large intestine is normal.
 +
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The mesenteric glands are swollen, some of them being pale, others hemorrhagic.
 +
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The brain and cord could not be examined.
 +
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MiCEOscopic Examination.
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The heart-muscle shows uothiug beyond an excessive number of polymorphonuclear leucocytes in the vessels.
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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.
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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.
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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.
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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
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which contain many of them. No casts are seen in the tubules.
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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.
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 +
The changes in the mesenteric lymph glands are essentially the same as those in the lymphatic apparatus of the intestine.
 +
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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.
 +
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Cultures were made at the time of the autopsy from the heart's blood, lung, liver, spleen, bile and a mesenteric lymph gland.
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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:
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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.
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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.
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February, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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47
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No spore-formation is observed.
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Flagella are not present, and the organism seems to be non-motile.
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The organism grows best aerobically, but is also capable of growth under anaerobic conditions. It grows on media as follows :
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 +
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.
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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.
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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.
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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.
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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.
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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.
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Blood-serum. — The growth is similar to that on agar. There is no liquefaction of the medium.
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Indol-Formation. — The organism produces indol in dextrose free bouillon after 4 days at C. 37°.
 +
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Gas-Formation. — Several different tests were made with each medium. Gas noted after 72 hours at C. 37°.
 +
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In 1 per cent glucose bouillon, 45-60 per cent of gas.
 +
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H f
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In 1 per cent lactose bouillon, 45-55 per cent of gas.
 +
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H f
 +
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In 1 per cent saccharose bouillon, no gas is found as a rule. On one occasion a trace was noticed.
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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
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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.
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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.
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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.
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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.
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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:
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" 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."
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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
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'Fricke: Zeitscbrift fiir Hygiene, Bd. xxiii, 1896.
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48
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 119.
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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
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recorded ones. The various organisms of this group studied by Strong ° all produced gas in saccharose, as did the organisms recently studied by Howard."
 +
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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.
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8 Strong: Journal of the Boston Society of the Medical Sciences, vol. iii, ISnSI.
 +
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' Iloward: Journal of Experimental Medicine, vol. v, no. 2, 1300.
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INTRODUCTORY NOTE TO DRS. DURHAM AND MYERS'S REPORT.
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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.
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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.
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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.
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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!
 +
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WiLLi.vM H. Welch.
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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.
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 +
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.
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 +
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.
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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.
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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.
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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.
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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
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February, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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49
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reason of the difficulty of establishing growths on artificial media.
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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.
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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.
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8. Pure growths of these bacilli are not obtained in ordinary aerobic and anaerobic culture tubes.
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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
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vestigation into the necessary constitution of culture media for successful cultivation is in progress.
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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.
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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.
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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."
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Para, Brazil, Januarv 28, 1901.
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'We have found this sometimes useful in examining the blood of ague patients.
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SUMMARIES OR TITLES OF PAPERS BY MEMBERS OF THE HOSPITAL AND MEDICAL SCHOOL STAFF APPEARING ELSEWHERE THAN IN THE BULLETIN.
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Vol. XII - No. 120.
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BALTIMORE, MARCH, 1901.
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==Contents - March==
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* 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
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* 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
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* 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
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* Summaries or Titles of Papers by Members of the Hospital and Medical School Staff Appearing Elsewhere than in the Bulletin, 80
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Further Observatious on Epincidirin. By .John .J. Ahel, M. D., 80
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THE GENESIS OF CARCINOMA OF THE FALLOPIAN TUBE IN HYPERPLASTIC SALPINGITIS, WITH REPORT OF A CASE AND A TABLE OF TWENTY-ONE REPORTED CASES.
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By E. K. Le Count, M. D., Assistant Professor of ralhology, Rush Medical CoUege.
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{From t/ic Pul/iuldr/iral L'thiirndirij «/ Itnsh Medical College.)
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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
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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
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Ergebnissed. alls;. Path. ii. path. Anat., 18!).5, ii, p. 'i90, Wiesbaden.
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56
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 120.
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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.
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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).
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Another instance of lesions which represent transitions between hyperplasia and benign tumor is furnished by mul
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5 Ann. Siirs., 1893, xviii, p. S, Phil.
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3 Die allt;. Patliologie, etc., ii, p. 491, 1889, .Jena.
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■• Vorlesungeu iiber allg. Pathologie, p. 393, 1882, Berl.
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5L. c., p. 397.
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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.
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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).
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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.
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6 Lelirbueli der spec. path. Anatomie, i, p. 9.')7, 1S97, Berl. 1 Arch. f. path. Anat. (etc.), cli.K, p. 290, 1900, Berl.
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8 Grundriss der allg. Pathologie, p. 144, 1892, Leipzig.
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9 Lehrbuch der path. Anat., i, p. 180, 1890, Leipzig.
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10 L. c, p. 137.
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" Lehrbuch der path. Anat., ii, p. 4.'i0, 1894, Lcijizig.
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12 L. c, p. fil.5.
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i^Lehrbnch der spec, jiath. Anat., ii, p. .539, 1889, Berl.
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March, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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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.
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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."
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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.
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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
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!■' Deutsebes Arch. f. klin. Med., Iv, p. 429, 189.5, Leipzig.
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'» 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.
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i^Les polyadenomes du gros intestine. Rev. de Chir., xi.v, p. 405, 1899, Paris.
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1' Rev. de gynec. et de chir. abd., ii, p. 484, 1898, Paris.
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iSArch. f. path. Anat. (etc.), cliii, p. ISO, 1898, Berl.
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"L. c, p. 743.
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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.
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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.)
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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.
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To substantiate the view that the polypous growth occurs first and that the production of tumor follows, the following citations will suflHce:
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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:
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" 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.
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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
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■» Das CylindiTepithel-carciuom des Magens und des Diclvdarms, p. 261, 1890, Jena.
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"Berl. klin. Wchn?chr,, xxvii, p. 649, 1890.
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"L. c, p. 539.
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2' Cancer of the Uterus, etc., p. 3.55, 1900, N. T.
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"Beit. z. path. Anat. u. z. allg. Path., xxvi, p. 367, 1899, .Jena.
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58
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 130.
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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,
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« Arch. f. path. Anat. (etc.), Ixvi, p. 13!», ISTfi, Berl.
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ssArch. f. path. Anat. (etc.), cxiii p. 468, tSSS, "Berl,
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" Verhandl. d. deutsch. Gesellsrh, f. Chir., xxit, s. 340, ISfl.i, Berl.
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«» Cited by Stoerk.
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29 F. Bierhoff, The Medical News, Ixxvi, p. 810, 1!)00, I'hil.
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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.
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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
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'"Special Pathology and Therapy of the Diseases of Women, vol. ii, Diseases of the Fallopian Tubes and Ovaries (Russian), 1807, St. Petersburg-.
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" 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.
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Si La Gynecologie, iii, p. 389, 1898, Paris.
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Nouv. Archiv. d'Obstet. et de Gynec, vi, p. 11, 1891, Paris.
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s-" Johns Hopkins Hospital Bulletin, ix, p. 163, 1898.
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March, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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59
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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:
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" 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."
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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."
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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
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35 Bull. Soc. Anat. de Par., 1897, xi, n. s., p. ."ilS.
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^V. Macrez : Des Tumenrs papillaires de la Trompe deFallope, p. 61, 1899, Paris.
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3' Bull. Soe. Anat. de Par., 1893, vii, p. .50.5.
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38 Tr. Path. Soc, 1888, xxxlx, p. 300, London.
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39 J. akush. 1 jensk. boliez., xii, p. 29, 1898, St. Petersb. "Arch. f. Gyniikol., Iv, p. ."JIB, 1898, Berl.
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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."
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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
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•"tTber primiire Tubcncarcinom. Geburtshiilfe u. Gynakologie, ii, p. .337, 1895, Leipzig.
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«Tr. Obstet. Soc. (London), 1898, .xl, p. 303.
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" Die Krankheiten der Eileiter, A. Martin, p. 353, 1895. Berl.
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«Tr. Path. Soc. (London), 1880, xxxi, p. 174; Idem., 1883, xxxiii Supplementary Reports, p. 49.
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60
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 120.
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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.
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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).
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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
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<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.
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«Bolnitsch. gas. Botkina., Nos. 42-44, 1898.
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■"Collection of works in Obstetrics and Gynecology, dedicated to Prof. K. F. Slavyanski (Russian), p. 227, 1894, St. Petersburg.
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48 Ann. de Gyn^c. et d'Obst., 1894, xlii, p. 203, Paris.
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"Berl. kliii. Wcbuseli., 1898, xxxv, p. 5.54.
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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.
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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
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5»L. c, p. 447.
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51 L. 0.
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5- Centralbl. f. Gynak., xvi, p. 357, 1889.
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s'Ztsch. f. Geburtsh. u. Gyniik., 1889, xvi, p.
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"Doran Tr. Obstet. Soc, 1898, xl, p. 200.
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"•Arcliiv f. Gynak., 1897, liii, p. 183, Berl.
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■«Wien. klin. Wcbnscb., 1899, xii, p. 1230.
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564, Stuttg.
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March, 1901.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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61
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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.
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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."
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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.
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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
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"Meditsina, iii, p. 181, 1891, St. Petersb. "Wien. klin. Wohnsch., 1894, vii, p. 573. "L. c, ]i. 4.5.5.
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fiO j^
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r
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«'L. c, p. 300. «5L. c, p. llfi.
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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.°°
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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:
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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.
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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.
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Maceoscopical Appearance.
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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).
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«3Tlii3 case was briefly reported at the Cliieagi) Gynecoloijical Society, December 15, 1899, I)y Dr. Newmnii and myself.
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62
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JOHNS HOPKINS HOSPITAL BULLETIN.
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[No. 120.
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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.
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Microscopic Appeahance.
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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
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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.
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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
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THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH. 1901.
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PLATE XV.
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Fig. I. — Tubal carcinoma — anterior surface — natural size.
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a. — Accessory tube.
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Fig. 3. — Tubal carcinoma — posterior surface — natural size. (( Ovary.
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Fig. S — Tubal carcinoma sectioned longitudinally (three-fourths of natural size).
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(I. — Uterine end.
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b. — Muscular wall.
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c. — Necrotic tissue.
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<l. — Papillary growth of the liiiiug toward tlie lumen of the tube.
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THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH, 1901.
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PLATE XVI.
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fe.
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^V
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f
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"mm
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1
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.mm -.■.-.saJrl*??'
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W
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■w ■"
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C
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■li;.'"
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•/
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- J.
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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.
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■ _■ •%;.^v.>-.;, ...... ;,•
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Fiu. 11. — "Invertintc tyi>e " of [uoliferation. The epithelium between the papillary growtlis has proliferated outward toward the muscular wall.
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(/. — Necrotic tissue.
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h. — Stroma.
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<•. —Epithelium.
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il. — Masses of epitlndinni linin;; cavities that have not been opened in this section.
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- /
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M
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Fig. 5. — Intricate arranuemcnt of stroma and epitlielium in which il is ditlicuU to interpret the appearances without the study of serial sections.
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n. — Necrotic tissue.
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h. — Stroma.
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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.
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!(.— Diverticulum lilled with necrotic tissue.
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Ik — Beginning papillary ]troliferntion of eidthelinin into the diverticulum (cystl.
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c. — Muscular wall of tube — only a jiart of wiiii-h is shown.
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Makch, liioj.j
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JOHNS HOPKINS HOSPITAL BULLETIN.
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63
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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.
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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.
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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
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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.
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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
 +
 +
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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.]
 +
 +
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 +
JOHNS HOPKINS HOSPITAL BULLETIN.
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 +
 +
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65
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 +
 +
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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.]
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JOHNS HOPKINS HOSPITAL BULLETIN.
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67
 +
 +
 +
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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
 +
 +
 +